TresSugar

Three Common Penile Problems, Part III

DearSugar — Fri, 29 Aug 2008 13:00:00 -0700

You've learned about Hypospadias and Peyronie's disease and to close out this series, I'm going to talk about Balanitis. Balanitis is a fancy word for an inflammation on the head of the penis, and symptoms include redness or swelling, itching, rash, pain, and a foul-smelling discharge. Now that I've sparked your interest, click here to read more.

Balanitis is prevalent with uncircumcised men and usually comes to fruition when men have poor hygiene. If dead skin, sweat, debris, and bacteria isn't properly cleaned, it can collect under the foreskin and cause inflammation and dermatitis. While a good cleaning can cure Balanitis, oral antibiotics or antifungal medication may be required. Again, this is not a life-threatening problem, but it can be painful and irritating.

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Three Common Penile Problems, Part II

DearSugar — Thu, 28 Aug 2008 15:00:00 -0700

Yesterday you learned about Peyronie's disease, one of three common penile problems that some men have to deal with, but today I'm going to talk about Hypospadias. This condition is when the urinary meatus, the hole on the penis where urine and ejaculate pass, is abnormally positioned. It's usually just short of the tip of the penis but can be as extreme as being positioned underneath the penis or as far back as the scrotum. Hypospadias is actually fairly common, affecting approximately 1 in every 300 newborn boys (this condition is present at birth) so if you want to learn more about it, just read more.

The only way to treat this condition is to have surgery to reposition the urethral opening, and if need be, straighten out the penis. In most cases, the surgery is successful and results in normal or near-normal function and appearance with no future problems, although it is possible for a meatus to form under the penis where the new urinary channel was created, which can cause leakage. If that were to occur, another surgery would be necessary. Although this condition isn't life threatening, it can most definitely be an emotional burden.

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Three Common Penile Problems, Part I

DearSugar — Wed, 27 Aug 2008 09:00:00 -0700

We all know that men have a very serious connection with their penis, and just because it can be a source of great pleasure, according to AskMen.com, it can be a source of considerable anxiety as well. In this three-part series, I'm going to talk about the most common problems men face. To learn about the first one, Peyronie's disease, just read more.

Peyronie's disease is really just a fancy name for a crooked penis. While it can also present itself as a bump or thickening area, it's most commonly a curvature.

Symptoms include a lump or thickening along the shaft, a bent appearance, a painful erection, an inability to maintain an erection, or the inability to penetrate during sexual intercourse. While the cause of Peyronie's disease is still unknown, some experts believe it's caused by an excess of scar tissue due to an earlier injury (hitting or bending of the penis).

Though Peyronie's disease most often doesn't require treatment (it can go away on its own), vitamin E, injected steroids, or anti-inflammatory drugs can help treat pain and improve sexual function. In severe cases, surgery is considered in order to remove scar tissue or to shorten the unaffected side of the penis.

Pretty interesting, huh? To learn about the other two most-common penile problems, tune in tomorrow and Friday.

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Impotence (Erectile dysfunction)

FitSugar — Wed, 08 Oct 2008 17:35:36 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

FDA Warns about Dietary Supplements

In 2006 and 2007, the FDA issued numerous warnings about “natural” dietary supplements promoted for erectile dysfunction and sexual enhancement. These products -- marketed under names such as “True Man,” “Energy Max,” “Rhino Max”-- contain illegal substances that can interact with prescription drugs and dangerously lower blood pressure. The interaction risks are greatest for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates. The FDA has not approved any of these products and warns that consumers should not buy or use them.

Viagra and Similar Drugs Safe for Men with Diabetes

Phosphodiesterase inhibitors (PDE-5 inhibitors) are generally safe and often effective for men with diabetes, at least in the short term, according to a 2007 review published in the Cochrane Database. However, there is not enough evidence to determine if these drugs are safe for men with diabetes if used on a long-term basis. PDE-5 inhibitors include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). These drugs should be used with caution in men who have unstable heart disease, poorly controlled high blood pressure, or history of stroke. Discuss with your doctor whether a PDE-5 inhibitor drug is safe for you.

Testosterone Therapy Guidelines

In 2007, the Endocrine Society issued guidelines for testosterone treatment. The Endocrine Society advises that testosterone therapy works best for men who have been diagnosed with low testosterone levels and who demonstrate clear clinical symptoms such as erectile dysfunction. For patients with low libido or erectile dysfunction, but normal testosterone levels, it is unclear that testosterone therapy offers any benefits. Most experts recommend that patients with low testosterone levels and erectile dysfunction combine testosterone replacement therapy with a PDE-5 inhibitor drug.

Metabolic Syndrome Increases Risk for Erectile Dysfunction

Metabolic syndrome is a risk factor for erectile dysfunction, according to several recent studies. Metabolic syndrome is a cluster of conditions that include abdominal obesity, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance.

Introduction

Erectile dysfunction (impotence) is the inability to achieve or maintain an erection sufficiently rigid for sexual intercourse, ejaculation, or both. Sexual drive and the ability to have an orgasm are not necessarily affected. Because all men experience erection problems from time to time, doctors consider impotence to be present if attempts at intercourse fail at least 25% of the time.

Erectile dysfunction is new in neither medicine nor human experience, but it is not easily or openly discussed. Cultural expectations of male sexuality inhibit many men from seeking help for a disorder that can, in most cases, benefit from medical treatment. The term "impotence" comes from Latin and means loss of power; a more accurate term is "erectile dysfunction."

The Structure of the Penis. The penis is composed of the following structures:

Two parallel columns of spongy tissue called the corpus cavernosa, or erectile bodies.
A central spongy chamber called the corpus spongiosum, which contains the urethra, the tube that carries urine from the bladder through the penis.

These structures are made up of erectile tissue. Erectile tissue is rich in tiny pools of blood vessels called cavernous sinuses. Each of these vessels are surrounded by smooth muscles and supported by elastic fibrous tissue composed of a protein called collagen.

Erectile Function and Nitric Oxide. The penis is either flaccid or erect depending on the state of arousal. In the flaccid, or unerect, penis, the following normally occurs:

Small arteries leading to the cavernous sinuses contract, reducing the inflow of blood.
The smooth muscles regulating the many tiny blood vessels also stay contracted, limiting the amount of blood that can collect in the penis.

During arousal the following occurs:

The man's central nervous system stimulates the release of a number of chemicals, including nitric oxide, which is now considered the main contributor for eliciting and maintaining erection.
Nitric oxide stimulates production of cyclic GMP, a chemical that relaxes the smooth muscles in the penis. This allows blood to flow into the tiny pool-like cavernous sinuses, flooding the penis.
This increased blood flow nearly doubles the diameter of the spongy chambers.
The veins surrounding the chambers are squeezed almost completely shut by this pressure.
The veins are unable to drain blood out of the penis and so the penis becomes rigid and erect.
After ejaculation or arousal, cyclic GMP is broken down by an enzyme called phosphodiesterase-5 (PDE5), and other compounds are released that cause the penis to become flaccid (unerect) again.

A proper balance of certain chemicals, gases, and other substances is critical for erectile health:

Collagen. The protein collagen is the major component in structural tissue in the body, including in the penis. Excessive amounts, however, form scar tissue, which can impair erectile function.

Oxygen. Oxygen-rich blood is one of the most important components for erectile health. Oxygen affects two substances that are important in achieving erection:

Oxygen suppresses transforming growth factor beta 1 (TGF-B1). TGF-B1 is a component of the immune system called a cytokine and is produced by smooth muscle cells. It appears to stimulate collagen production in the corpus cavernosum, which can lead to erectile dysfunction.
Oxygen enhances the activity of prostaglandin E1. Prostaglandin E1 is produced during erection by the muscle cells in the penis. It activates an enzyme that initiates calcium release by the smooth muscle cells, which relaxes them and allows blood flow. Prostaglandin E1 also suppresses production of collagen.

Oxygen levels vary widely from reduced levels in the flaccid state to very high in the erect state. During sleep, oxygen levels are high and a man can normally have three to five erections per night, each one lasting from 20 - 40 minutes.

Testosterone and Other Hormones. Normal levels of hormones, especially testosterone, are essential for erectile function, though their exact role is not clear.

Erectile dysfunction most commonly occurs when the penis is deprived of oxygen-rich blood. When oxygen levels to the penis are low, an imbalance occurs in two important substances, TGF-B1 and prostaglandin E1:

TGF-B1 levels increase, which trigger production of collagen, a tough protein that forms all types of connective tissue, including scar tissue.
In addition, there is a reduction in prostaglandin E1, a chemical that suppresses collagen production and relaxes the smooth muscles to allow blood flow resulting in an erection.

When TGF-B1 levels increase and prostaglandin E1 levels decrease, smooth muscles waste away and collagen is overproduced, causing scarring, loss of elasticity, and reduced blood flow to the penis. A number of conditions can deprive the penis of oxygen-rich blood.

Blockage of Blood Vessels (Ischemia). The primary cause of oxygen deprivation is ischemia-- the blockage of blood vessels. The same conditions that cause blockage in the blood vessels leading to heart problems may also contribute to erectile dysfunction. For example, when cholesterol and other factors are imbalanced, a fatty substance called plaque forms on artery walls. As the plaque builds up, the arterial walls gradually narrow, reducing blood flow. This process, known as atherosclerosis, is the major contributor to the development of coronary heart disease. It may also play a role in the development of erectile dysfunction.

Risk Factors

More than 18 million American men over age 20 have erectile dysfunction, and about 600,000 men age 40 - 70 experience erectile dysfunction to some degree each year.

For most men, erectile dysfunction is primarily associated with older age. While ED affects less than 10% of men in their 20s, and 20 – 46% of men age 40 – 69, about 80% of men age 75 or older have ED. Nevertheless, impotence is not inevitable with age. In a survey of men over 60 years old, 61% reported being sexually active, and nearly half derived as much if not more emotional benefit from their sex lives as they did in their 40s.

Severe erectile dysfunction in elderly men may have more to do with disease than age itself. In particular, older men are more likely to have heart disease, diabetes, and high blood pressure than younger men. Such conditions and some of their treatments are major risk factors for erectile dysfunction. Smoking and obesity are also prime risk factors for ED.

Many physical and psychological situations can cause erectile dysfunction, and brief periods of impotence are normal. Every man experiences erectile dysfunction from time to time. Nevertheless, if the problem is persistent, men should seek professional help, particularly since erectile dysfunction is usually treatable and may also be a symptom of a more widespread problem.

Lifestyle or Psychological Causes

Over the past decades, the medical perspective on the causes of erectile dysfunction has shifted. Common wisdom used to attribute almost all cases of impotence to psychological factors. Now investigators estimate that up to 85% of impotence cases are caused by medical or physical problems. Only 15% are psychologically based.

It is often difficult to determine if the cause of erectile dysfunction is a physical or psychological one, or even some combination. The following may be helpful:

Physical impotence can be caused by internal medical causes (diabetes, high blood pressure) or by external causes (surgery, injury, medications). Erectile dysfunction due to medical conditions usually develops gradually but continuously over a period of time. If impotence persists over a 3-month period and is not due to a stressful event, drug use, alcohol, or known medical conditions, then the patient needs medical attention by a urologist specializing in impotence.
Psychological impotence tends to develop rapidly and be related to a recent situation or event. The patient may be able to have an erection in some circumstances but not in others. Being able to experience or maintain an erection upon waking up in the morning suggests that the problem is psychological rather than physical.

In virtually every case of erectile dysfunction there are emotional issues that can seriously affect the man's self-esteem and relationships. Negative emotions may even perpetuate erectile dysfunction that has been caused by a medical condition that has been successfully treated. Many men tend to fault themselves for their impotence even if it is clearly caused by physical problems over which they have little or no control.

Anxiety. Anxiety has both emotional and physical consequences that can affect erectile function. It is among the most frequently cited contributors to psychological impotence. Excessive concern about sexual performance is often referred to as performance or "honeymoon" anxiety and may provoke an intense fear of failure and self-doubt. It can sometimes set off a cycle of chronic impotence. In response to anxiety, the brain releases chemicals known as neurotransmitters that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis. Even simple stress may promote the release of brain chemicals that disrupt potency in a similar way.

Depression. Depression is strongly associated with erectile dysfunction. In one study, 82% of men who reported moderate-to-severe erectile dysfunction also had symptoms of depression. Depression can certainly reduce sexual desire, but it is often not clear which condition came first.

Troubles in relationships often have a direct impact on sexual functioning. Partners of men with erectile dysfunction may feel rejected and resentful, particularly if the affected man does not confide his own anxieties or depression. Both partners commonly experience guilt for what they each perceive as a personal failure. Tension and anger frequently arise between people who are unable to discuss sexual or emotional issues with each other. It can be very difficult for the man to perform sexually when both partners harbor negative feelings.

Losing a job or having lower income or education increases the risk for impotence.

Smoking contributes to the development of impotence, mainly because it increases the effects of other disorders of the blood vessels, including high blood pressure and atherosclerosis. A 2006 study found that men who smoked at least a pack a day were 39% more likely to experience ED than non-smokers. Research presented at the 2006 meeting of the American Urological Association indicated that quitting smoking helps reverse ED.

Alcohol has also been implicated in causing impotence. A small amount releases inhibitions, but having more than one drink can depress the central nervous system and impair sexual function.

Some evidence suggests that exposure to estrogen-like chemicals, such as those found in DDT and other pesticides, may contribute to erectile dysfunction. (Such chemicals have been associated with low sperm counts and infertility in men.)

Infrequent erections deprive the penis of oxygen-rich blood. Without daily erections, collagen production increases and eventually may form a tough tissue that interferes with blood flow. The spontaneous erections men have while sleeping or awake may be a natural protection against this process.

Physical Causes

A number of conditions share a common problem with erectile dysfunction -- the impaired ability of blood vessels to open and allow normal blood flow. Such conditions include diabetes, hypertension, coronary artery disease, kidney failure, peripheral artery disease, and stroke. Increasingly, researchers are studying the role of nitric oxide, which plays a major role in keeping blood vessels open, in all of these disorders.

The following diseases are highly associated with erectile dysfunction:

Heart Disease. Erectile problems may be a warning sign of heart disease. Several important studies in 2005 and 2006 firmly established this link. The studies indicated that men with ED are more likely to have coronary artery disease (CAD) and high blood pressure, and more severe forms of heart disease, than men without erectile problems. In fact, the studies suggested that ED is a stronger predictor of CAD than smoking, family history, cholesterol levels, or high blood pressure. Men who experience ED are at greater risk for angina, heart attack, or stroke. Many experts now recommend that men with erectile dysfunction undergo a complete cardiovascular evaluation.
High Blood Pressure (Hypertension). Erectile dysfunction is a very common problem in men with high blood pressure. More than 40 percent of men with erectile dysfunction have hypertension. The disease process is the major contributor to impotence, but many of the drugs used to treat hypertension also cause it. Newer anti-hypertensive drugs, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are less likely to cause erectile dysfunction. In fact, ARBs may be particularly effective in restoring erectile function in men with high blood pressure who suffer from impotence.
Diabetes. Diabetes is a major risk factor for erectile dysfunction. It may increase the risk for ED by as much as 169% and contribute to as many as 40% of impotence cases. Between a third and a half of all men with diabetes report some form of sexual difficulty. Blocked arteries and nerve damage are both common complications of diabetes. When the blood vessels or nerves of the penis are involved, erectile dysfunction can result. Diabetes is also associated with heart disease, another risk factor for ED.
Obesity. Obesity increases the risk for diabetes, heart disease, and erectile dysfunction. According to a 2006 study, obese men are 60% more likely to develop ED than normal weight men.
Metabolic Syndrome. Metabolic syndrome -- a cluster of conditions that includes obesity and abdominal fat, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance -- is also a risk factor for erectile dysfunction in men older than 50 years.

Parkinson's Disease. As a risk factor for impotence, Parkinson's disease (PD) is an under-appreciated problem. It is estimated that about a third of men with PD experience impotence. The physical cause of PD-related impotence is most likely an impaired nervous system. Depression and lowered self-esteem also contribute to erectile dysfunction in these patients.

Multiple Sclerosis. Multiple sclerosis (MS), which affects the central nervous system, also precipitates sexual dysfunction in as many as 78% of male patients. (Corticosteroids, which are common treatments for MS, may improve sexual function.)

Other Common Medical Conditions. Other medical conditions that have been associated with erectile dysfunction include allergies, thyroid problems, lung disease, and epilepsy.

Advanced prostate cancer can damage nerves needed for erectile function. Prostate surgery and surgical and radiation treatments for prostate cancer can also cause impotence. A number of treatments for sexual dysfunction are available that may help some men. [See In-Depth Report #33: Prostate cancer.]

Prostate Cancer Surgery (Radical Prostatectomy). The first nationally representative study to evaluate long-term outcomes after radical prostatectomy concluded that impotence occurs far more frequently than previously reported. Those who have so-called nerve-sparing surgeries have better results than those whose surgeries affect the nerves around the prostate. Some evidence also suggests that sexual function rates might improve if the nerve-sparing prostate surgeries also spare the ducts that carry semen.

Some studies suggest that impotence after prostate surgery may in part be due to injury to the smooth muscles in the blood vessels. Early treatments to maintain penile blood flow may help restore erectile function. Some men may benefit from PDE5 inhibitor drugs such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra). Other men may need alprostadil injections or suppositories. The vacuum pump is another option.

Radiation. Although it is generally believed that radiation poses a lower risk for impotence than does surgery, studies have reported similar rates after 3 years. Experts suggest radiation injures the blood vessels, leading to erectile dysfunction over time. Some studies report a lower risk for impotence from brachytherapy, a radiation technique that involves the implantation of radioactive "seeds" compared to external-beam radiation. Still, there have been very few studies that have lasted more than 2 years. One 5-year study reported a high long-term rate of impotence (53%) with brachytherapy, which is close to that of standard externally administered radiation. Early use of alprostadil injections and sildenafil (Viagra) may help these men as well as those who had surgery.

Drug Treatments. Prostate cancer medical treatments commonly employ androgen-suppressive treatments, which cause erectile dysfunction.

Surgery for Colon and Rectal Cancers. Surgical and radiation treatments for colorectal cancers can cause impotence in some patients. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short-term or long-term sexual dysfunction. Total mesorectal excision (TME) may pose fewer risks than standard surgery. Sildenafil (Viagra) may help many men who experience this after surgery.

Surgical Treatment of Inflammatory Bowel Disease. Rectal excision for inflammatory bowel disease (IBD) can cause impotence, but rates are low (2 - 4%). Sildenafil (Viagra) is very effective in restoring potency after IBD surgery.

Operations for Fistulas. Surgery to repair anal fistulas can affect the muscles that control the rectum (external anal sphincter muscles), sometimes causing impotence. (Repair of these muscles may restore erectile function.)

Surgery and drug treatments for benign prostatic hyperplasia (BPH) can also increase the risk for impotence, although to a much lesser degree than surgery for prostate cancer.

Between 4 - 10% of patients who have transurethral resection of the prostate (TURP) and open prostatectomy for BPH report impotence afterward. The risk is very low, however, in men who were functioning normally before surgery.
Finasteride (Proscar) has been associated with impotence in 6 - 19% of patients. Anti-androgen drugs used to treat BPH can also cause erectile dysfunction.

About a quarter of all cases of impotence can be attributed to medications. Many drugs pose a risk for erectile dysfunction. Some experts think that nearly every drug, prescription or nonprescription, can be a cause of temporary erectile dysfunction.

Drugs that commonly cause impotence may include:

Drugs used in chemotherapy.
Many drugs taken for high blood pressure, particularly diuretics and beta-blockers.
Most drugs used for psychological disorders, including anti-anxiety drugs, anti-psychotic drugs, and antidepressants, especially selective serotonin reuptake inhibitors (SSRIs). Newer antidepressants pose fewer problems.
Anti-androgens, including drugs known as gonadotropin-releasing hormone agonists. They are used in prostate cancer and also for treating BPH.

Drugs that sometimes cause impotence include:

Older anti-ulcer medications (cimetidine)
Anticholinergic drugs (including some antihistamines)
Antinausea drugs, particularly metoclopramide (Reglan)
Antifungal drugs (especially ketoconazole)
Nonsteroidal anti-inflammatory drugs (NSAIDs), when used on a daily basis

Injury to the Spine. Spinal cord injury and pelvic trauma, such as a pelvic fracture, can cause nerve damage that results in impotence. Other conditions that can injure the spine and effect impotence include spinal cord tumors, spina bifida, and a history of polio.

Orthopedic surgery. Erectile dysfunction can sometimes result from orthopedic surgery. A study of young men who underwent surgical repair (“intramedullary nailing”) for a broken thighbone reported that about 40% of these patients experienced erectile dysfunction after surgery. The researchers theorized that the surgery affected pelvic nerves that play a key role in erection. Patients who received a higher dose of muscle relaxant during surgery had better sexual function outcomes.

Bicycling. Studies have indicated that frequent bicycling may pose a risk for erectile dysfunction by reducing blood flow to the penis. The greatest risk is in cyclers who sit upright while cycling. In addition, a 2004 report in the Journal of Urology found that long distance cyclers may reduce their risk by riding a road bike instead of a mountain bike and by choosing saddles without a cutout.

Note: Vasectomy does not cause erectile dysfunction. When impotence occurs after this procedure, it is often in men whose female partners were unable to accept the operation.

Hypogonadism (Testicular Failure). Hypogonadism in men is a deficiency in male hormones, usually due to an abnormality in the testicles, which secrete these hormones. It affects 4 - 5 million men in the United States. In addition to impotence, hypogonadism causes reductions in energy, sex drive, lean body mass, and bone density. Hypogonadism can be caused by a number of different conditions. Among them are:

Disorders in the pituitary or hypothalamus glands
Malnutrition
Genetic factors
Myotonic dystrophy.
Orchitis (inflammation of the testicles)
Physical injury
Mumps
Radiation treatments
Exercise-induced hypogonadism. Only a few cases of exercise-induced hypogonadism have been identified in men. Some researchers believe, however, that certain athletes may be at risk, including those who began endurance training before full sexual maturity, have very low body weight, and have a history of stress fractures.

Low Testosterone Levels. Only about 5% of men who see a doctor about erectile dysfunction have low levels of testosterone, the primary male hormone. In general, lower testosterone levels appear to reduce sexual interest, not cause impotence.

Other Hormonal Abnormalities. Other hormonal abnormalities that can lead to erectile dysfunction include:

High levels of the female hormone estrogen (which may occur in men with liver disease).
Abnormalities of the pituitary gland that cause high levels of the hormone prolactin are particularly likely to cause impotence.
Other uncommon hormonal causes of impotence include an underactive or overactive thyroid or adrenal gland abnormalities.

A varicocele is an enlarged (varicose) vein in the cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men. When varicoceles occur in both testicles, they may contribute to hormone imbalances that cause erectile dysfunction.

Premature Ejaculation. Premature ejaculation is the most common male sexual dysfunction and occurs in as many as 40% of men. It is defined as the inability to delay ejaculation to the point where both partners are satisfied. This can vary widely depending on the preferences of the partners. Younger men tend to have this problem more than older men. Anxiety is a major factor at any age. In general, the longer the duration between ejaculations, the faster they are. Various techniques are available to help delay orgasm.

The standard medications used for this condition are selective serotonin reuptake inhibitors (SSRIs), which include Prozac and Paxil. Some studies suggest that sildenafil (Viagra) in combination with an SSRI may be helpful. A new serotonin-related drug, dapoxetine, showed promise in several clinical trials but was ultimately rejected by the FDA in 2005. There is still no drug specifically approved for treating premature ejaculation.

Peyronie's Disease. Peyronie's disease is an accumulation of scar tissue within the penis shaft, which causes it to curve. The curvature can make erection and intercourse difficult and painful. This condition may be associated with an injury to the penis, but no clear information exists on its origin. Some men may not even be aware that they have it, and there is some evidence that it may be more common than currently believed. In one study, 6.7% of men with an average age of 62 had signs of curvature, but only 2.2% were aware of any difficulties. The disease often goes into a type of spontaneous remission, and some individuals who had previously experienced erectile dysfunction are able to resume sexual activity. Scarring may still cause erection problems, however, even in these cases.

Treatment for Peyronie's Disease. If Peyronie's disease is treated early, ultrasound, heat application, and anti-inflammatory drugs may help reduce scar formation. Some experts believe that the extracorporeal shock wave therapy (ESWT) is the safest and most effective first-line therapy. ESWT uses sound waves to break up scar tissue. It has been used with some success.

Studies also suggest that the calcium channel blocker verapamil may be very beneficial. It can be administered using injection, as a gel patch, or through a process called electromotive drug administration (EMDA), also referred to as iontophoresis. EMDA delivers the drug through an electrical transport of charged molecules. Some studies are reporting good success with EMDA delivery of verapamil along with the steroid dexamethasone.

In severe cases of scarring, the only treatment is surgery to straighten the penis and reduce the curve. Penile implants may also be beneficial.

Priapism. Priapism is a sustained, painful, and unwanted erection that persists despite a lack of sexual stimulation. Generally, priapism results when the smooth muscle tissue remains relaxed so that a constant flow of blood into the vessels of the penis occurs with no leakage back out. The development of priapism has been associated with urinary stones, certain medications, neurologic disorders, and, more recently, with self-injection therapy used for impotence.

Treatment of Priapism. If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.

Prognosis

Temporary erectile dysfunction is very common and usually not a serious problem. Nevertheless, if the condition is persistent, psychological effects can be significant. Erectile dysfunction can have a devastating impact on a relationship and can cause extreme depression, which may become chronic if not treated. When a consistent pattern of sexual dysfunction extends over a prolonged period of time, a serious physical or emotional disorder may be present.

Persistent impotence may also be a symptom of a serious medical condition, such as heart disease, diabetes, hypertension, sleep disorders, or circulatory problems. For example, in a study of men who had suffered heart attacks, 75% of them had experienced erectile dysfunction on average 68 months before the heart attack.

Erectile dysfunction can also indicate the presence of injuries or the long-term effects of smoking, heavy drinking, or unhealthy diet.

Diagnosis

The doctor typically interviews the patient about many physical and psychological factors.

Medical and Personal History. The doctor should take a medical and personal history and may ask about the following:

Past and present medical problems
Medications or drugs being used
Any history of psychological problems, including stress, anxiety, or depression

Sexual History. In addition the doctor will ask about the patient's sexual history, which may include:

The nature of the onset of the dysfunction
The frequency, quality, and duration of any erections, and whether they occur at night or in the morning
The specific circumstances when erectile dysfunction occurred
Details of technique
The patient's motivation for and expectations of treatment
Whether problems exist in the current relationship

Interviewing the Sexual Partner. If appropriate, the doctor might also interview the sexual partner. In fact, including the partner in the counseling process is proving to be an important component in making the best treatment choices.

The doctor should perform a careful physical exam, including examination of the genital area and a digital rectal examination (the doctor inserts a gloved and lubricated finger into the patient's rectum) to check for prostate abnormalities.

A useful approach is to administer a treatment for erectile dysfunction and then observe the response. Doctors usually recommend a trial of sildenafil (Viagra) to test for an erection response 30 - 60 minutes after the drug is administered. This drug is replacing more invasive and expensive tests, such as an injection of papaverine or prostaglandin E1, medications that dilate blood vessels in the penis. They produce an erection in about 15 minutes.

After administering the treatment and waiting the appropriate amount of time, the doctor then observes the erectile response, curvature of the penis, and response after erection, sometimes using an ultrasound scanner to assess blood flow.

Blood Tests for Hormonal Abnormalities. Blood tests may be used to measure testosterone levels and, if necessary, prolactin levels to determine if there are hormone problems. The doctor may also screen for thyroid and adrenal gland dysfunction. In addition, various specific tests for erectile dysfunction can be performed.

Tests for Medical Conditions That May be Causing Erectile Dysfunction. Evidence of other medical conditions should be sought, particularly high blood pressure, diabetes, atherosclerosis, and nerve damage.

Tests that monitor nighttime erections may be used to determine if the causes of erectile dysfunction are more likely to be psychological than physical.

Snap-Gauge Test. The snap-gauge test monitors the man's ability to achieve an erection during sleep. It is a very simple test.

When the man goes to bed, he places bands around the shaft of his penis.
If one or more breaks during the course of the night, it provides evidence of an erection. In this case, a psychological basis for the erectile dysfunction is likely.

RigiScan Monitor. A more sophisticated and expensive device is the RigiScan monitor, which makes repetitive measurements of rigidity around the base and tip of the penis. This test is quite accurate but may fail to detect mild cases of erectile dysfunction.

The penile brachial index is a measurement that compares blood pressure in the penis with the blood pressure taken in the arm. Problems with the arterial flow to the penis can be detected using this method.

Imaging tests may be used in certain cases, but they are expensive and often limited to younger men. Anyone considering these tests should have them done in a specialized setting by professionals experienced in their use.

Dynamic Infusion Cavernosometry and Cavernosography. Dynamic infusion cavernosometry and cavernosography (DICC) is usually given only to young men in whom some blockage of the penis or physical injury of the pelvic area is suspected. After an erection is induced with drugs, the following four steps are taken:

The penile brachial index is taken.
The storage ability of the penis is gauged.
An ultrasound of the penile arteries is performed.
An x-ray of the erect penis is taken.

Unfortunately, this test and other similar imaging techniques used to determine blood flow in the penis are not very effective or accurate in diagnosing and determining treatment.

Duplex Doppler Ultrasound. An ultrasound technique called duplex Doppler ultrasound may be useful alone or with sildenafil (Viagra) in determining the severity of condition and also to determine impaired blood flow through the arteries.

Treatment

The cause of impotence dictates the mode of treatment. The first step is to define the cause, if possible, and then try the simplest and least-risky solution.

Before a certain treatment is prescribed, the following factors should be considered:

Any pre-existing illnesses and medications
The degree of comfort with the treatment method
Partner satisfaction and safety profiles need to be considered. Experts strongly recommend that the patient's partner be involved to help with any necessary sexual adjustment.

No matter what the treatment, embarking on a healthy lifestyle is the first and critical step for maintaining and restoring erectile function.

Medical and Surgical Treatments. Sildenafil (Viagra), the first effective oral drug for erectile dysfunction, has been on the market since 1998 and rapidly became the treatment of choice for most men with erectile dysfunction. In 2003, the FDA approved two other oral medications, vardenafil (Levitra) and tadalafil (Cialis), for the treatment of erectile dysfunction.

Men who cannot or choose not to take the drugs still have many other options, including:

Medications inserted or injected into the penis
Vacuum devices
Intracavernosal injection therapy
Invasive procedures, such as penile implants or surgery (limited to those for whom other treatments haven't worked and who have been carefully screened)

Ultimately, how successful the medical treatment is and how well it is accepted depends, in large part, on the man's expectations and how he and his partner both adapt to the procedure.

Psychotherapies. Some form of psychological, behavioral, or sexual therapy is often recommended for individuals suffering from severe impotence, regardless of cause.

Lifestyle Changes

Because many cases of erectile dysfunction are due to reduced blood flow from blocked arteries, it is important to maintain the same lifestyle habits as those who face an increased risk for heart disease.

Diet. Everyone should eat a diet rich in fresh fruits and vegetables, whole grains, and fiber and low in saturated fats and sodium. Because erectile dysfunction is often related to circulation problems, diets that benefit the heart are especially important.

Foods that some people claim to have qualities that enhance sexual drive include chilies, chocolate, scallops, oysters, olives, and anchovies. No hard evidence exists for these claims.

Exercise. A regular exercise program is extremely important. One study reported that older men who ran 40 miles a week boosted their testosterone levels by 25% compared to their inactive peers. Another study found that men who burned 200 calories or more a day in physical activity (which can be achieved by 2 miles of brisk walking) cut their risk of erectile dysfunction by half compared to men who did not exercise.

A study in the Journal of the American Medical Association found that adopting healthy lifestyle changes improved sexual function in obese men (BMI less than 30) with erectile dysfunction. After 2 years, a third of the study participants on the reduced calorie diet and an increased exercise regimen regained sexual function.

Limit Alcohol and Quit Smoking. Men who drink alcohol should do so in moderation. Quitting smoking is essential.

Staying sexually active can help prevent impotence. Frequent erections stimulate blood flow to the penis. It may be helpful to note that erections are firmest during deep sleep right before waking up. Autumn is the time of the year when male hormone levels are highest and sexual activity is most frequent.

The Kegel exercise is a simple exercise commonly used by people who have urinary incontinence and by pregnant women. It may also be helpful for men whose erectile dysfunction is caused by impaired blood circulation. The exercises consist of tightening and releasing the pelvic muscle that controls urination:

Since the muscle is internal and is sometimes difficult to isolate, practice first while urinating. (Once learned, however, Kegel exercises should not be regularly performed while urinating because doing them at that time may eventually weaken the muscles.)
Try to contract the muscle until the flow of urine is slowed or stopped. Attempt to hold each contraction for 10 seconds.
Then release the muscle.
Perform about 5 - 15 contractions three to five times daily.

It may be several months before the patient sees significant improvement.

If medications are causing impotence, the patient and doctor should discuss alternatives or reduced dosages.

Even if erectile dysfunction is caused by a physical problem, interpersonal, supportive, or behavioral therapy are often helpful for patients. Therapy may also ease the adjustment period after the initiation or completion of treatment. It is beneficial to have the partner involved in this process.

Medications

Three medicines taken by mouth are approved for the treatment of erectile dysfunction: Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). All three belong to a class of drugs called selective enzyme inhibitors. Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) block the enzyme phosphodiesterase-5 (PDE5). Blocking this enzyme helps maintain levels of cyclic guanosine monophosphate (GMP), a chemical produced in the penis during sexual arousal. Balanced levels of GMP cause the smooth muscles of the penis to relax and increase blood flow.

Good Candidates for PDE5 Inhibitors. PDE5 inhibitors are a good choice for men at any age and in any ethnic group who are in good health and who do not have conditions that preclude taking them (such as the use of nitrates or alpha-blockers; see Higher-risk candidates in this section.)

Effectiveness of PDE5 Inhibitors.

Tadalafil (Cialis). Tadalafil usually takes effect in 15 - 30 minutes. It is the only oral ED treatment shown to improve erectile dysfunction for up to 36 hours in most men. A randomized study of over 2,000 men found that nearly two-thirds reported successful intercourse attempts 24 - 36 hours after taking the drug.
Vardenafil (Levitra). Extensive clinical studies indicate that vardenafil improves erectile dysfunction in up to 85% of men with the condition. It also works well in patients with diabetes and in those who have had a radical prostatectomy.
Sildenafil (Viagra). Studies indicate that overall, sildenafil may help more than 70% of patients achieve sexual function.

Studies indicate that PDE5 inhibitors are safe and effective for many men whose erectile dysfunction is related to the following conditions:

Hormonal problems or psychologically induced impotence. These men achieve the highest success rates (80 - 100%).
Stable heart disease. However, PDE5 inhibitors should not be used by men who take nitrate drugs for chest pain or heart problems.
Mild-to-moderate heart failure. A study in the Archives of Internal Medicine found that men with moderate heart failure and ED can safely use sildenafil to improve their sexual function and overall quality of life, provided the men are not taking nitrates for their heart condition. Other research has also suggested that sildenafil is safe for this group of men.
Controlled high blood pressure.
Controlled diabetes (type 1 or 2). Diabetes has been associated with a lower than average response to sildenafil. Still, in a 2002 study over half of patients with type 2 diabetes achieved at least one successful sexual event.
Kidney conditions, including those that require chronic dialysis or kidney transplantation.
Parkinson's disease. Some evidence suggests that sildenafil may have properties that improve depression and help brain functions (attention, memory).
Depression. PDE5 inhibitors may help men who take antidepressant drugs that cause sexual dysfunction, notably selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac).

PDE5 inhibitors may also help restore erectile dysfunction in some men who have had the following conditions or treatments:

Treatments for prostate cancer. In men who have had radiation, advanced techniques, such as 3D conformal therapy, along with PDE5 inhibitors offer the best chances for success. In men who have had surgery, PDE5 inhibitors are most effective in younger men who were potent before surgery and who had bilateral nerve-sparing procedures. It is unlikely to be effective for men over age 55 who had unilateral or non-nerve-sparing procedures. Starting first with alprostadil injections right after treatment, followed by a PDE5 inhibitor, may be the best approach and considerably improve success rates.
Diabetes. PDE5 inhibitors appear to be safe and effective, at least in the short term, for most men with diabetes. There is not yet enough evidence to know whether these drugs are safe for long-term use.
Colon surgeries for cancer or inflammatory bowel disease.
Spina bifida, a congenital defect of the spinal cord.
Spinal cord injury. PDE5 inhibitors can be very effective in many of these men, especially those in which there is some erectile response and when the injuries are in the upper part of the spine.

Higher-Risk Candidates. PDE5 inhibitors are not suitable for everyone. Men who take nitrate drugs for angina, anticoagulants for heart conditions, or certain types of alpha-blockers for high blood pressure and benign prostatic hyperplasia (BPH), should not take PDE5 inhibitors. Men with the following conditions should not take PDE5 inhibitors without the recommendation of their doctors and even then should use them with caution:

Severe heart disease, such as unstable angina, a history of heart attack, or arrhythmias. Sildenafil increases nerve activity associated with cardiovascular function, especially during physical and mental stress. Men with heart disease may benefit from an exercise test to determine whether resuming sexual activity increases their risk of a heart attack.
Recent history of stroke
Hypotension (very low blood pressure)
Uncontrolled hypertension (high blood pressure)
Uncontrolled diabetes
Severe heart failure
Retinitis pigmentosa. (With this genetic disease, people do not produce phosphodiesterase-5 and do not respond to PDE5 inhibitors.)

Administration and Effect. PDE5 inhibitors work only when the man experiences some sexual arousal. They are generally effective within 30 - 120 minutes when taken on an empty stomach. Sildenafil should be taken on an empty stomach; vardenafil and tadalafil may be taken with or without food. The effects of these drugs may last for several hours. PDE5 inhibitors should not be used more than once a day.

Success rates increase with the number of attempts, so a man should not be discouraged if the drug does not work at first.

PDE5 inhibitors can also be used in combination with testosterone replacement therapy, but this combination may cause a number of side effects.

Side Effects and Other Limitations. Common side effects of PDE inhibitors include flushing, upset stomach, headache, nasal congestion, back pain, and dizziness.

Effects on the Heart. There have been reports of fatal heart attacks in a small percentage of men taking sildenafil (Viagra). Viagra can cause sudden and dangerous drops in blood pressure when the drug is taken with nitrate drugs, such as nitroglycerine, which are used for angina. No one taking nitrates, including the recreational drug amyl nitrate, should take sildenafil or any other PDE5 inhibitors.

Visual Effects. About 2.5% of men experience abnormal visual effects that include seeing a blue haze, temporary increased brightness, and even temporary vision loss in a few cases. Experts believe that visual disturbances are related to the inhibition of phosphodiesterase enzymes in the retina, but the effect appears to be temporary and insignificant, lasting a few minutes to several hours. Men at risk for eye problems who take PDE5 inhibitors regularly should have frequent eye examinations with an ophthalmologist. Men should also see an eye doctor if visual problems last more than a few hours.

In 2005, the FDA began investigating reports of partial vision loss in men who took sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). The vision loss was caused by non-arteric anterior ischemic optic neuropathy (NAION), a condition that occurs from poor blood flow to optic nerves. However, experts note that erectile dysfunction is itself linked to the same vascular problems that cause NAION. Patients who suffer from diabetes, high blood pressure, and heart disease are at higher risk for erectile dysfunction as well as other vascular problems such as NAION. Information concerning vision loss has been added to the labels of these drugs, but the risk of blindness appears small. Still, patients who use this medication and experience a sudden loss of vision should immediately stop taking the drug and contact their doctor.

Seizures. There have been a few reports of seizures in men taking sildenafil. These are rare occurrences and it is not clear if there is any causal association.

Risk of Priapism. PDE5 inhibitors pose a very low risk for priapism in most men. (Priapism is sustained, painful, and unwanted erection.) Exceptions are young men with normal erectile function.

Interactions with Other Drugs. In addition to serious interactions with nitrates, PDE5 inhibitors may also interact with certain antibiotics, such as erythromycin, and acid blockers, such as cimetidine (Tagamet). Patients should tell their doctor about any medications they are taking.

Decrease in Effectiveness. Over time, PDE5 inhibitors may lose effectiveness. A 2001 study found that after 2 years, 20% of patients had increased their dose of sildenafil to achieve the same effect, and 17% had discontinued the drug due to loss of efficacy. It is possible that these men were suffering from heart disease or other problems that made their impotence worse. An earlier study found that 96% of men who had been taking sildenafil for 2 - 3 years remained satisfied with the treatment. In addition, some research indicates that sildenafil treatment may be less effective in men with diabetes.

Other PDE5 Inhibitors. Avanafil and SLX-2101 are new PDE5 inhibitors that are showing promising results in clinical trials.

Melanocortin receptor agonists. Melanocortin receptor agonists work on the central nervous system instead of the vascular system. Bremelanotide (formerly PT-141) is the first of these drugs to be investigated in clinical trials. Researchers are testing the drug as a nasal spray given either alone or in combination with a PDE5 inhibitor.

Gene Therapy. Researchers are investigating gene transfer therapy as a possible cure for erectile dysfunction. Promising results from the first human trial were presented at the 2006 American Urological Association meeting. The gene-based therapy, called hMaxi-K, uses injections of a gene that helps the body manufacture proteins to improve smooth muscle relaxation. The treatment requires injections twice a year. It is still in the very early stages of research.

Injections or Topical Treatments

Penile injections have now largely been replaced by PDE5 inhibitors, such as sildenafil. Nevertheless, injection therapies use various drugs that have properties that help achieve erection, even in many men who do not succeed with PDE5 inhibitors. The standard drugs used in injections include:

Alprostadil
Phentolamine
Papaverine

Although any or all of these drugs are very effective, injections or other invasive methods of administration are awkward and uncomfortable.

Alprostadil is derived from a natural substance, prostaglandin E1, and acts by opening blood vessels. It is an effective treatment for some men. It can be administered by:

Injection into the erectile tissue of the penis (Caverject, Edex)
A device that administers the drug through the urethra (MUSE system)

Candidates. Regardless of how it is administered, alprostadil works in many men with a wide range of medical disorders related to erectile dysfunction, including men with:

Diabetes
Prostate cancer treatments (early use of alprostadil injections after prostate cancer treatment, particularly when followed by a PDE5 inhibitor, may be helpful)
Cholesterol problems treated with nitrates
Injury

Alprostadil is not an appropriate choice for men with:

Severe circulatory or nerve damage
Bleeding abnormalities or men who are taking medications that thin the blood, such as heparin or warfarin
Penile implants

Injected Alprostadil. Injected alprostadil (Caverject, Edex) uses a very small needle that the man injects into the erectile tissue of his penis. About 80% of men describe the pain of administering the injection as very mild. Edex is a newer and less expensive form of injected alprostadil. In one 12-month study of 894 patients, Edex injections achieved erections in 95% of attempts.

The drug should not be injected more than 3 times a week or more than once within a 24-hour period.

MUSE System. The MUSE system delivers alprostadil through the urethra. It works in the following way:

The device is a thin plastic tube with a button at the top.
The man inserts the tube into his urethral opening right after urination. (Urinating or urine leakage right after administration may reduce the amount of medication.)
He presses the button, which releases a pellet containing alprostadil.
The man rolls his penis between his hands for 10 - 30 seconds to evenly distribute the drug. To avoid discomfort, the man should keep the penis as straight as possible during administration.
The man should be upright, either sitting, standing or walking for about 10 minutes after administration. By that time, he should have achieved an erection that lasts between 30 - 60 minutes. (If a man lies on his back too soon after administration, blood flow to the penis may decrease and the erection may be lost.)
The erection may continue after orgasm.

The MUSE system should not be used more than twice a day and is not appropriate for men with abnormal penis anatomy.

Side Effects of Most Alprostadil Methods. Certain side effects are common to all methods of administration, although they may differ in severity depending on how the drug is given:

Pain and burning at the application site. In one study half of the men who injected alprostadil experienced some burning and pain at the injection site.
Scarring of the penis (Peyronie's disease), which is most likely to occur with injections.
Sudden, low blood pressure. Symptoms include dizziness, lightheadedness, and fainting. If these symptoms occur, the man should lie down immediately with his legs raised.
Priapism (prolonged erection). Possible with any method, but less chance with the MUSE system than with injections. If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.
Women partners may experience vaginal burning or itching. The drug may have toxic effects if it reaches the fetus in pregnant women, so men should not use alprostadil for intercourse with pregnant women without the use of a condom or other barrier contraceptive device.
Other side effects. Other side effects include minor bleeding or spotting, redness in the penis, and aching in the testicles, legs, and area around the anus.

Until the introduction of alprostadil, the two drugs used for injection therapy had been papaverine (Pavabid, Cerespan) and phentolamine (Regitine). Adverse reactions are usually minor but include pain, ulcers, and prolonged erections (priapism).

According to 2006 guidelines from the Endocrine Society, testosterone replacement therapy works best for men with erectile dysfunction who have been diagnosed with hypogonadism (low testosterone levels). For these men, experts recommend combination of testosterone and other ED treatments, such as PDE-5 inhibitors. Men who have ED and normal testosterone levels are not likely to benefit from testosterone therapy.

Forms of testosterone therapy include:

Muscle injections using testosterone enanthate (Andryl, Delatestryl) or cypionate (Andro-Cyp, Depo-Testosterone, Virion). This has been the standard administration.
Skin patch (Testoderm, Testoderm TTS, Androderm). Depending on the brand, patches may be applied to the skin of the scrotum every 24 hours or to the abdomen, back, thighs, or upper arm. In the latter case, two patches are required every 24 hours. Testoderm and Testoderm TTS may cause less skin irritation than Androderm.
Skin gel (Androgel, Testim). At this time, the gel is applied only to the same parts of the body as the patch. A gel applied to the penile skin is being investigated for men with hypogonadism and erectile dysfunction. Pregnant women must avoid contact with the gel because theoretically the testosterone could harm the fetus.

Oral forms of testosterone are not recommended because of the risk for liver damage when taken for long periods of time.

Testosterone therapy may increase the risk for the following adverse effects, particularly in men with normal testosterone levels:

Lowering of HDL ("good" cholesterol)
Rapid growth of prostate tumors in men with existing prostate cancers. (Taking testosterone does not appear to increase the risk for prostate cancer, but experts remain concerned.)
Lower sperm count
Sleep apnea
Polycythemia, an abnormal increase in red blood cells
Benign prostatic hyperplasia

Other Treatments

Vacuum devices, or external management systems, are effective, safe, and simple to use for all forms of impotence except when severe scarring has occurred from Peyronie's disease.

Using the Device. Patients must receive thorough instructions in the proper use of such devices. They typically work as follows:

The man places the penis inside a plastic cylinder.
A vacuum is created, which causes blood to flow into the penis, thereby creating an erection.
A band is tightly secured around the base of the penis, which retains the erection, and the cylinder is removed.
It takes about 3 - 5 minutes to produce an erection.

Lack of spontaneity is this method's major drawback. The erection involves only part of the penis shaft, and the process will certainly seem peculiar in the beginning. When these psychological obstacles are overcome, many couples find the result highly satisfactory.

Success Rates. Studies have found that success with the vacuum device is about equal to other methods. Between 56 - 67% of men using it reported the device to be effective. In one study of men who had used the vacuum device for many years, almost 79% reported improvement in their relationships with their sexual partners, and 83.5% said they had intercourse whenever they chose. Nevertheless, dropout rates are high. In one study, for example, the overall drop out rate was 65%. Even in a high-success group, over half stopped using it.

Side Effects. Side effects include blocked ejaculation and some discomfort during pumping and from use of the band. Minor bruising may occur, although infrequently. It is very important to use a medically approved pump. There have been reports of injury from vacuum devices that do not have a pressure-release valve or other safety elements.

Vacuum-less devices that trap blood within the penis are also available. They are called venous flow controllers or simple constricting devices. These devices are typically rubber or silicone rings or tubes that are placed at the base of the erect penis to trap the erection. They can be used by men who can achieve erections but lose them easily. These devices should not be used for longer than 30 minutes or lack of oxygen can damage the penis, and they should not be used by patients who have bleeding problems or are taking anticoagulant medicines ("blood thinners").

Penile implants are available for men who cannot take medication or who fail less invasive treatments. A 2006 study reported that penile implants helped restore sexual function to 89% of men who had the procedure, and 81% of men were satisfied with the results.

Three types of surgical implants are used for the treatment of erectile dysfunction:

A hydraulic implant consists of two cylinders placed within the erection chambers of the penis and a pump. The pump releases a saline solution into the chambers to cause an erection, and removes the solution to deflate the erection.
A penile prosthesis is composed of two semi-rigid but bendable rods that are placed inside the erection chambers of the penis. The penis can then be manipulated to an erect or non-erect position.
A third implant uses interlocking soft plastic blocks that can be inflated or deflated using a cable that passes through them.

There appear to be no long-term immune problems related to the silicon or other materials in the devices.

Limitations. Erectile tissue is permanently damaged when these devices are implanted and procedures are irreversible. Although uncommon, mechanical breakdown can occur, or the device can slip or bulge, especially if the patient coughs or vomits vigorously after the operation. In addition, a less than optimal quality of erection may result. (Using the MUSE system may restore or improve the function of a penile prosthesis in patients with a failed device.)

Complications. Infection is the major concern with these devices. Redness and fever often accompany a full-blown infection. Any intermittent pain that continues to occur after an implant may be an indicator of a low-grade infection. If the infection can be caught early enough, implant failure can be prevented. Most infections are treated with antibiotics for at least 10 - 12 weeks. If antibiotics fail, a surgical exchange, in which the infected implant is simultaneously replaced with a new one, should be considered. This is a complex procedure, but some surgeons have reported a 90% success rate.

For men whose impotence is caused by damage to the arteries or blood vessels, vascular surgery might be an option. Two types of operations are available: revascularization (bypass) surgery, and venous ligation. The American Urologic Association stresses that vascular surgery is still investigational.

Revascularization. The revascularization procedure usually involves taking an artery from a leg and then surgically connecting it to the arteries at the back of the penis, bypassing the blockages and restoring blood flow. In a related procedure called deep dorsal vein arterialization, a penile vein is used for the bypass. Young men with local sites of arterial blockage or those with pelvic injuries generally achieve the best results. In studies of selected patients there was improvement in erectile dysfunction in 50 - 75% of men after 5 years.

Venous Ligation. Venous ligation is performed when the penis is unable to store a sufficient amount of blood to maintain an erection. This operation ties off or removes veins that are causing an excessive amount of blood to drain from the erection chambers. The success rate is estimated at between 40 - 50% initially, but drops to 15% over the long term. It is important to find a surgeon experienced in this surgery. In a variation of this technique called venous ablation, ethanol is injected into the deep dorsal vein, the main vein that drains blood from the penis. The ethanol causes scarring that closes off smaller veins and prevents blood leakage, thereby bolstering erectile function.

Natural Remedies

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

The following are special concerns for people taking alternative remedies for erectile dysfunction:

Yohimbe. Yohimbe, which is similar to yohimbine, is derived from the bark of a West African tree. Side effects include nausea, insomnia, nervousness, and dizziness. Large doses of yohimbe can increase blood pressure and heart rate and may cause kidney failure.

Gamma-Butyrolactone (GBL). GBL is found in products marketed for improving sexual function (Verve, Jolt). This substance can convert to a chemical that can cause toxic and life-threatening effects, including seizures and even coma.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses and interaction with vitamin E, anti-clotting medications, and aspirin and other NSAIDs. Large doses can cause convulsions. Commercial gingko preparations have also been reported to contain colchicine, a substance that can be harmful in people with kidney or liver problems.

L-arginine (also called arginine). Arginine may cause gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in some cases may be severe. It may worsen asthma.

DHEA. DHEA is a supplement related to certain male and female hormones. Studies show inconclusive results in its treatment for erectile dysfunction. DHEA may interact dangerously with other medications.

Aphrodisiacs. Aphrodisiacs are substances that are supposed to increase sexual drive, performance, or desire. Examples include:

Viramax is a well-marketed product that contains yohimbine and three herbal aphrodisiacs: catuaba, muira puama, and maca. It has not been proven to be either effective or safe, and interactions with medications are unknown.
Spanish fly, or cantharides, which is made from dried beetles, is the most widely-touted aphrodisiac but can be particularly harmful. It irritates the urinary and genital tract and can cause infection, scarring, and burning of the mouth and throat. In some cases, it can be life threatening. No one should try any aphrodisiac without consulting a doctor.

Other Alternative Products Marketed for Erectile Dysfunction. Vinarol is an over-the-counter supplement that was recalled by the FDA in 2003 after reports surfaced that it contained the same ingredients found in Viagra. Herbal supplements sold as Viagro and Vaegra have no association with Viagra. There are numerous other products marketed as “all-natural” dietary supplements and promoted as treatments for erectile dysfunction and sexual enhancement. The FDA has not approved any of these products and has issued many warnings concerning them. In 2006 and 2007, the FDA warned that “True Man,” “Energy Max,” “Rhino Max,” “VMax,” Libidus,” and similar dietary supplements contain illegal chemicals that can interact with prescription drugs and cause dangerously low blood pressure. These products are particularly dangerous for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates.

Resources

www.niddk.nih.gov -- National Kidney and Urologic Diseases Information
www.auanet.org -- American Urologic Association
www.urologyhealth.org -- Urology Health

References

Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006 Jun;91(6):1995-2010. Epub 2006 May 23.

Heidler S, Temml C, Broessner C, Mock K, Rauchenwald M, Madersbacher S, et al. Is the metabolic syndrome an independent risk factor for erectile dysfunction? J Urol. 2007 Feb;177(2):651-4.

Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007 Feb;120(2):151-7.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

Review Date:
6/27/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Sickle cell disease

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Risk Factors
Symptoms
Diagnosis
Outlook
Complications
Treatment
Prevention and Lifestyle Ch...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Screening for Sickle Cell Disease

The United States Preventive Services Task Force’s 2007 guidelines recommend that all newborn infants be screened for sickle cell disease. (In the United States, most states require hospitals to perform this test.) Early detection of sickle cell disease ensures that babies will be given treatment to prevent infections. Sickle cell disease is an inherited condition. About 1 in 375 African-American babies are born with sickle cell disease, but children of other ethnicities are also at risk.

Infections and Sickle Cell Disease

Children with sickle cell disease are highly susceptible to many life-threatening infections, including those caused by the pneumococcus bacterium. Pneumococcal vaccinations are an important protection against this bacterium. Research published in 2007 in Clinical Infectious Diseases indicates that the introduction of the pneumococcal conjugate vaccine has helped reduce by 90% the rate of pneumococcal infections in children with sickle cell disease. Four doses of this vaccine are given from age 2 - 15 months. A second type of pneumococcal vaccine, pneumococcal saccharide, is given when the child reaches 2 years of age.
Daily antibiotics given from age 2 months through 5 years can help prevent many other types of bacterial infections, such as meningitis and blood infections.

Introduction

Blood has two major components:

Plasma is a clear yellow liquid that contains proteins, nutrients, hormones, electrolytes, and other substances. It constitutes about 55% of blood.
White and red blood cells and platelets make up the balance of blood. The white cells are the infection fighters for the body, and platelets are necessary for blood clotting. The important factors in anemia, however, are red blood cells.

Red blood cells (RBCs), also known as erythrocytes, carry oxygen throughout the body to nourish tissues and sustain life. Red blood cells are the most abundant cells in our bodies. Men have about 5.2 million red blood cells per cubic millimeter of blood, and women have about 4.7 million red blood cells per cubic millimeter of blood. To understand red blood cells and their role in anemia, it is useful to know certain facts about them.

Hemoglobin and Iron. Each red blood cell contains about 280 million hemoglobin molecules. Hemoglobin is a complex molecule and the most important component of red blood cells. It is composed of protein (globulin) and a molecule (heme), which binds to iron.

In the lungs, the heme component binds to oxygen in exchange for carbon dioxide. The red blood cells carry the oxygen to the body's tissues, where the hemoglobin releases the oxygen in exchange for carbon dioxide, and the cycle repeats. The oxygen is used in the mitochondria, the power source within all cells.

Structure and Shape. Red blood cells are extremely small and look something like tiny, flexible inner tubes. This unique shape offers many advantages:

It provides a large surface area to absorb oxygen and carbon dioxide.
Its flexibility allows it to squeeze through capillaries, the tiny blood vessels that join the arteries and veins.
Abnormally shaped or sized erythrocytes are typically destroyed and eliminated.

Blood Cell Production (Erythropoiesis). The actual process of making red blood cells is called erythropoiesis. (In Greek, erythro means "red" and poiesis means "the making of things.") The process of manufacturing, recycling, and regulating the number of red blood cells is complex and involves many parts of the body:

The body carefully regulates its production of red blood cells so that enough are manufactured to carry oxygen but not so many that the blood becomes thick or sticky (viscous).
Most of the work of erythropoiesis occurs in the bone marrow.
If the body needs more oxygen (at high altitudes, for instance), the kidney triggers the release of erythropoietin (EPO), a hormone that increases production of red blood cells in the bone marrow.
The lifespan of a red blood cell is 90 - 120 days. The liver and spleen remove old red blood cells from the blood.
When old red blood cells are broken down for removal, iron is returned to the bone marrow to make new cells.

Sickle cell disease occurs from genetic changes which causes a portion of the hemoglobin molecules to be abnormal:

Hemoglobin A (HbA). HbA is the hemoglobin molecule found in normal red blood cells during childhood and adulthood. People without sickle cell anemia have primarily this type of hemoglobin in their blood cells.
Hemoglobin S (HbS). HbS (S is for sickle) is the abnormal variant of hemoglobin A, which occurs in sickle-red blood cells and is the primary characteristic of the disease. The difference between hemoglobin A (HbA) and hemoglobin S (HbS) lies in only one protein out of about 300 that are common to both. This protein lies along an amino-acid chain called beta-globin, where even a tiny abnormality has disastrous results.

Hemoglobin is the most important component of red blood cells. It is composed of a protein called heme, which binds oxygen. In the lungs, oxygen is exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in red blood cell balance. Both low and high values can indicate disease states.

Hemoglobin F (HbF) is a form of hemoglobin that is produced during fetal development in the womb. (The F in HbF stands for fetal.) It is usually present for only a short time after birth. Normally, most HbF is later replaced by HbA, although some HbF may persist throughout life. Importantly, HbF is able to block the sickling action of red blood cells. Infants who have inherited sickle cell disease do not develop symptoms of the illness while they still have HbF present in their blood. People with the sickle cell gene who continue to carry some fetal hemoglobin are better protected, therefore, from severe forms of the disease. This knowledge is being used as the basis for therapies used in treating sickle cell disease.

The symptoms and problems of sickle cell disease are a result of the hemoglobin S (HbS) molecule:

When the sickle hemoglobin molecule loses its oxygen, it forms rigid rods called polymers that change the red blood cells into a sickle or crescent shape.
These abnormally sickle-shaped cells are both rigid and sticky. They stick to the walls and cannot squeeze through the capillaries. Blood flow through tiny blood vessels becomes slowed or stopped throughout the body. This deprives tissues and organs of oxygen.
In the immediate setting, oxygen deprivation (hypoxia) can cause severe pain (the sickle cell crisis). Over time, it leads to gradual destruction in organs and tissues throughout the body.

Click the icon to see an image of sickle cells.

In a vicious cycle, oxygen deprivation in cells leads to more polymerization and increased production of sickle cells. The higher the concentration of sickle hemoglobin and the more acidic the environment, the faster the sickle cell process.
Cell dehydration (not enough water molecules) is another major destructive factor in the sickling process of red blood cells. Dehydration increases the density of hemoglobin S within the cell, thereby speeding up the sickling process.
Sickle cells also have a shorter life span (10 - 20 days) than that of normal red blood cells (90 - 120 days). Every day the body produces new red blood cells to replace old ones, but sickle cells become destroyed so fast that the body cannot keep up. The red blood cell count drops, which results in anemia. This gives sickle cell disease its more common name, sickle cell anemia.

The severity of sickle cell disease generally depends on a number of factors:

The extent of oxygen loss. Prolonged oxygen deprivation contributes to the severe pain experienced as a sickle cell crisis. It also produces both short- and long-term organ damage. The lungs are specifically critical targets of the disease process. Because they supply oxygen, they can restore the sickle molecules to a normal form. Unfortunately, once the process occurs, the lungs become major sites for sickle cell damage, particularly for dangerous acute episodes of chest pain.
The acidity of the environment. The lower the better. The organs most seriously affected are those with an acidic environment (such as the spleen and bone marrow).
The concentration of hemoglobin S within the cell. The lower the better.
The amount of a protective hemoglobin F (for fetal). The more the better.

Risk Factors

Sickle cell disease is inherited. People at risk for inheriting the gene for sickle cell descend from people who are or were originally from Africa and parts of India and the Mediterranean. The sickle cell gene also occurs in people from South and Central America, the Caribbean, and the Middle East. The high incidence of the sickle cell gene in these regions of the world is due to the sickle cell's ability to make red blood cells resistant to the malaria parasite:

People who inherit just a single gene are referred to as having the sickle trait. These people are protected against malaria and do not develop sickle cell disease. About 40% of people in certain parts of Africa and about 9% of African-Americans have the trait.
Those who inherit both copies of the HbS gene develop sickle cell disease. They are not protected from malaria, however. In fact, malaria is more serious in these individuals. An estimated 1 in 500 African-Americans and 1 in 1,000 - 1,400 Hispanic Americans are born with sickle cell disease.

The sickle cell gene for hemoglobin S (HbS) is the most common inherited blood condition in America. About 72,000 Americans -- mostly African-Americans -- have sickle cell disease. The risk for inheriting sickle cell disease from parents with the sickle cell gene is as follows:

One parent has only one copy of the sickle cell gene and the other parent has two normal hemoglobin genes, and the child inherits a healthy gene from each parent. The child will not inherit either the disease or the trait.
The child inherits one copy of the sickle cell gene. The child has the trait (HbS) only. The other, healthy hemoglobin gene overrides HbS and blocks the development of sickle cell disease. Such people lead normal lives.
The child inherits the hemoglobin S gene from both parents (HbSS). The child develops the full-blown disease. (If each parent has one copy of the gene, the child has a 25% chance of acquiring the disease.)
The child inherits one hemoglobin S gene and one abnormal hemoglobin gene from other causes (such as one form called HbSC). Such children may develop a form of sickle cell disease. It is often a milder variant, but children can experience severe symptoms. They are also at risk for some of the complications of sickle cell disease, although their risks for serious problems are lower than in children with the full-blown disease.

Symptoms

General Symptoms in Infants. In infants, symptoms do not usually appear until late in the baby's first year. Most commonly, they include:

Fever
Swelling of the hands and feet
Pain in the chest, abdomen, limbs, and joints
Nosebleeds and frequent upper respiratory infections

General Symptoms in Childhood. Pain is the most common complaint. It can be acute and severe or chronic, usually from orthopedic problems in the legs and low back. Other symptoms include:

Anemia
Fatigue
Irritability
Jaundice (yellowish discoloration of the skin and eyes)
Bedwetting

Additional Symptoms in Adolescence or Adulthood. Symptoms of childhood continue in adolescence and adulthood. In addition, patients may experience:

Delayed puberty (in young teenagers)
Severe joint pain
Progressive anemia
Leg sores
Gum disease

The hallmark of sickle cell anemia is a group of devastating symptoms known collectively as a sickle cell crisis (also sometimes known as a vaso-occlusive crisis). Sickle cell crises are episodes of pain that occur with varying frequency and severity in different patients and are usually followed by periods of remission. Severe sickle cell pain has been described as being equivalent to cancer pain and more severe than postsurgical pain. It most commonly occurs in the lower back, leg, abdomen, and chest, usually in two or more locations. Episodes usually recur in the same areas.

The risk for a sickle cell crisis is increased by any activity that boosts the body's requirement for oxygen, such as illness, physical stress, or being at high altitudes. In more than half the cases, however, the trigger is unknown. Acute chest syndrome is a particularly serious complication of sickle cell crisis. It occurs in the lungs and can be extremely serious and even life threatening.

Diagnosis

Prenatal diagnosis of sickle cell disease is now possible for women who may be at risk for having a child with the disease. A positive result for sickle cell disease, however, poses extremely difficult questions even for parents who are not opposed to abortion.

A genetic test known as preimplantation genetic diagnosis (PGD) may prove to determine the presence or absence of the sickle cell mutation in embryos (fertilized eggs) before they are implanted in the mother during assisted fertilization techniques. This genetic tool may eventually help avoid the often emotionally devastating effects of abortion.

In the United States, most hospitals screen newborn babies for sickle cell disease. To perform the test, a blood sample is taken from the baby's heel using a simple needle prick. Early detection of sickle cell disease can help reduce the risk for life-threatening infections and increase the odds for survival. Babies who are diagnosed with sickle cell disease are given daily antibiotics to help prevent infections.

Unfortunately, no tests can definitely determine which children are at highest risk for a stroke and, therefore, would be candidates for ongoing blood transfusions. The following are diagnostic tools currently used or under investigation:

Transcranial Doppler (TCD) ultrasonography measures the speed of blood flow in the brain and is the most sensitive method to date for identifying children at risk for stroke. However, high-risk children are still vulnerable to stroke even if the TCD screening diagnosed normal blood flow velocities.
The use of follow-up magnetic resonance imaging (MRI) to detect small blockages in blood vessels may help confirm high risk in patients identified by TCD ultrasound.
Some patients may need to undergo angiography, an invasive diagnostic technique useful for detecting aneurysms.
Researchers are also beginning to uncover possible genetic markers that may eventually be used to help identify sickle cell patients at higher risk for stroke.

Outlook

New and aggressive treatments for sickle cell disease are prolonging life and improving its quality. As recently as 1973, the average lifespan for people with sickle cell disease was only 14 years. Currently, life expectancy for these patients can reach 50 years and over. Early studies showed that women had a greater risk for death from sickle cell disease than men, but experts now believe this was due to high mortality during pregnancies before the mid-1970s. Women with sickle cell disease now actually live longer than their male counterparts.

The damage and durability of sickle cell disease occurs because the logjam that sickle cells cause in the capillaries slows the flow of blood and reduces the supply of oxygen to various tissues. Not only does pain occur when body tissues are damaged by lack of oxygen, but serious and even life-threatening complications can result from severe or prolonged oxygen deprivation. Sickle cell disease is referred to in some African languages as "a state of suffering," but the disease has a wide spectrum of effects, which vary from patient to patient. In some people, the disease may trigger frequent and very painful sickle cell crises that require hospitalization. In others, it may cause less frequent and milder attacks.

Children with sickle cell disease are very susceptible to infections, usually because their damaged spleens are unable to protect the body from bacteria. A recent study suggested that signs of impaired lung function occur even in very early years. As medical progress has increased the lifespan of children with sickle cell disease, older patients are now facing medical problems related to the long-term adverse effects of the disease process. The most serious dangers are acute chest syndrome, long-term damage to major organs, stroke, and complications during pregnancy such as high blood pressure in the mother and low birth weight.

Complications

There is still no cure for sickle cell disease other than experimental transplantation procedures, but treatments for complications of sickle cell have prolonged the lives of many patients who are now living into adulthood.

The hallmark of sickle cell disease is the sickle cell crisis (also sometimes known as a vaso-occlusive crisis), which is an episode of pain. It is the most common reason for hospitalization in sickle cell disease. The pattern may occur as follows:

In general, the risk for a sickle cell crisis is increased by any activity that boosts the body's requirement for oxygen, such as illness, physical stress, or being at high altitudes. In more than half of episodes, however, the trigger is unknown.
Episodes typically begin at night and last 3 - 14 days, accelerating to a peak over several days and then declining.
The pain is typically described as sharp, intense, and throbbing. Severe sickle cell pain has been described as being equivalent to cancer pain and more severe than postsurgical pain. Shortness of breath is common.
Pain most commonly occurs in the lower back, leg, hip, abdomen, or chest, usually in two or more locations. Episodes usually recur in the same areas. Pain in the bones (usually occurring symmetrically on both sides) is common because blood obstruction can directly damage bone and because bone marrow is where red blood cells are manufactured.
The liver or spleen may become enlarged, causing pain in the upper right or upper left sides of the abdomen. Liver involvement may also cause nausea, low-grade fever, and increasing jaundice.
Males of any age may experience prolonged, often painful erections, a condition called priapism.

Episodes cannot be predicted, and they vary widely among different individuals. In one study, nearly 40% of patients reported no painful episodes over a 5-year period. About 5% of patients experienced severe and frequent episodes (more than three a year). They sometimes become less frequent with increasing age. Generally, people can resume a relatively normal life between crises. Most patients are pain-free between episodes although pain can be chronic in some cases.

Acute chest syndrome (ACS) occurs when the lungs are deprived of oxygen during a crisis. It can be very painful, dangerous, and even life threatening. It is a leading cause of illness among sickle cell patients and is the most common condition at the time of death. At least one whole segment of a lung is involved, and the following symptoms may be present:

Fever of 101.3°F degrees (38.5°C) or above
Rapid or labored breathing
Wheezing or cough
Acute chest pain

Pain often lasts for several days. In about half of patients, severe pain develops about 2 - 3 days before there are any signs of lung or chest abnormalities. Acute chest syndrome is often accompanied by infections in the lungs, which can be caused by viruses, bacteria, or fungi. Pneumonia is often present. A dull, aching pain usually follows, which most often ends after several weeks, although it may persist between crises.

Air is breathed in (inhaled) through the nasal passageways, and travels through the trachea and bronchi to the lungs.

Causes of Acute Chest Syndrome. Primary causes of acute chest syndrome include:

Infection. Infection from viruses or small atypical organisms (Chlamydia and Mycoplasma) is the most common cause of the oxygen deprivation that leads to acute chest syndrome.
Blockage of blood vessels. Blockage in the blood vessels (called infarction) that cuts off oxygen in the lungs is another important cause of acute chest syndrome. Blockage may be produced by blood clots or fat embolisms. (Fat embolisms are particles formed from fatty tissue in the bone marrow that enter and travel through the blood vessels.)
Asthma. Asthma can increase the frequency and pain of acute chest syndrome episodes in children, according to an important 2006 study. The researchers recommended that all children with sickle-cell disease who have frequent acute chest syndrome attacks should be evaluated for asthma.

In about 45% cases, the cause cannot be established. Some cases of acute chest syndrome may result from treatments of the crisis, including from administration of opioids (which reduce oxygen) or excessive use of intravenous fluids. Other lung diseases may also trigger ACS.

Severity of Acute Chest Syndrome. The mortality rates for ACS are around 2% in children and 4% in adults. The syndrome and its long-term complications are the major causes of death in older patients. The condition is four times more deadly in adults than in children. The longer a patient survives, the greater is the damage done by repetitive sickle cell crises in the chest and lungs.

The following destructive effects can occur:

Damage in the chest area from recurrent episodes increases susceptibility to invading infections, even those that are ordinarily not harmful. Infections frequently clear up if they are limited to small areas of the lung, but if they spread, they can progress very quickly and become life threatening.
Lung damage over time can lead to obstruction in the airways in lungs, causing asthma-like conditions.

Infections are common and an important cause of severe complications in sickle cell patients. Before early screening for sickle cell disease and the use of preventive antibiotics in children, 35% of infants with sickle cell died from infections. Fortunately, with screening tests for sickle cell now required for newborns in most states, and with the use of preventive antibiotics in babies who are born with the disease, this terrible mortality rate has dropped significantly.

Infections in Infants and Toddlers with Sickle Cell Disease. The most common organisms causing infection in children with sickle cell disease include:

Streptococcus pneumoniae (can cause blood infections or meningitis)
Haemophilus influenza (a cause of meningitis)

Such infections pose a grave threat to infants and very young children with sickle cell disease. They can progress to fatal pneumonia with devastating speed in infants, and death can occur only a few hours after onset of fever. The risk for pneumococcal meningitis, a dangerous infection of the central nervous system, is also significant.

Infections in Children and Adults. Infections are also common in older children and adults with sickle cell disease, particularly respiratory infections such as pneumonia, kidney infections, and osteomyelitis, a serious infection in the bone. (The organisms causing them, however, tend to differ from those in young children.) Infection-causing organisms include:

Chlamydia and Mycoplasma pneumoniae. These are the important infections in acute chest syndrome (see above).
Gram-negative bacteria. This group of bacteria mostly infects hospitalized patients and can cause serious pneumonias and other infections.

About 30% of patients with sickle cell disease have pulmonary hypertension. Pulmonary hypertension is a serious and potentially deadly condition that develops when pressure in the arteries of the lungs increases. It is an often unrecognized complication and cause of death in sickle cell disease. Many doctors recommend that all adults with sickle cell disease undergo echocardiographic testing to identify if they are at risk for pulmonary hypertension and require treatment.

Researchers are developing new types of tests that may help with early identification of pulmonary hypertension. For example, some studies indicate that a simple blood test for the hormone brain natriuretic peptide (BNP) could help identify patients with sickle cell pulmonary hypertension. Higher levels of BNP are associated with increased pressure in the pulmonary (lung) arteries. A blood test measuring levels of the enzyme lactate dehydrogenase (LDH) may also help identify patients at risk for pulmonary hypertension, as well as leg ulcerations and priapism (persistent and painful erection of the penis). Echocardiography or other tests would still need to be performed to confirm results from these blood tests.

The primary symptom of pulmonary hypertension is shortness of breath, which is often severe. Pulmonary hypertension can be very serious and life threatening in the short- and long-term. If pulmonary hypertension develops suddenly it can cause respiratory failure, which is life threatening. Over time, pulmonary hypertension may cause a condition called cor pulmonale, in which the right side of the heart increases in size. In some cases, this enlargement can lead to heart failure.

Click the icon to see an image of cor pulmonale.

After acute chest syndrome, stroke is the most common killer of patients with sickle cell disease who are older than 3 years old. Between 8 - 10% of patients suffer strokes, typically at about age 7. Patients may also suffer small strokes that may not be immediately noticeable. However, patients who have many of these small strokes may over time start behaving differently or have worsening mental functioning.

Strokes are usually caused by blockages of vessels carrying oxygen to the brain. Patients with sickle cell disease are also at high risk for stokes caused by aneurysm, a weakened blood vessel wall that can rupture and hemorrhage. Multiple aneurysms are common in sickle cell patients, but they are often located where they cannot be treated surgically.

Click the icon to see an image of stroke.

Anemia is a significant characteristic in sickle cell disease (which is why the disease is commonly referred to as sickle cell anemia).

Severe worsening of anemia. Children, adolescents, and possibly young adults may experience what is called splenic sequestration. This happens when a large amount of the sickled red blood cells collect in the patient's spleen. Symptoms may include pain in the right abdomen below the ribs and a large mass (the swollen spleen) may be felt.

Chronic Anemia. Because of the short lifespan of the sickle red blood cells, the body is often unable to replace red blood cells as quickly as they are destroyed. This causes a particular form of anemia called hemolytic anemia. Most patients with sickle cell disease have a hemoglobin levels of 8 g/dL, much lower than people without sickle cell anemia. Chronic anemia reduces oxygen and increases the demand on the heart to pump more oxygen-bearing blood through the body. Eventually, this can cause the heart to become dangerously enlarged, with an increased risk for heart attack and heart failure.

On occasion, patients may experience what is called an aplastic crisis. This happens when the cells in the bone marrow that are normally trying to make new red blood cells suddenly stop working. This sudden stopping is often triggered by a virus called human parvovirus B19.

The kidneys are particularly susceptible to damage from the sickling process. Persistent injury can cause a number of kidney disorders, including infection. Problems with urination are very common, particularly uncontrolled urination during sleep. Patients may have blood in the urine, although this is usually mild and painless and resolves without damaging consequences. Kidney failure is a major danger in older patients and accounts for 10 - 15% of deaths in sickle cell patients. Renal medullary carcinoma is an aggressive, rapidly destructive tumor in the kidney that is rare but can occur as a result of sickle cell disease.

Click the icon to see an image of kidney anatomy.

A reported 38 - 42% of males, including children, with sickle cell disease suffer from priapism. Priapism causes prolonged and painful erections that can last from several hours to days. Experts think that priapism in sickle cell disease may be caused by the destruction of red blood cells and subsequent reduction of nitric oxide. If priapism is not treated, partial or complete impotence can occur in 80% of cases.

Click the icon to see an image of the male reproductive anatomy.

Enlargement of the liver occurs in over half of sickle cell patients, and acute liver damage occurs in up to 10% of hospitalized patients. Because sickle cell patients often need transfusions, they have been at higher risk for viral hepatitis, an infection of the liver. This risk, however, has decreased since screening procedures for donated blood have been implemented.

About 30% of children with sickle cell disease have gallstones, and by age 30, 70% of patients have them. In most cases, gallstones do not cause symptoms for years. When symptoms develop, patients may feel overly full after meals, have pain in the upper right quadrant of the abdomen, or have nausea and vomiting. Acute attacks can be confused with a sickle cell crisis in the liver. Ultrasound is usually used to confirm a diagnosis of gallstones. If the patient does not have symptoms, no treatment is usually necessary. If there is recurrent or severe pain from gallstones, the gallbladder may need to be removed. Minimally invasive procedures (using laparoscopy) reduce possible complications. [For more information, see In-Depth Report #10: Gallstones.]

Click the icon to see an image of cholithiasis.

The spleen of most adults with sickle cell anemia is nonfunctional due to recurrent episodes of oxygen deprivation that eventually destroy it. Injury to spleen causes problems in immune function and increases the risk for serious infection. A very serious anemic condition called acute splenic sequestration crisis (sudden spleen enlargement) can occur if the damaged spleen suddenly becomes enlarged from trapped blood.

Click the icon to see an image of an enlarged spleen.

In some children with sickle cell disease, excessive production of blood cells in the bone marrow causes bones to grow abnormally, resulting in long legs and arms or misshapen skulls. Sickling that blocks oxygen to the bone can also cause bone loss and pain. Sickling that affects the hands and feet of children causes a painful condition called hand-foot syndrome. A condition called avascular necrosis of the hip occurs in about half of adult sickle cell patients when oxygen deprivation causes tissue death in the bone. Eventually adult patients may require surgery to remove diseased and dead bone tissue. Joint replacement may be required in severe cases. X-rays are not very useful for detecting early disease in the bones. MRI may be important.

Click the icon to see an image of the blood supply to bone.

Leg sores and ulcers occur in up to 10% of sickle cell patients and usually affect patients older than 10 years.

Women with sickle cell disease who become pregnant are at higher risk for complications, but serious problems have dropped significantly over the past decades. One study reported a higher risk for premature birth and low birth weight in the baby, and a higher risk for infections and hospital visits in the mother after delivery. Pain crises occurred in nearly half of the women, and nearly 60% required transfusions. The study also reported, however, that, in general, the outcome for pregnancy is favorable. Still, pregnancy during sickle cell is high-risk and carries a mortality rate of about 1%.

Older children and adult patients with sickle cell are subject to other medical problems, including impaired physical development, gum disease, and scarring and detachment of the retina.

Treatment

Research is ongoing toward identifying the biologic and chemical activities that promote or protect against the sickle cell process. Currently, experimental treatments focus on the basic processes that cause the red blood cells to sickle in the first place. There are three basic modes of treatment:

Stimulation of production of healthy fetal hemoglobin in order to inhibit the sickling process
Blocking dehydration in the cells
Transplantation of bone marrow or stem cells from healthy donors so that normal hemoglobin is produced rather than hemoglobin S

Hemoglobin F (HbF), also called fetal hemoglobin, is the form of hemoglobin in the fetus and small infants. Most HbF is later replaced by the hemoglobin that is present in the growing child and adult, although some HbF may persist. Fetal hemoglobin is able to block the sickling action of red blood cells so that infants with sickle cell disease do not develop symptoms of the illness while they still have hemoglobin F. Adults who have sickle cell disease but still retain high levels of hemoglobin F generally have mild disease.

Studies now suggest that the severity of sickle cell disease can be reduced by using drugs that stimulate production of HbF. Even increases as modest as 4% may have significant benefits for these patients.

Hydroxyurea. Hydroxyurea (Droxia, Hydrea) destroys cells in the bone marrow, which results in an increase in special cells that can produce HbF. It is currently the only drug in general use to prevent acute sickle cell crises.

Hydroxyurea is used to treat adults and adolescents with moderate-to-severe recurrent pain (occurring three or more times a year). Hydroxyurea reduces sickling crises and pain, priapism, the number of transfusions, and life-threatening complications in this group. The benefits appear to be long-lasting. Hydroxyurea is not a cure-all. Not all patients respond to hydroxyurea, and the best candidates for the treatment are not yet clear. Small studies have reported no protection from damage in the spleen or bones and joints. Effects on stroke and complications in the eye or kidney are not yet known.

Hydroxyurea is still being investigated in young people. To date, the response to the drug in children and teenagers with sickle cell disease is similar to the response in adults, and few severe adverse effects are being reported. Recent research also suggests that hydroxyurea is safe and beneficial for infants. A 2005 study indicated that long-term hydroxyurea treatment can improve height, weight, and spleen function, and reduce episodes of acute chest syndrome. Patients in the study started the treatment as babies, and most patients took the drug for at least 4 years. The drug was given by mouth in a flavored liquid form.

Side effects include gastrointestinal problems, headache, drowsiness, and skin and nail changes. In rare cases, there have been reports of hallucinations and seizures. The drug may also cause leg ulcers and gangrene in some patients. Patients should handle hydroxyurea with care and wash their hands before and after touching the bottle or capsules. Household members who are not taking hydroxyurea (such as caregivers) should wear disposable gloves when handling the medicine or its bottle.

Cytidine Analogues. Cytidine analogues increase HbF production by affecting the genes that regulate it. Decitabine is one such drug that was developed to treat leukemia and other blood malignancies. Early studies are suggesting that it significantly increases HbF production, even in patients in whom treatment with hydroxyurea failed. Only minor toxic side effects have been reported to date.

Butyrates. Butyrates are natural fatty acids, the end-products of fermented carbohydrates in the intestinal tract that are also metabolized from fiber. One derivative, arginine butyrate, has been under investigation for some time in sickle cell for its role in stimulating production of HbF. Because its actions are different from hydroxyurea, experts hope the two drugs may eventually be used in combination. However, arginine butyrate is difficult to administer, and different forms that might make it simpler to use are needed.

General Guidelines for Managing a Sickle Cell Crisis. The basic objectives for managing a sickle cell crisis are control of pain and rehydration by administration of fluids. Oxygen is typically given for acute chest syndrome. Effective pain medications are available to help reduce the severe pain of sickle cell crises.

Accurate and continually updated assessment of pain determined by patient input and participation is at the crux of effective care for children with sickle cell disease. Often, however, patients are not given the treatment they require.

Many patients, their families, and even doctors are hesitant to use opioids aggressively because of fear of addiction. This fear, however, is nearly always unwarranted. Addiction occurs in only about 1 - 3% of patients with sickle cell disease who are taking opioids.
Many patients use emergency rooms of large hospitals for treating acute pain. Waiting times are long, and there is no single health care provider who knows the patient and can offer consistent assessment and management of pain.
Many doctors do not understand the nature of sickle cell pain. For example, early phases of sickle cell crisis can cause severe pain before test results confirm a diagnosis of a crisis. In such cases, health professionals may question the patient's self-reporting and withhold appropriate pain medication.
Patients may behave normally (talking on the phone, sleeping) and not appear to be in pain, but have actually developed coping behaviors to allow them to function in spite of severe pain.
Children and adults report pain differently, with children tending to report less pain than they actually feel. (One way of determining the severity of pain that a child feels is to show pictures of faces demonstrating degrees of pain and asking the child to point to the one that best expresses his or her experience.)

Adult patients and parents of children with the disease should insist on aggressive pain-relief treatment. If doctors show any reluctance to administer medications after the onset of pain, patients or caregivers should not hesitate to seek a more responsive health care professional.

All patients should have a treatment plan that helps guide them and their families during a pain episode. Plans should outline which medicines to take and when to seek medical help. Patients and families should learn to recognize symptoms early and begin managing with an appropriate amount of pain medication.

Opioids. Severe pain should be treated with strong painkillers, usually opioids. Opioids are generally given orally to adults and adolescents and intravenously to children. Nevertheless, there are exceptions. Studies indicate that oral medications are also effective in children.

Morphine is often used for frequent or prolonged episodes of pain. Unfortunately, its effectiveness is not as long-lasting in sickle cell patients as it is in other patients with severe pain, such as those with cancer.
The opioid meperidine (Demerol) is also used for sickle cell crises. Meperidine is not as powerful as morphine, however, and, if used for prolonged periods, may cause twitches, tremors, and disturbed mental states including seizures.
Some newer synthetic opioids such as fentanyl (Duragesic) or hydromorphone(Dilaudid) have a rapid onset and possibly fewer side effects than morphine. Fentanyl can be applied using a patch, which may help some patients who have difficult receiving intravenous drugs. It takes 12 hours to be effective, however.
Oral drugs, such as methadone, oral morphine, codeine, and oxycodone, are useful for home management of chronic pain and for transitional treatments between the hospital and home. Tramadol (Ultram) is a potent oral painkiller that has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It may be very useful for sickle cell patients who need painkillers outside the hospital. It has minimal effects on respiratory function and has a low potential for addiction.

Possible side effects of opioids are vomiting and nausea, itching, constipation, itching, skin rashes, and problems urinating. If the patient vomits or becomes nauseated, the doctor may prescribe prochlorperazine (Compazine). Devices have been developed to allow patients to administer their own painkillers as needed.

Anti-Inflammatory Drugs. Because of the potentially serious side effects of opioids, doctors are constantly searching for safer and easier ways of reducing the severity of pain of sickle cell crises. Because experts believe that inflammation is a major contributor to the pain of sickle cell disease, drugs that reduce inflammation are being studied:

Prescription-strength NSAIDs include diflunisal (Dolobid) and ketorolac (Toradol). Ketorolac may be particularly helpful in relieving bone pain, and may be effective for individuals who cannot tolerate opioids. In one study, it was superior to meperidine and had fewer side effects. Studies have suggested, however, that when used as first-line therapy in an acute crisis, ketorolac is effective only in about half of episodes.
Corticosteroids are powerful anti-inflammatory drugs that are commonly used to treat pain caused by inflamed muscles and joints. Such drugs include methylprednisolone (Medrol) and dexamethasone (Decadron, Hexadrol). Studies suggest that using these drugs along with opioids may help some sickle cell patients. Because steroids can suppress the body's infection fighters, they should not be given to patients with bacterial infections or any serious medical complication.

Epidural Anesthesia. An epidural analgesia (injection of an anesthetic into the spinal fluid) may be very effective for pain that is unresponsive to the usual therapies.

Initial Management. Acute chest syndrome can be fatal and must be treated immediately. Basic treatments include the following:

Supplementary oxygen -- this is critical and life saving.
Administration of fluids -- overhydration should be avoided to reduce the risk of fluid in the lungs.
Pain relievers
Bronchoscopy (a diagnostic procedure involving insertion of a tube into the lower airways) may be needed to identify infection.

Other Treatments. Other treatments include:

High-dose intravenous corticosteroids (usually dexamethasone) may hasten recovery from acute chest syndrome and reduce the duration of hospitalization. They are also important if fat embolisms develop.
Antibiotics that specifically target the organisms ( Chlamydia, Mycoplasma) that commonly trigger acute chest syndrome. Such antibiotics include erythromycin, azithromycin, clarithromycin, and various tetracyclines.
Transfusions are important early on for rapid improvement in severe cases, especially if fat embolisms have developed.

To increase oxygen levels in children hospitalized for acute chest syndrome, a simple breathing technique known as incentive spirometry may also be beneficial. A spirometer is a hand-held plastic device commonly used by asthma patients to measure their lung capacity and by patients after surgery to increase intake of oxygen. Patients with sickle cell disease are asked to inhale and exhale into this device every 2 hours during the day and when wake at night until their chest pain subsided. This device forces more air into the lungs, and may help prevent the serious drop in oxygen levels and the risk for infection caused by acute chest syndrome. Spirometry leads to slower rates of collapsed lung tissue and infections. This very inexpensive and simple treatment might have beneficial long-term effects.

General Approach to Treating Infections. Fever in any sickle cell patient should be considered an indication of infection. Temperatures over 101°F in children warrant a call to the doctor. Adults with sickle cell should call the doctor if they have a have fever over 100°F and any signs of infection, including chest pain, productive cough, urinary problems, or any other symptoms. Some approaches for treating infections include:

Hospitalization for infections. When sickle cell patients develop infections, they are nearly always hospitalized immediately and treated with intravenous or high-dose injections of antibiotics in order to prevent septicemia, the dangerous spread of the infection throughout the body. Antibiotics called cephalosporins [cefotaxime (Claforan), ceftriaxone (Rocephin), or cefuroxime (Ceftin)] are typically used. Repeated hospitalizations are very disruptive for both children and adults. Studies have found that older children whose fever is below 38.5°C (101°F) and who have no serious infection or other complications may not need hospitalization. Children who have indications of serious complications of infection (higher fevers, pain, a history of pneumonia, and signs of dehydration) should remain in the hospital.
Treatment of osteomyelitis. If osteomyelitis, an infection in the bone, occurs, a 6-week antibiotic course is needed, most of it intravenous. An accurate diagnosis of osteomyelitis is sometimes difficult to make, because bone damage from sickling can cause similar symptoms. It should be strongly considered in children with signs of pain and swelling in the legs, a high white blood cell count, high fever, and high levels of a test that measures so-called sedimentation rates. It is important, however, to confirm the presence of an actual infection before administering antibiotics, because the antibiotic treatment required for osteomyelitis is so intensive and prolonged. The most common cause of osteomyelitis in children is Salmonella.
Treatment of urinary tract infections. Urinary tract infections may be difficult to manage and can be a serious problem for pregnant women with sickle cell disease. Doctors should take a urine culture before beginning antibiotic treatment and another culture 1 - 2 weeks after treatment to be sure the infection has cleared up.

Bosentan (an endothelin receptor antagonist) and other drugs are used to treat this condition. Investigational therapies include nitric oxide, L-arginine (which converts to nitric oxide), blood transfusions, warfarin, vasodilators, and sildenafil (Viagra). Hydroxyurea does not appear to help.

Folic acid and possibly iron supplements are often given to help treat the anemia that occurs in patients with sickle cell disease. (Patients who are given multiple transfusions may experience iron overload, and iron supplements should be avoided in such cases. Also, folic acid can mask pernicious anemia, which is caused by deficiency of vitamin B12 and is more common in African-Americans than other populations.)

Kidney damage in patients with sickle cell disease can cause bleeding into the urine. Mild episodes can usually be treated with bed rest and fluids. Severe bleeding may require transfusions. ACE inhibitors are drugs commonly used to control high blood pressure and are proving to be important for preventing hypertension and kidney failure in sickle cell patients. Such drugs include captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), and lisinopril (Prinivil, Zestril).

Priapism causes prolonged and painful erections that can last from several hours to days. It is best to relieve this problem within 12 hours. Relief within 36 hours is important to avoid permanent impotence. Pain relief and intravenous fluids are the initial steps. Exchange transfusions may be used to reduce the hemoglobin S and sickling that cause this condition. Drugs used to prevent priapism include terbutaline and phenylephrine, which help restrict blood flow to the penis. Hormonal treatments such as leuprolide (Lupron) and diethylstilbestrol may prevent repetitive and prolonged episodes of priapism in severely affected teenage boys with sickle cell disease. A surgical procedure that implants a shunt to redirect blood flow is sometimes performed. Inflatable penile implants may help maintain potency without causing priapism. Researchers are also investigating other treatments including inhaled nitric oxide, arginine, and sildenafil (Viagra).

The spleen is often removed (splenectomy) in children who have one or two acute splenic sequestration crises. Transfusion therapy is an alternative for preventing acute splenic sequestration in high-risk patients. At this time there are no studies comparing overall survival and benefits between the two approaches.

Leg ulcers are difficult to treat. Simple treatment with a moist dressing usually provides the best results. To treat mild ulcers, the leg should be gently washed with cotton gauze soaked in mild soap or a solution of one tablespoon of household bleach to one gallon of water. A dressing soaked in diluted white vinegar may be applied every 3 - 4 hours.

More severe ulcers require debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means. Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing. Topical antibiotics, saline or zinc oxide dressings, or cocoa butter or oil are also used depending on severity. The leg should be elevated. Bed rest for a week or more is sometimes required for severe ulcers.

Skin grafts and transfusions have been helpful in some extreme cases. In one promising study administering arginine butyrate for many weeks improved ulcer healing by 10-fold. (This drug is also under investigation for other beneficial effects in patients with sickle cell disease.)

Women who are pregnant should be treated at a high-risk clinic. They should take folic acid in addition to multivitamins and iron. Standard treatment is given for sickle cell crises, which may occur more frequently during pregnancy. The benefits of transfusions to prevent crises during pregnancy are not yet clear and experts recommend them only for women who experience frequent complications during pregnancy.

Women with sickle cell disease should talk to their doctors before becoming pregnant. Sexually active women should use contraception at all times.

At this time, the only true cure for sickle cell disease is bone marrow or stem cell transplantation. The bone marrow nurtures stem cells, which are early cells that mature into red and white blood cells and platelets. By destroying the sickle cell patient's diseased bone marrow and stem cells and transplanting healthy bone marrow from a genetically-matched donor, normal hemoglobin may be produced. Clinical studies using a few carefully selected patients have reported very successful results.

Up to 80 - 85% of patients who meet criteria for receiving a transplant receive remain disease free. Unfortunately, only about 7% meet the criteria for transplantation, including those who:

Are age 16 or younger (generally considered the better candidates, but patients in their 20s have had successful transplants)
Have severe symptoms but no long-term organ or neurologic damage
Have a genetically matched brother or sister who will donate their marrow

Complications. Bone marrow transplant carries its own dangers and limitations. About 10% of those who have bone marrow transplants die from the treatment. Some complications include:

In patients who do not receive a bone marrow donation from a matched sibling, the transplanted cells from a donor (called allogeneic grafts) may attack the patient's own tissues, a potentially fatal condition called graft-versus-host disease (GVHD). Drugs that destroy bone marrow and suppress immunity must be administered before the procedure so that the body's immune system does not attack the transplanted tissue. Still, this does not always prevent the problem.
Other very serious complications include bleeding, pneumonia, and severe infection.
Those who live but are not cured face long-term problems caused by the drugs used in transplantation and by the disease itself.
Even in those who are cured, long-term consequences may include a higher risk for cancer and infertility.

The use of umbilical cord blood and cells from placentas is showing promise for providing healthy stem cells to patients who do not have genetically matched donors for bone marrow transplant. Cord blood has certain advantages over stem cell transplantation, including the capacity to produce more cells quickly. Because immune factors in cord blood are immature, the risk and severity of graft-versus-host disease may be reduced.

Early clinical trials are also reporting some success with a process called partial chimerism, in which a mixture of the patient's and a donor's bone marrow is used. The procedure has far fewer side effects because all the bone marrow is not destroyed. Although some sickle blood cells remain, small studies indicate that the patients are still free of the typical infections and pain of the disease.

Transfusions are often critical for treating sickle cell disease. In some cases, they may be given on a regular basis to prevent stroke or other life-threatening complications of the disease. Ongoing transfusions can reduce episodes of pain and acute chest syndrome. They can also help improve height and weight in children with sickle cell disease. Regular transfusions, however, can have severe side effects. Normal hemoglobin levels for patients with sickle cell disease are around 8 g/dL. Doctors will try to keep the hemoglobin level no higher than 10 g/DL after transfusion.

Transfusions may be required by sickle cell patients either for specific episodes (used only for specific events) or as chronic transfusions (ongoing transfusions).

Episodic Transfusions. Episodic transfusions are needed in the following situations:

To manage sudden severe events, including acute chest syndrome, stroke, widespread infection (septicemia), and multi-organ failure.
To manage severe anemia, usually caused by splenic sequestration (dangerously enlarged spleen) or aplasia (halting of red blood cell production, most often caused by parvovirus). Transfusions are generally not required for mild or moderate anemia.
Before major surgeries. Some evidence suggests that a conservative transfusion regime is as effective as aggressive transfusions in these cases, but more research is needed. Transfusions are generally not required for minor surgeries.

Chronic Transfusions. Chronic (on-going) transfusions are used for:

Stroke Prevention. Chronic transfusions are also used to prevent first or recurrent strokes. Evidence shows that regular (every 3 - 4 weeks) blood transfusions can reduce the risk of a first stroke by 90% in high-risk children. The objective of such transfusions is to reduce hemoglobin S concentrations to less than 30% of total hemoglobin. In addition, studies indicate that as many as 90% of patients who have experienced a stroke do not experience another stroke after 5 years of transfusions. In 2004, the National Heart, Lung, and Blood Institute (NHLBI) issued a clinical alert strongly advising doctors against terminating regular transfusions for high-risk children.
Pulmonary hypertension and chronic lung disease
Heart failure
Chronic kidney failure and severe anemia
Unusually severe and protracted episodes of pain

Chronic blood transfusions carry their own risks, including iron overload, alloimmunization (an immune response reaction), and exposure to bloodborne pathogens. Still, data from large-scale trials suggest that the risks for stroke outweigh the risks associated with transfusions. Researchers are working on ways to reduce the side effects associated with transfusion treatment.

Kinds of Transfusions. Transfusions may be either simple or exchange.

Simple Transfusion. Simple transfusions involve the infusion of one or two units of donor blood to restore blood volume levels and oxygen flow. It is used for moderately severe anemia, severe fatigue, and nonemergency situations when there is a need for increased oxygen. It is also used for acute chest syndrome.
Exchange Transfusion. Exchange transfusion involves drawing out the patient's blood while exchanging it for donor red blood cells. It can be done as manual procedure or as automatic one called erythrocytapheresis. Exchange transfusions should be used promptly if there is any evidence that the patient's condition is deteriorating. It prevents stroke and also may be used in patients with severe acute chest syndrome and to reduce the risk of iron overload in patients who require chronic transfusion therapy. Studies suggest that it may improve oxygenation and reduce hemoglobin S levels. Exchange transfusion may also reduce the risk of heart failure and help prevent fat embolism, a life-threatening condition in which fatty tissue from the bone marrow travels to blood vessels in the lungs and cuts off oxygen.

Iron Overload and Chelation Therapy. Iron overload increases risk for complications, including liver cancer and heart failure. A liver biopsy accurately determines whether excess iron levels are present. A non-invasive test called a superconducting quantum interference device (SQUID) should be used if available.

Chelation therapy is used to remove excess iron stores in the body that can harm the liver, heart, and other organs. The drug deferoxamine (Desferal) is commonly used during such therapy. Unfortunately, deferoxamine has some severe side effects and must be used with a pump for about 12 hours each day. Many patients do not continue treatment. In 2005, the drug deferasirox (Exjade) was approved for the treatment of transfusion-related iron overload in patients ages 2 and older. It is taken once a day by mouth. Patients mix the pills in liquid and drink the mixture. This new treatment may make chelation therapy much easier and less painful for patients.

Other Complications of Transfusion Therapy.

Immune reactions. An immune reaction may occur in response to donor blood. In such cases, the patient develops antibodies that target and destroy the transfused cells. This reaction, which can occur 5 - 20 days after transfusion, can result in severe anemia and may be life-threatening in some cases. It can be generally prevented with careful screening and matching of donor blood groups before the transfusion.
Hyperviscosity. With this condition, a mixture of hemoglobin S and normal hemoglobin causes the blood to become sticky. The patient is at risk for high blood pressure, altered mental status, and seizures. Careful monitoring can prevent this condition.
Transmission of viral illness. Before widespread blood screening, transfusions were highly associated with a risk for hepatitis and HIV. This complication has decreased considerably.

Nitric oxide, a soluble gas, is a natural chemical in the body that relaxes smooth muscles and expands blood vessels. Hemoglobin removes nitric oxide. Because sickle cells release hemoglobin, patients with the disease are deficient in nitric oxide. This lack of nitric oxide constricts blood vessels and causes pain in sickle cell diseases. In adult patients, men may be more susceptible to this effect than women. Some studies indicate that inhaling nitric oxide may slow the disease process and improve symptoms in acute sickle cell crises. It is difficult to administer, however. More studies are needed. (Nitric oxide is not the same substance as nitrous oxide, the so-called laughing gas used in dentistry.)

Sickle cell disease can cause red blood cells to break apart. This process is called hemolysis. Hemolysis causes a lack of the amino acid arginine. Arginine is involved in producing nitric oxide. Recent research suggests that a lack of arginine may contribute to the development of pulmonary hypertension, a leading cause of death in patients with sickle cell disease. Pulmonary hypertension causes high blood pressure in the arteries that carry blood to the lungs.

A 2005 study found that patients with sickle cell who had low levels of arginine were 3.6 times more likely to die than patients with high arginine levels. Most patients in the study died from pulmonary hypertension. Scientists are working on developing a blood test that could measure amino acid levels and help identify patients at greatest risk of death. They are also working on developing drugs that could block arginase, a protein in cells that is released during hemolysis, which consumes arginine. There is no evidence indicating that arginine nutritional supplements are helpful or harmful for patients with sickle cell disease. Patients should talk to their doctor before taking these or other supplements.

Researchers are studying the mechanisms behind cell membrane damage, dehydration, and potassium loss in order to develop drugs that will inhibit these processes. Drugs under investigation include those that specifically block the Gardos channel, which is an important route for potassium loss and dehydration. Researchers are also studying specific types of mineral supplements, such as magnesium pidolate and zinc sulfate. Initial studies have shown promising results for zinc’s efficacy in preventing red blood cell dehydration, but more research is needed.

Prevention and Lifestyle Changes

No o proven methods prevent either sickle cell crises or long-term complications of sickle cell disease. By taking precautions and aggressively managing problems that occur, however, patients are now living longer, with a better quality of life.

To prevent or reduce the severity of long-term complications, a number of precautions may be helpful:

Have regular physical examinations every 3 - 6 months.
Have periodic and careful eye examinations.
Have sufficient rest, warmth, and increased fluid intake. (These are critical precautions for reducing oxygen loss and the risk for dehydration.)
Avoid conditions, such as crowds, that increase risk for infections.
Avoid excessive demands on the body that would increase oxygen needs (physical overexertion, stress). Low impact exercise (leg lifts, light weights) may be useful and safe for maintaining strength, particularly in the legs and hips, but patients should consult their doctor about any exercise program.
Avoid high altitudes if possible. If flying is necessary, be sure that the airline can provide oxygen.
Do not smoke, and avoid exposure to second-hand smoke. Both active and passive smoking may promote acute chest syndrome in patients with sickle cell disease.

Vaccinations. Everyone with sickle cell disease should have complete regular immunizations against all common infections. Children should have all routine childhood vaccinations. The following are important vaccinations for everyone with sickle cell disease:

Pneumococcal vaccines. All sickle cell patients should be vaccinated with the pneumococcal vaccine. There are two types of pneumococcal vaccines; the choice between them depends on the age of the patient. Infants and children less than 2 years of age should receive 4 doses of the pneumococcal conjugated vaccine (Prevnar) between 2 - 15 months of age. (This vaccine has helped reduce the rate of serious pneumococcal disease by more than 90%.) The pneumococcal polysaccharide vaccine should be administered at age 2 years or older, repeated after 3 - 5 years for patients younger than age 10, or in 5 years for patients older than age 10.
Vaccination against Haemophilus influenza, the major cause of childhood meningitis, starting at age 2 months.
Influenza vaccines should be given every winter, starting at age 6 months.
Meningococcal vaccination for patients age 5 and older.
Hepatitis B vaccine. Anyone starting transfusion therapy should receive this vaccine.

Tuberculosis skin testing should be performed every year.

Antibiotics. In addition to regular immunizations, preventive (prophylactic) antibiotics are the best approach for protection against pneumonia and other serious infections among children with sickle cell disease. Babies diagnosed with sickle cell are given daily antibiotics, starting at 2 months of age and continuing through 5 years of age. Penicillin is usually the antibiotic given, unless a child is allergic to it.

Many patients stop taking their antibiotics or the parents stop giving them to their children. Doctors are concerned about developing bacterial resistance to common antibiotics and researchers warn that patients might experience breakthrough infections as resistance becomes more frequent.

Foods. Good nutrition, while essential for anyone, is critical for patients with sickle cell disease. Some dietary recommendations include:

Fluids are number one in importance. The patient should drink as much water as possible each day to prevent dehydration.
Diet should provide adequate calories, protein, fats, and vitamins and minerals. Patients and families should discuss vitamin and mineral supplements with their doctors and nurses.
Studies on omega-three fatty acids, found in fish and soybean oil, suggest that they might make red blood cell membranes less fragile, and possibly less likely to sickle, although no studies have proven this definitively. Fish and soy products have health benefits in any case. In one small study, fish oil supplements reduced the frequency of painful episodes over the course of a year.

Vitamins. Patients should take daily folic acid and vitamin B12 and B6 supplements. Vitamin B6 may have specific anti-sickling properties. Some experts recommend 1 mg folic acid, 6 microgram vitamin B12, and 6 mg vitamin B6. Foods containing one or all of these vitamins include meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast. Of note, folic acid can mask pernicious anemia, which is caused by deficiency of vitamin B12 and is more common in African-Americans than other populations.

Click the icon to see an image of vitamin B6 sources.

Note on Iron. Although sickle cell disease is often referred to as anemia, patients should avoid iron supplements or iron rich foods when receiving multiple transfusions, which increase the risk for iron-overload.

In assessing the seriousness of this disease, no one should underestimate its emotional and social impact. For the family, nothing is more heartbreaking than watching their child endure extreme pain and life-threatening medical conditions. The patient endures not only the pain itself but also the emotional strain from unpredictable bouts of pain, fear of death, and lost time and social isolation at school and work. Academic grades among patients average less than C, even in children with a low frequency of hospitalization (averaging 17 days a year).

These problems continue over the years, and both children and adults with sickle cell disease often suffer from depression. The financial costs of medical treatments combined with lost work can be very burdensome.

Any chronic illness places stress on the patient and family, but sickle cell patients and caregivers often face great obstacles in finding psychological support for the disease. Communities in which many sickle cell patients live generally lack services that can meet their needs, and professionals who work in their medical facilities are often overworked. In a study comparing patients with different kinds of long-term illnesses, those with sickle cell disease gave the lowest scores to their doctors and other professional caregivers for compassion, and were least satisfied with their medical care.

It is very important for patients and their caregivers to find emotional and psychological support. No one should or can endure this life-long disease alone. Unfortunately, studies indicate that most patients do not receive even basic supportive care that could help reduce the anxiety and intensity of pain that occurs when a sickle cell crisis erupts.

The following are some measures that some people find helpful in dealing with this disease:

Stress Reduction. Stress reduction techniques and relaxation methods appear to be helpful. Breathing and mediation techniques may be very helpful.
Cognitive-Behavioral Therapy. Studies suggest that cognitive behavioral therapies that teach coping skills can result in less negative thinking and even less pain. Coping skills refer to the patient's ability to respond to symptoms, such as pain.
On-Line Support Help. Computer on-line services are now valuable sources of support groups and access to research. They are particularly valuable for patients who cannot easily leave home or for patients who are ill.
Support Associations. Parent and professional support associations still offer the best and least expensive sources of help.

Other important factors are those that help maintain positive attitudes including spirituality, humor, or having important life goals (such as having children or pursuing a career).

Resources

www.sicklecelldisease.org -- Sickle Cell Disease Association of America
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute (NHLBI)
www.scinfo.org -- Sickle Cell Information Center
www.sicklecellsociety.org -- Sickle Cell Society (UK)
www.sicklecell-info.org -- NHLBI Comprehensive Sickle Cell Centers
www.clinicaltrials.gov -- Find clinical trials

References

Adams RJ, Brambilla D; Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) Trial Investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005 Dec 29;353(26):2769-78.

Al Hajeri AA, Fedorowicz Z, Omran A, Tadmouri GO. Piracetam for reducing the incidence of painful sickle cell disease crises. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD006111.

Bernaudin F, Socie G, Kuentz M, et al Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007 Oct 1;110(7):2749-56. Epub 2007 Jul 2.

Dunlop RJ, Bennett KC. Pain management for sickle cell disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003350.

Fathallah H, Atweh GF. Induction of fetal hemoglobin in the treatment of sickle cell disease. Hematology Am Soc Hematol Educ Program. 2006:58-62.

Halasa NB, Shankar SM, Talbot TR, et al. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis. 2007 Jun 1;44(11):1428-33. Epub 2007 Apr 18.

Hankins JS, Wynn LW, Brugnara C, Hillery CA, Li CS, Wang WC. Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anemia. Br J Haematol. 2008 Jan;140(1):80-5. Epub 2007 Nov 7.

Lee MT, Piomelli S, Granger S, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood. 2006 Aug 1;108(3):847-52.

Mehta SR, Afenyi-Annan A, Byrns PJ, Lottenberg R. Opportunities to improve outcomes in sickle cell disease. Am Fam Physician. 2006 Jul 15;74(2):303-10.

Singh PC, Ballas SK. Drugs for preventing red blood cell dehydration in people with sickle cell disease. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003426.

Tanabe P, Myers R, Zosel A, et al. Emergency department management of acute pain episodes in sickle cell disease. Acad Emerg Med. 2007 May;14(5):419-25. Epub 2007 Mar 26.

U.S. Preventive Services Task Force. Screening for Sickle Cell Disease in Newborns: U.S. Preventive Services Task Force Recommendation Statement. AHRQ Publication No. 07-05104-EF-2, September 2007. Agency for Healthcare Research and Quality, Rockville, MD.

Review Date:
3/11/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (1/1/2008).

A.D.A.M. Copyright

adam.com

Benign prostatic hyperplasia

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights
Introduction
Symptoms
Causes of Benign Prostatic ...
Causes of Lower Urinary Tra...
Risk Factors
Complications
Diagnostic Tests
Treatment
Lifestyle Changes
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Self-Management for Benign Prostatic Hyperplasia (BPH)

Men who receive training in lifestyle and behavioral approaches may be able to successfully manage BPH without drugs or surgery, suggests a 2007 study in the British Medical Journal. Men in the study were trained to self-manage their lower urinary tract symptoms (LUTS), a condition that often accompanies BPH. Self-management approaches included limiting daily fluid intake, avoiding caffeine and alcohol, and urinating at least once every 3 hours.

Diet and BPH

Eating lots of fruits and vegetables, especially those high in beta-carotene and vitamin C, may help protect against BPH, suggests a 2007 study in the American Journal of Clinical Nutrition. Another study, published in Urology, indicated that high consumption of cereal, bread, eggs, and poultry may increase the risk of BPH.

High Intake of Zinc Increases BPH Risk

High doses of zinc supplements may increase the risk for urinary problems, especially for men, indicates a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc. In general, the upper limit for zinc supplements should not exceed 40 mg/day.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe LUTS, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Botox for BPH?

Botulinum toxin A (Botox) is being investigated as a treatment for BPH. In research presented at the 2007 meeting of the American Urological Association, men who had Botox injected into their prostate glands experienced symptom relief and improved quality of life for up to a year after treatment.

Introduction

Hyperplasia is a general medical term referring to excess cell replication. Benign prostatic hyperplasia (BPH), also called benign prostate hyperplasia, is a noncancerous growth of the prostate gland. It is the most common noncancerous form of cell growth in men and usually begins with microscopic nodules in younger men. BPH, however, is not a precancerous condition. Prostate cancer usually occurs in the outer area of the prostate, called the peripheral zone.

The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid that mixes with sperm to make semen. The urethra carries urine from the bladder and sperm from the testes to the penis.

As BPH progresses, overgrowth occurs in the central area of the prostate, called the transition zone, which wraps around the urethra (the tube that carries urine through the penis). This pressure on the urethra can cause lower urinary symptoms that have been the basis for diagnosing BPH. In 2000, an expert committee suggested that the impact of such symptoms on quality of life, including sexual activity, is also important in assessment of the disease.

Click the icon to see an image of BPH.

Description of the Prostate Gland. The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:

Glandular cells, which produce a milky fluid that liquefies semen.
Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen. Molecules called alpha adrenergic receptors stimulate the muscle cells.
Stromal cells (which form the structure of the prostate).

Click the icon to see an image of the male reproductive anatomy.

The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

Functions of the Prostate Gland. The prostate gland provides the following functions:

The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
The prostate also secretes another substance that may have antibacterial properties.
The prostate gland also contains an enzyme called 5 alpha-reductase that converts testosterone to dihydrotestosterone, another male hormone with a major impact on the prostate.

Changes During the Lifespan. The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly. It reaches normal adult size and shape, about that of a walnut, when a man is in his early 20s. The gland generally remains stable until about the mid-40s, when, in most men, the prostate begins to grow again through a process of cell multiplication.

Hormonal changes also occur in the prostate gland. Testosterone levels fall while dihydrotestosterone remain at normal levels.

Symptoms

The symptoms commonly associated with BPH are collectively called lower urinary tract symptoms (LUTS). BPH is not always the cause of these symptoms. An enlarged prostate may be accompanied by few symptoms, while severe LUTS may be present with normal or even small prostates and are most likely due to other conditions. Many experts are now categorizing LUTS as either voiding or storage symptoms to help define the source of the problem.

Voiding symptoms, also referred to as obstructive symptoms, can be caused by an obstruction in the urinary tract. They are often due to BPH. Obstruction is the most serious complication of BPH and requires medical attention. Voiding symptoms include:

Weak or intermittent urinary stream
Straining when urinating
A hesitation before urine flow starts
A sense that the bladder has not emptied completely
Dribbling at the end of urination or leakage afterward
Painful urination
Hematuria (blood in the urine)

Storage symptoms, also referred to as irritative symptoms, include:

An increased frequency of urination, particularly at night
An urgent need to urinate
Bladder pain or irritation when urinating

Urine flows from the kidney through the ureters into the urinary bladder where it is temporarily stored. As the bladder becomes distended with urine, nerve impulses from the bladder signal the brain that it is full, giving the individual the urge to void. By voluntarily relaxing the sphincter muscle around the urethra, the bladder can be emptied of urine. Urine then flows out through the urethra.

The process of urination is more complicated than it appears:

It begins when waste fluids flow out of the kidneys into two long tubes called ureters.
The ureters empty into the bladder, which rests on top of the pelvic floor, a muscular structure similar to a sling running between the pubic bone and the base of the spine.
The brain regulates muscles in the urinary tract through a pathway of nerves. As the bladder fills to its capacity of 8 - 16 oz of fluid, the nerves send signals from the bladder to the brain that indicate how full the bladder is.
As the bladder swells, the muscles contract to prevent urination.
At the time of urination, the spinal cord initiates the voiding reflex. The detrusor muscles (which surround the bladder) contract, while the internal sphincter (a strong muscle encircling the neck of the bladder) relaxes.
When the internal sphincter is open, urine flows out of the bladder into the urethra (the tube that carries urine from the bladder out through the penis).

Causes of Benign Prostatic Hyperplasia

The causes of benign prostatic hyperplasia are not fully known. Several theories have been proposed to explain benign cell growth in older men.

Male Hormones. Androgens (male hormones) most likely play a role in prostate growth. The most important androgen is testosterone, which is produced throughout a man's lifetime. The prostate converts testosterone to a more powerful androgen, dihydrotestosterone (DHT). DHT stimulates cell growth in the tissue that lines the prostate gland (the glandular epithelium) and is the major cause of the rapid prostate enlargement that occurs between puberty and young adulthood. DHT is a prime suspect in prostate enlargement in later adulthood.

Estrogen. Some authorities believe that the female hormone estrogen may also play a role in BPH. (Some estrogen is always present in men.) As men age, testosterone levels drop, and the proportion of estrogen increases, possibly triggering prostate growth.

Another theory focuses on cells in a certain section of the gland that may become active late in life, signaling other prostate cells to replicate or causing them to be sensitive to growth-stimulating hormones.

This theory suggests that a process known as apoptosis, in which cells naturally self-destruct, goes awry and results in cell proliferation.

Some experts theorize that the blood vessels in the prostate gland may deteriorate as men age, causing abnormal blood flow and oxygen loss, which would stimulate cell growth. Such a theory is supported by the presence of heart and circulatory problems in many men with BPH.

Causes of Lower Urinary Tract Symptoms

Several structural or medical conditions, either independently or in conjunction with BPH, can cause lower urinary tract symptoms. In addition, prostate growth does not always explain symptoms normally attributed to BPH. Men with large prostates do not always have symptoms, and men with small or normal-sized prostates sometimes have symptoms that are more severe than in those with enlarged glands.

Abnormalities in the urinary tract can cause BPH-like symptoms in men with or without enlarged prostate glands. Such conditions can produce obstruction, impair or weaken the detrusor muscles surrounding the bladder, or cause other damage that impacts the urinary tract. They include:

Muscle contractions in the area where the bladder and urethra meet
A narrowing of the urethra
A weakened bladder
Overactivity in prostate muscles

The male and female urinary tracts are relatively the same except for the length of the urethra.

The process of aging weakens the detrusor muscles that surround the bladder, which causes the bladder to become unstable and lose capacity. Unstable detrusor muscles may also impair bladder storage capacity, which then produce irritative or storage symptoms. Studies also indicate that as men get older they may produce more urine at night, although the total daily output of urine is similar to that in middle-aged men. It is not fully known why this occurs.

Prostatitis is an inflammation of the prostate gland. It can be caused by bacterial infection, which is the easiest cause to diagnose. However, the most common form of prostatitis is nonbacterial.

Bacterial Prostatitis. A prostatitis infection can occur abruptly (acute) or be long-term (chronic). Chronic bacterial prostatitis (CBP) is often subtle and may persist for weeks or months with low-grade symptoms, including an urgent need to urinate, frequent urination, and the need to urinate at night. Pain may occur in the lower back or rectum, or it may develop after ejaculation. Because the prostate isn't swollen, doctors may mistake chronic prostatitis for BPH. A urine culture should always be taken, which, in the case of both acute and chronic bacterial prostatitis, will reveal bacteria and confirm a diagnosis. Antibiotics are required to treat CBP. Fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim, Septra) are particularly effective, but prolonged treatment may be necessary.

Nonbacterial Prostatitis. In nonbacterial prostatitis, inflammation occurs, but no bacteria are present. It is 8 times more common than bacterial prostatitis. The causes of nonbacterial prostatitis have not been determined. In one study, alfuzosin, an alpha-blocker drug that is used for BPH, provided some modest relief in patients with prostatitis and chronic pain. The routine use of drug therapy does not seem to help this condition. More research is needed.

Prostatodynia. Although it is considered a form of prostatitis, prostatodynia is a noninflammatory disorder characterized by prostate pain, but neither inflammation nor bacteria are present. The causes of prostatodynia are unknown.

Congestion of the prostate, sometimes called prostatosis, is a benign condition in which the prostate seems to be swollen by excess fluid. It can cause frequent, slow, or uncomfortable urination, but it responds well to a program of frequent ejaculation and sitz baths.

On occasion, prostate cancer can mimic BPH, since both conditions may cause obstruction of the urethra. Bladder cancer can sometimes cause urinary bleeding, frequency of urination, or a sense of urgency, also symptoms of BPH.

Click the icon to see an image of prostate cancer.

Several other conditions can impair the lower urinary tract, including tumors, reactions to medications, and spinal cord injuries. Diseases that affect the nervous system, such as diabetes, multiple sclerosis, and shingles, can desensitize the nerves so that they fail to sense fullness and do not trigger the contraction of the bladder.

Risk Factors

About 5.5 million American men have benign prostatic hyperplasia (BPH) that could warrant medical attention. Age is the major risk factor. BPH occurs in about 60% of men over 60 years of age and over 80% of men over age 80.

A family history of BPH appears to increase a man's chance of developing the condition. One study reported that men with BPH who had three or more family members with the condition had much larger prostate glands than men with BPH without such a family history.

Some evidence suggests a higher incidence of benign prostatic hyperplasia -- particularly fast-growing BPH -- in men with obesity, heart and circulatory diseases, and type 2 diabetes. Diabetes and hypertension, in any case, worsen urinary tract symptoms in men with BPH. In one study, diabetes adversely affected flow rates, although residual urine volumes were not significantly greater.

Complications

The progression of symptoms in benign prostatic hyperplasia (BPH) is typically very slow, and additional symptoms, when they occur, often come and go. Individual response to these symptoms also varies widely. Some men can tolerate very uncomfortable sensations of abnormal urination, while other men seek relief from mild symptoms. BPH does not appear to impair sexual function. Problems with urination, however, can be very distressing and severely affect quality of life in some cases.

Click the icon to see an animation about BPH.

Men are more apt to tolerate voiding symptoms (intermittent flow, hesitancy before urinating) and seek help for storage symptoms (urgency, frequency, urination at night). Voiding symptoms, however, may indicate an obstruction blocking the bladder, which if extensive can severely reduce urine flow and cause other complications, some serious.

Acute Urinary Retention. Sometimes a man is unaware of an obstruction until he suddenly cannot urinate at all. This condition is called acute urinary retention. It is a dangerous complication that can damage the kidneys and may require emergency surgery. In general, BPH progresses very slowly, and long-term urinary retention is very uncommon. Men with BPH at highest risk for this problem tend to be elderly and to have moderate-to-severe lower voiding symptoms. Taking anti-hypertensive drugs (except for diuretics) or antiarrhythmic drugs may also increase the risk.

Other Complications. Bladder obstruction can also cause bladder stones, blood in the urine, urinary tract infection, and incontinence. It may also increase the risk for chronic kidney disease. Unfortunately, no current tests can accurately predict which men are at higher risk for complications, although men with a weak urine stream and larger prostates are at higher risk for urinary retention.

Click the icon to see an image of prostate cancer.

Debate is ongoing over whether BPH and prostate cancer have any association. Both occur in men in the same age groups, and BPH causes prostate enlargement. Most evidence finds no significantly higher risk for prostate cancer in men with BPH. For one reason, the two conditions develop in different parts of the prostate:

BPH occurs in the inner transition zone, while
Cancer tends to develop in the peripheral outer zone

A 10-year study found no higher risk for prostate cancer in men with BPH. Unsuspected prostate cancer is detected during surgery in about 15% of BPH patients, but the risk of this slow-growing cancer is high in all older men. Some estimates suggest that up to a third of men over age 50 have at least microscopic prostate cancer.

Still, there is some evidence that men with fast-growing BPH may be at higher than average risk for prostate cancer. This prostate condition is also associated with obesity, heart disease, and diabetes. Some experts suspect that insulin resistance may be the common factor in all of these conditions, including prostate cancer.

Diagnostic Tests

An indexing tool called the International Prostate Symptoms Score (IPSS) can help evaluate the key lower urinary tract symptoms. As opposed to laboratory tests or other objective tests, this scoring system measures the patient's own experience. The higher the score, the more severe the conditions. It is useful for many reasons:

The patient's score on this test gives a highly accurate assessment of the effect of lower urinary tract symptoms on the quality of a man's life.
It is a reasonable basis from which the patient and doctor can discuss treatment options.
The index is also often used to gauge treatment outcomes and may be a better indicator of success than objective tests, such as the measurement of the prostate gland or the rate of urine flow.

Limitations. The IPSS is useful only as a measure of symptom severity, and has the following limitations:

Other conditions can produce similar scores, so the test is not used as a diagnostic tool for BPH.
The index does not include other urinary symptoms, such as dribbling and incontinence or sexual health, that are important for quality of life. At the very least, the patient should have a frank discussion with his doctor if such symptoms are present and affect his life.
It also does not reflect regional or ethnic differences that can vary the responses to these symptoms.


Symptoms over past month	Never	Less than 1 time in 5	Less than half the time	About half the time	More than half	Almost always
Sensation that the bladder is not empty after urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to urinate within two hours of a previous urination	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to stop and start again several times while urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Have a weak urinary stream	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to strain to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Number of times during the night awakened by the need to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Circle appropriate number. Totals of 7 or less = mild symptoms; 8-19 = moderate; 20-35 = severe.

Other indexing systems, such as Symptom Problem Index (SPI) and the BPH Impact Index (BII), which gauge different quality-of-life and disease issues, are being used in addition to the IPSS to help assess the patient.

Digital Rectal Exam. The digital rectal exam is used to detect an enlarged prostate. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate to estimate its size and to detect nodules or tenderness. The exam is quick and painless, but embarrassing for some, and far from infallible. The test helps rule out prostate cancer or problems with the muscles in the rectum that might be causing symptoms, but it generally underestimates the prostate's size. It is never the sole diagnostic tool for either BPH or prostate cancer.

Other Physical Examinations. The doctor will usually press on and manipulate (palpate) the abdomen and sides to detect signs of kidney or bladder abnormalities. The doctor will also check for signs of anemia or swelling in the legs and arms. Certain procedures that test reflexes, sensations, and motor response may be performed in the lower extremities to rule out possible neurologic causes of bladder dysfunction.

To determine whether the bladder is obstructed, an electronic test called uroflowmetry measures the speed of urine flow. The test cannot determine the cause of obstruction, which can be due not only to BPH but possibly also to problems in the urethra, weak bladder muscles, or other causes.

The patient is instructed not to urinate for several hours before the test and to drink plenty of fluids so he has a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that the patient remains still while urinating to help ensure accuracy, and that he urinates normally and does not exert strain to empty his bladder or attempt to retard his urine flow.
Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend then that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for several reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.
The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

A urinalysis can detect signs of bleeding or infection. A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. Although urinary infection is uncommon in younger men, it occurs more frequently in older men, particularly those with BPH. A urinalysis also helps rule out bladder cancer.

To rule out prostatitis (infection or inflammation of the prostate gland), a simple test called the Pre and Post Massage Test (PPMT) is about 90% accurate. This test requires two cultures and microscopic examinations of urine samples, taken before and after massage of the prostate gland. To massage the prostate the doctor simply inserts a gloved finger into the rectum and presses several times on the prostate. The following results are indicated by findings on cultures after massage:

Category II prostatitis (Chronic bacterial). Bacteria are found on post-massage.
Category IIIA prostatitis (Inflammatory chronic pelvic pain syndrome). Leukocytes or other cells are found that indicate inflammation.
Category IIIB prostatitis (Noninflammatory chronic pelvic pain syndrome). No signs of inflammation or bacteria.

In men with symptoms, blood tests can measure a substance called serum creatinine, which is a marker for kidney trouble. Kidney problems exist in an average of 13.6% of BPH patients. Studies have reported rates as high as 30% and as low as 0.3%.

A PSA test measures the level of prostate-specific antigen (PSA) in the patient's blood. It is the standard screening test for prostate cancer. A PSA is recommended annually for all men over 50 years old and for men over age 40 who are at high risk for prostate cancer.

BPH itself can also raise PSA levels, but the test has generally been optional for men with suspected BPH. One 2000 study indicated that PSA levels may be good predictors of future prostate growth in men with BPH. In the study, men with the lowest PSA level groups (0.2 - 1.3 ng/mL) had prostate growth rates of only 0.7 mL per year while those in the high PSA groups (3.3 - 9.9) had growth rates of 3.3. mL per year. Other research has detected a specific molecular form of PSA, called BPSA because it may be a specific marker for BPH. Such findings could eventually lead to a shift from focusing on symptoms and flow rates for diagnosis to a more specific and possibly preventive approach.

Certain treatments for BPH, including the drug finasteride (Proscar) and the surgical procedure transurethral resection of the prostate (TURP), can reduce PSA levels and possibly mask the existence of prostate cancer.

A more recent test identifies so-called free PSA, which is found in lower levels when prostate cancer is present and in higher levels with benign prostate hyperplasia. This may be more accurate than total PSA, regardless of whether a man is taking finasteride or not.

One of the important tests for urinary incontinence is the postvoid residual urine volume (PVR), the amount of urine left after urination. Normally, about 50 mL or less of urine is left; more than 200 mL is a definite sign of abnormalities. Measurements in between require further tests. The most common method for measuring PVR is with a catheter, a soft tube that is inserted into the urethra within a few minutes of urination. PVR can also be measured using transabdominal ultrasonography.

Ultrasound of the prostate does not require a catheter and gives an accurate picture of the size and shape of the prostate gland. Ultrasound is very beneficial when planning surgery and determining treatment options and gauging their effectiveness. Ultrasound may also be used for detecting kidney damage, tumors, and bladder stones. Ultrasound tests of the prostate generally use one of two methods:

Transrectal ultrasonography (TRUS) uses a rectal probe for assessing the prostate. TRUS is significantly more accurate for determining prostate volume. It can sometimes detect cancer.
Transabdominal ultrasonography uses a device placed over the abdomen. It can give an accurate measure of postvoid residual urine and is less invasive and expensive than TRUS.

Filling cystometry, also called cystometrography, is usually used for patients who cannot urinate and in whom nerve damage or injury of the bladder is suspected. The test is used to determine the absence or presence of a condition called uninhibited detrusor contractions (UDC), which often occurs in men with storage urinary tract symptoms. The detrusor is the group of muscle fibers that cover the outside of the bladder. The test does not add much information to results from less invasive tests and is not used routinely.

A urethrocystoscopy, also called cystourethroscopy, may be performed in men diagnosed with BPH, particularly if they are surgical candidates or if other urinary tract problems are suspected. Such problems include blood in the urine, infection, interstitial cystitis, bladder cancer, or prior surgery or injury. The doctor can determine the presence of a number of structural problems, including enlargement of the prostate, obstruction of the urethra or neck of the bladder, anatomical abnormalities, or the presence of stones.

Procedure. In this procedure, a flexible or rigid fiberoptic tube (an endoscope) is inserted into the urethra to allow doctors to view the lower urinary tract.

Complication. The procedure is not without risks. Complications are uncommon but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

An x-ray called an intravenous excretory urography (IVU) is an invasive test that is used only when complications in the upper urinary tract, particularly in the kidney, are suspected. Alternatively, an abdominal ultrasound plus a normal x-ray may be as useful as IVU for most patients with suspected upper urinary tract problems.

Complications and Side Effects. If there is any danger of kidney failure, the test should not be performed, since it can exacerbate the condition. Severe side effects of the test occur in 0.1% of patients.

Some doctors believe that a number of men may be incorrectly diagnosed with BPH when they have interstitial cystitis (an inflammation of the bladder that may be associated with allergic or autoimmune response). The potassium sensitivity test is sometimes used to diagnose IC. Some experts believe this test missed too many IC patients, although a 2001 study concluded that a combination of potassium sensitivity and urodynamic tests is useful in distinguishing between BPH and interstitial cystitis.

Treatment

Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:

Watchful Waiting. Watchful waiting (also known as active surveillance) involves lifestyle changes and an annual examination. Even when choosing watchful waiting, an initial examination is critical to rule out other disorders.
Treatment Options. The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms. Many options are available. They include drug therapies, minimally invasive procedures, and major surgery.

The choice between watchful waiting and treatment usually depends on a number of factors, such as urine flow rates, prostate size, and PSA levels. Men with BPH who develop symptoms at around age 50 are more likely to need treatment within their lifetimes than older men. Unfortunately, there is no current way to determine who specifically might be at risk for serious problems and need early treatment.

The development of the International Prostate Symptoms Score (IPSS) has made the evaluation of symptoms somewhat easier. This scoring service serves as a benchmark for determining severity. The decision to treat or not to treat is typically based on the guidelines described below, but the ultimate choice is often guided primarily by a man's perception of his own symptoms.

Mild, or No, Symptoms. Men with mild, or no, symptoms (IPSS scores of 7 or below) usually choose watchful waiting even if their prostates are enlarged. BPH eventually progresses to the point of needing treatment in about 15% of men with mild symptoms who wait.

Moderate Symptoms. The choice is most difficult for men with moderate symptoms (scores between 8 - 19) and may simply depend on a man's ability to tolerate them. Some studies have reported that up to 40% of men with moderate symptoms eventually seek treatment, and a quarter require surgery. In a small percentage of patients, symptoms improve.

Severe Symptoms. Men with severe symptoms (scores over 20) nearly always choose treatment, although if their prostate glands are small or normal-sized, symptoms may improve.

If a man opts for treatment, there are several choices. Most experts recommend a staged approach as follows:

Mild Symptoms. Medications are the best choice for men with mild symptoms who decide to have their condition treated. There are two standard choices: alpha-blockers and anti-androgens, nearly always finasteride (Proscar). Specific conditions determine the choice, although most men take an alpha-blocker. Men with mild symptoms who choose surgery only experience minor improvement afterward but face the same risks as patients with more severe symptoms.
Moderate-Severe-Symptoms. Men with moderate-to-severe symptoms often respond to the same medications as men with mild symptoms. (Combinations of alpha-blockers and finasteride are under investigation.) Recent developments in drug therapy have reduced the number of surgical procedures needed and delayed their use. However, a quarter of men with moderate symptoms, and even more men with severe symptoms eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are gaining prominence.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

The most common reason for choosing surgery is obstruction of the bladder outlet, which causes urinary retention. Surgery is also typically a reasonable option when BPH is clearly related to one or more of the following conditions:

Recurrent urinary tract infection.
Hematuria (blood in the urine). Studies have suggested that when hematuria is left untreated, two-thirds of patients continue to bleed and one third require surgery. The drug finasteride may help some men with this condition and should probably be tried before surgery.
Bladder stones.
Kidney problems.
Some experts believe that surgery might benefit patients for whom an early diagnosis of prostate cancer is important. Unsuspected prostate cancer is detected during surgery in about 15% of cases.

The greatest improvements resulting from surgery are usually increased urinary flow and reduced urine retention. In one study, men who chose surgery reported more worry and depression before the procedure, but afterward they had less depression and anxiety than those who had chosen medication. Often, however, the benefits of surgery are not permanent.

Lifestyle Changes

Certain lifestyle changes can help relieve symptoms and are particularly important for men who choose to avoid surgery or drug therapy. A 2007 study found that men who were educated on behavioral and lifestyle management of BPH were less likely to require surgery or drug therapy. Men should limit daily fluid intake to less than 2,000 mL (about 2 quarts) and, in particular, avoid alcohol and caffeine intake. Men should try to urinate at least once every 3 hours. “Double-voiding” may also be helpful -- after urinating, wait and try to urinate again. Cold weather and immobility may increase the risk for urine retention. Keeping warm and exercising may be useful. Stress reduction techniques may also help.

Studies have suggested the following:

Avoid fluids after your evening meal.
Coffee has been associated with a higher risk for BPH. Some evidence suggests that drinking green tea, however, may benefit the prostate.
Moderate alcohol consumption may be protective. (Heavy alcohol consumption, however, may increase the risk for lower urinary tract symptoms, and, in any case, is harmful.)
Genistein, a chemical found in soy, reduced the growth of BPH tissue in the laboratory. Although Asians have a low incidence of BPH and prostate cancer and also have diets rich in soy, it is not yet known if eating soy products will reduce the risk of BPH or improve any symptoms.
Fruits and vegetables rich in beta-carotene and vitamin C may help protect against BPH. Conversely, high consumption of cereals, bread, eggs, and poultry may increase the risk for BPH.
High doses of zinc supplements may increase the risk of BPH.

Decongestants and Antihistamines. Men with BPH should avoid, if possible, the many medications for colds and allergies that contain decongestants, such as pseudoephedrine (Sudafed). Such drugs, known as adrenergics, can exacerbate urinary symptoms by preventing muscles in the prostate and bladder neck from relaxing to allow urine to flow freely. Antihistamines, such as diphenhydramine (Benadryl), can also slow urine flow in some men with BPH.

Diuretics. Men who are taking diuretics, which increase urination, may want to talk to their doctor about reducing the dosage or switching to another drug. These are important drugs for many people with high blood pressure, with a proven track record for saving lives. No one should go off these medications without medical supervision.

Other Drugs. Other drugs that may worsen symptoms are certain antidepressants and drugs used to treat spasticity.

Some, but not all, research suggests that moderate exercise can reduce urinary tract problems associated with BPH.

Kegel (pelvic floor muscle) exercises, first developed to help women with childbirth, can also help men prevent urine leakage. They strengthen the pelvic floor muscles that both support the bladder and close the sphincter.

Performing the Exercises. Since the muscle is internal and sometimes hard to isolate, doctors often recommend practicing while urinating:

The patient is asked to contract the muscle until the flow of urine is slowed or stopped. He attempts to hold each contraction for 20 seconds.
He then releases the contraction.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Medications

The two primary drug classes used for BPH are:

Alpha-blockers. These drugs relax smooth muscles, especially in the urinary tract and prostate. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Uroxatral). Alpha-blockers help relieve BPH symptoms, but they do not reduce the size of the prostate. The can help improve urine flow and reduce risk of bladder obstruction. They are often the first choice, especially for men with smaller prostates.
5-alpha-reductase inhibitors. Finasteride (Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone, the male hormone that stimulates the prostate. These drugs are better for men with significantly enlarged prostates. In addition to relieving symptoms, they increase urinary flow and may even help shrink the prostate. However, patients may have to take these drugs for up to 6 - 12 months to achieve full benefits.

Because these two types of drugs work in different ways, researchers are investigating combinations of the two for selected patients. Results from the Medical Therapy of Prostatic Symptoms (MTOPS) trial, published in 2003, reported that a combination of doxazosin and finasteride delayed progression of BHP more effectively than either drug alone. The combination treatment may work best for high-risk patients with larger prostate glands and higher PSA readings. Many men, however, can control their condition with a single drug.

General Guidelines for Alpha-Blockers.Alpha-adrenergic antagonists, commonly called alpha-blockers, were originally used to treat high blood pressure. They are prescribed for BPH to relax smooth muscles in the prostate. The muscle cells in the prostate are stimulated by molecules called alpha adrenergic receptors. This can cause lower urinary tract symptoms.

Drugs that block these receptors relax the muscles in and around the prostate, increase urinary flow and improve symptoms, sometimes significantly. Improvement occurs within days to weeks. Because these drugs are short-acting, symptoms return very quickly once a man stops taking the medication. They neither affect PSA levels nor shrink the size of the prostate. Research also indicates that they may even promote a natural process called apoptosis, in which cells in the prostate gland self-destruct. Investigators are studying whether these drugs may help prevent the development of prostate cancer.

Alpha-blockers are prescribed for most men with BPH symptoms whose prostates are not significantly enlarged. Even men with moderately enlarged prostates might try alpha-blockers before more intense treatments because these drugs work fairly quickly, have no effect on sexual drive, and are the least expensive treatment for BPH. Some experts now recommend alpha-blockers as first-line treatment for patients with moderate-to-severe symptoms.

These drugs are generally referred to as either nonselective or selective alpha-blockers. Drugs in both categories are similar in effectiveness for reducing symptoms and improving urinary flow. There are some differences, however. Patients should discuss the appropriate alpha-blocker for their individual condition with their doctors.

Nonselective Alpha-Blockers. Nonselective alpha-blockers (also referred to as alpha-specific antagonists) include terazosin (Hytrin), doxazosin (Cardura), and alfuzosin (Uroxatral). Alfuzosin is the newest drug and can be taken once a day. They relax all smooth muscles, not only in the prostate but also those that surround any blood vessel in the body. These drugs work within a few weeks, are inexpensive, and produce long-lasting benefits. Alfuzosin begins to improve urine flow within hours.

Side Effects. Nonselective alpha-blockers can reduce blood pressure, which may cause dizziness, headache, rapid heartbeat, and fatigue. Orthostatic hypotension, a sudden drop in blood pressure when standing, can occur and increases the risk of falling. Taking the medication close to bedtime can help reduce these side effects. (Alfuzosin's extended-release formulation appears to pose a much lower risk than the other drugs.) Alpha-blockers can also cause headache, sore throat, and weakness. Nasal congestion occurs in about 2% of cases. Men may also experience a decreased ejaculate. (Impotence is not a common side effect of alpha-blockers, as it is with finasteride.)
Long-Term Effects. These drugs slow the progression of BPH but do not help prevent urinary retention.
Best Candidates. Nonselective alpha-blockers may be a good choice for many men with severe urinary problems and especially those with hypertension, high cholesterol levels, or both. However, alpha-blockers can exacerbate heart failure symptoms in men with this condition.

Selective Alpha-Blockers. Tamsulosin (Flomax) is the only selective alpha-blocker (sometimes called alpha1A-urospecific antagonists) approved for treatment of BPH. Naftopidil is a similar drug under investigation. These drugs target receptors that affect only the smooth muscles of the prostate. Tamsulosin seems to work as well as nonselective alpha-blockers. It is not clear if it reduces long-term complications of BPH.

Selective alpha-blockers appear to be very safe, even for years. Side effects are minimal. Most common ones include nasal congestion. The risk for low blood pressure and dizziness is lower than with the nonselective alpha-blockers. They may pose a higher risk for problems in ejaculation than nonselective alpha-blockers, but do not appear to cause impotence or reduce sexual drive as finasteride does. These drugs can interact with certain medications, including calcium channel blockers (particularly verapamil).

Researchers are studying the combination of tamsulosin and tolteridine (Detrol). Tolteridine is an anticholinerogic medication used to treat urinary incontinence. Tamsulosin targets the prostate while tamsulosin helps inhibit involuntary contractions of the bladder. A 2006 study in the Journal of the American Medical Association found that a combination of tolterodine and tamsulosin worked better than either drug alone for men with lower urinary tract symptoms (LUTS), including overactive bladder.

Specific Benefits. The prostate gland contains an enzyme called 5 alpha-reductase that converts testosterone to another androgen called dihydrotestosterone. Finasteride (Proscar) and dutasteride (Avodart), known as a 5-alpha-reductase inhibitors, block this enzyme and thus reduce dihydrotestosterone in the prostate.

Finasteride is not as effective as alpha-blockers in improving BPH and urinary tract symptoms, but it can be helpful. Follow-up studies have reported that the drug is safe and effective over the long-term. The 5 alpha-reductase inhibitors are perhaps most effective in reducing symptoms in men with large prostates. (Men with larger prostates and high PSA values may also benefit from combination therapy of finasteride and the alpha-blocker doxazosin.) In such cases, studies on finasteride also suggest it reduces the risk of acute urinary retention and the need for surgery. It also helps control bleeding in the urine that is related to BPH. A side benefit of finasteride is reduction of hair loss related to male hormones and in some cases hair growth in men with mild-to-moderate male pattern baldness.

Dutasteride (Avodart) is a newer drug that inhibits two types of the 5-alpha-reductase enzymes and achieves a more rapid suppression of dihydrotestosterone than finasteride. A 4-year study reported sustained improvements in urinary symptoms and prostate volume reduction. Comparison studies are needed to determine if the dual actions of dutasteride offer significant benefits over those of finasteride. Researchers are also investigating whether dutasteride can help prevent the development of prostate cancer.

Candidates. Some experts recommend 5-alpha-reductase inhibitors for men of any age who have all three of the following conditions:

Very large prostates (40 mL or larger)
Low urinary flow rates
Prostate enlargement related primarily to hormone-stimulated overgrowth of glandular tissue

Finasteride is also proving to be helpful for patients who have hematuria (blood in the urine) related to BPH.

Dosing. Finasteride and dutasteride are taken once a day. It may take as long as 6 - 12 months for a man to notice a change in symptoms.

Effects on PSA. Finasteride and dutasteride decrease prostate-specific antigen (PSA) levels, which are measured for screening prostate cancer. Lower PSA levels may mask the presence of the cancer. Doctors calculate PSA levels in men taking these drugs by doubling the PSA values. Studies confirm that this doubling equation helps provide an accurate measurement.

Side Effects. Finasteride has been associated with:

Sexual dysfunction, including low sexual drive and impotence, in about 6 - 19% of patients. Such problems appear to occur only during the first year of use and diminish over time in most men who take finasteride.
Reductions in energy.
Breast tenderness.
Possible weight loss in some men.

Other anti-androgens, including drugs known as gonadotropin-releasing hormone agonists, are effective against BPH, but they can reduce sexual drive and are much more likely to cause impotence. Flutamide is an anti-androgen that may be an alternative to surgery in certain patients with BPH who have physical or mental disorders.

Popular herbal treatments for BPH include:

Saw Palmetto. Saw palmetto is one of the most popular herbal remedies for BPH. It comes from the berry of the plant Serenoa repens. A major 2006 study in the New England Journal of Medicine found that saw palmetto had no benefit for treating BPH. The study enrolled 225 men with moderate-to-severe BPH. The men received either placebo or 160 mg of saw palmetto twice daily. After 1 year, there were no differences in symptom improvement between the placebo and saw palmetto groups.

Beta-Sitosterol. Beta-sitosterol preparations come from South African star grass, Hypoxis rooperi, and other plant species. Some studies have shown beta-sitosterol to improve urinary symptoms and flow. They may increase the risk for impotence, however.

Pygeum Africanum. The herbal Pygeum africanum is an extract from the bark of an African plum tree. In an analysis of 18 trials, the herb provided a moderate improvement in urinary symptoms compared to placebo. Side effects were mild. The studies were short in length, however.

Cernilton. Cernilton is prepared from rye grass pollen. Studies have been limited, but some suggest it may help improve symptoms, including nighttime urinary problems. Other studies have found no benefit.

Other popular herbs include nettle root extract (Urtica dioica) and pumpkin seed oil (Cucurbita peponis). There is no scientific evidence that any of these remedies help treat BPH.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.

Botulinum. Botulinum toxin A (Botox) injections, a common wrinkle treatment, cause small muscles to relax. This approach is now being investigated for treating many disorders that involve overexcited muscle activity, including BPH. Preliminary studies are showing promising results in improving urine flow and reducing urinary retention. Research, presented at the 2007 annual meeting of the American Urological Association, reported that men with BPH who had Botox injected directly into their prostate gland had symptom relief and improved quality of life for up to a year after treatment.

PDE5 Inhibitors. Phosphodiesterase-5 (PDE5) inhibitors can treat erectile dysfunction (ED). They include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Because lower urinary tract symptoms (LUTS) and ED often occur together in older men, researchers are investigating whether PDE5 inhibitors may help improve BPH symptoms. Research presented at the 2006 American Urological Association meeting suggested that sildenafil improves urinary symptoms in men who have both ED and LUTS. Another study indicated that a combination of sildenafil and the alpha-blocker alfusozin (Uroxatral) worked better for treating LUTS and ED than either drug alone.

Other Areas of Investigation. Researchers are looking at several different drugs for future BPH therapies. Most drugs being researched for BPH, such as arylpiperazines, target molecules in the prostate that may help suppress cell growth. Some efforts are focusing on drugs that affect the central nervous system or nerve fibers in the bladder and urethra to reduce urinary tract symptoms.

Other Treatments

Several surgical approaches are now available for treating BPH.

Invasive Procedures. The most effective surgical procedures, transurethral resection of the prostate (TURP) and open prostatectomy, are also the most invasive. They carry the highest risks for significant complications, including impotence and incontinence. Greater surgeon experience with TURP, however, has reduced complications and hospital stays. Because it is more effective than less invasive procedures, TURP remains the procedure of choice for many doctors. When considering invasive surgery, the patient should be sure his surgeon performs at least 50 of these procedures each year. The complication rates of the surgeon should be no higher than 1% for incontinence and 4% for impotence. Transurethral incision of the prostate (TUIP) is an alternative to TURP for men with smaller prostate glands.

Less Invasive Procedures. Minimally invasive procedures use some form of heat to destroy excess prostate tissue. The heat may be delivered by:

Radio frequency: transurethral needle ablation (TUNA)
Microwave: transurethral microwave thermotherapy (TUMT)
Electrical current: transurethral electrovaporization (TUVP)
Ultrasound: high-intensity focus ultrasound (HIFU)
Hot water: water-induced thermotherapy (WIT)
Laser: interstitial laser coagulation (ILC) and holmium laser enucleation of the prostate (HoLEP)

One laser procedure, photoselective vaporization (PVP), is typically done as an outpatient procedure. The patient goes home on the same day. However, there is no long-term data for this procedure.

None of the other minimally invasive procedures have proven superior to TURP to date, but they vary by complications. Some may be appropriate for certain patients, such as the following:

Younger men. (Many of the less invasive procedures carry a lower risk for impotence and incontinence than TURP, although the risk for TURP is not high.)
Debilitated elderly patients
Patients with severe medical conditions, including uncontrolled diabetes, cirrhosis, active alcoholism, psychosis, and serious lung, kidney, or heart disease
Men who are on blood-thinning drugs

Transurethral resection of the prostate (TURP) involves surgical removal of the inner portion of the prostate where BPH develops. It is the most common surgical procedure for BPH, although the number of procedures has dropped significantly over the past decades because of the availability of effective medications.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

Procedure. TURP usually requires a 1 - 3 day hospital stay. The surgeon inserts a fiberoptic endoscope, which is a thin tube, into the urethra. No incision is needed. The surgeon uses the endoscope to cut away excess prostatic tissue, and water solutions are used to flush away the excised matter.

Risk of Water Intoxication. If the fluids used during TURP build up, water intoxication can develop, which can be serious. This condition is referred to as the transurethral resection (TUR) syndrome and includes abdominal cramps, nausea, vomiting, lethargy, and dizziness. Patients who undergo TURP for longer than 1 hour and those with larger prostate glands seem to be at greater risk for this complication. An irrigation system that uses a mechanical valve may reduce the risk.

Postoperative Catheterization. A Foley catheter generally remains in place for 3 - 5 days after surgery to allow urination. This device is a tube inserted through the opening of the penis to drain the urine into a bag. The catheter can cause bladder spasms that can be painful, but they eventually cease.

Some studies have suggested that in selected patients the catheter can safely be removed within 24 - 48 hours, allowing patients to go home earlier. Early catheter removal is not appropriate for patients with intense urine retention, signs of infection, bleeding, or other complications.

Recuperation. Urine flow is stronger almost immediately after most TURP procedures. After the catheter is removed, patients often experience some pain or sense of urgency as the urine passes over the surgical wound. These sensations gradually subside. Complete healing takes about 2 months. The following are some tips for hastening recovery and avoiding complications:

During recuperation at home, the patient should avoid driving, operating heavy equipment, lifting, sudden movements, and straining the muscles in the lower tracts, such as during a bowel movement.
Drinking 8 glasses of water a day after surgery is important to flush the bladder and help healing.
Foods that help prevent constipation, such as fruits and vegetables, are important. A laxative may be needed if constipation occurs.
Kegel exercises can help reduce incontinence. Performing three to four sets of 30 contractions daily is recommended. In one study, improvement due to Kegel exercises was significant within a month after surgery.

Postoperative Complications. Complications after TURP can be high, depending on the skill of the surgeon and other factors, but their incidence has decreased considerably over the past decades because of advances in surgical technique and more widespread expertise.

Bleeding. Some blood and small clots appear in the urine after surgery, and if the bladder is flushed with water, the urine may turn red. Such bleeding is normal. Occasionally, the scab on the surgical wound loosens, causing a sudden appearance of blood in the urine that can be alarming. Usually this stops after a rest, but the patient should notify the doctor at once if he is concerned about abnormal bleeding or clotting or has unusual feelings of discomfort. Rarely, hemorrhage may occur, requiring a transfusion.
Infection. Urinary tract infections occur in 5 - 10% of TURP patients. The risk is particularly high if a catheter is required. Antibiotics may be given to prevent infections, although often a doctor will choose to monitor a patient and administer antibiotics only if an infection is evident.
Incontinence. Temporary stress incontinence (urine leakage after activities such as sneezing, coughing, or lifting) occurs in most surgical patients. Urge incontinence is the involuntary loss of urine following an uncontrollable urge to urinate. About 2.1% of TURP patients experience stress incontinence, and nearly 2% have urge incontinence. In general, however, there is no significant risk for incontinence. [See In-Depth Report #50: Urinary incontinence.]
Sexual Dysfunction. Some men report certain sexual differences after the procedure, particularly low volume of fluid at ejaculation. Studies, however, do not report any significant risk for impotence. For most men who report this complication, sexual function returns in short order. (In some men it may take up to a year for complete recovery.) If potency was diminished before the operation, the procedure will not restore it. [See In-Depth Report #15: Erectile dysfunction.]
Retrograde Ejaculation and Low Semen. Many TURP patients report a lower volume of semen after the procedure. Between 66 - 75% of these patients experience retrograde ejaculation, in which semen is forced backward into the bladder instead of forward out of the urethra during orgasm. During most invasive procedures, the muscle that blocks off the bladder may be cut in order to widen the outlet. In such cases, the semen flows back through the wider opening rather than out of the penis. This condition can impair fertility and is of particular concern in younger men. Neither retrograde ejaculation nor the operation itself typically affects orgasm, although it takes many men some time to emotionally adjust to these conditions.
Low PSA Levels. PSA levels may be lowered after TURP, which might cause a doctor to miss a diagnosis of prostate cancer during routine screening.

Repeat Operations. Symptomatic relief is usually maintained for at least 15 years after surgery, but BPH may return or patients may need a second operation for other reasons. Up to 10% of TURP patients require a repeat operation within 10 years. In some cases, scarring in the bladder severe enough to cause obstruction occurs within a year of the procedure and may require transurethral incision (TUIP). More often, the urethra is scarred and narrows, but usually this condition can be corrected by a simple stretching procedure performed in the doctor's office.

In transurethral incision of the prostate (TUIP), the surgeon makes only one or two incisions in the prostate, causing the bladder neck and the prostate to spring open and reduce pressure on the urethra.

Candidates. TUIP is generally used only for men with minimally enlarged prostates (30 grams or less) who have obstruction of the neck of the bladder. Some experts believe TUIP is not performed enough and could benefit many patients, particularly those with severe medical conditions who are not good candidates for more invasive surgeries and men who want to lessen their risk for sterility.

Postoperative Complications. TUIP is less invasive than TURP, has a lower rate of the same complications, particularly retrograde ejaculation, and usually does not require a hospital stay. More studies are still needed, however, to determine whether they are comparative in long-term effectiveness.

In open prostatectomy, the enlarged prostate is removed through an open incision in the abdomen using standard surgical techniques. This is major surgery and requires a hospital stay of several days. Open prostatectomy is used only for severe cases, about 2 - 3% of BPH patients, when the prostate is severely enlarged, the bladder is damaged, or other serious problems exist. Up to 14% of patients require a second operation because of scarring. In making a decision about prostatectomy, it is essential that the doctor explains the consequences of a diminished sexual capacity that occurs after this procedure. When the situation of the patient does not constitute an emergency, prostatectomy should be considered a last resort if the patient still has an active sex life. Other complications are similar to those of TURP.

Click the icon to see an illustrated series detailing prostatectomy surgery.

Procedures. Laser technology is used for removal of prostate tissue. Laser procedures can usually be done as an outpatient procedure, and there is little risk for bleeding. Different procedures are used to provide different degrees of thermal cell destruction that range from coagulation to complete vaporization:

Interstitial laser coagulation (ILC) involves insertion of a scope through the prostate. A fiberoptic tip is threaded through the scope to direct a diode laser emission to targeted areas of the prostate. The coagulated tissue is naturally absorbed back into the body. Approved in 1998, this procedure is being performed less frequently as urologists turn to newer laser technologies (HoLEP, PVP).
Holmium laser enucleation of the prostate (HoLEP) is a newer technique that can actually cut and vaporize the tissue. Vaporization is effective immediately and also may pose lower risks for prolonged urinary retention and reoperation rates than coagulation. The Holmium laser is showing very good results with low complication rates in small studies, and trials have reported benefits lasting more than four years. (HoLEP is actually proving to be better than TURP or even open prostatectomy for removing very large prostate glands.)
Photoselective vaporization of the prostate (PVP) uses a potassium-titanyl-phosphate (KTP) laser ("green-light" laser) to vaporize prostate tissue. The procedure is virtually bloodless and may be a better option for men taking anticoagulant medication. Results from several recent clinical trials report sustained improvement up to 1 year after the procedure. More studies are needed to confirm long-term efficacy.

Complications. The laser procedure carries a lower risk for incontinence than TURP or TUVP, another minimally invasive procedure. Studies have been mixed on whether laser surgery poses any risk for sexual dysfunction. In one study, TURP had a lower risk for sexual dysfunction, although the risk from either procedure was very low and it wasn't clear that lasers had even been responsible for this complication. After laser procedures, and especially after coagulation, the prostate often temporarily enlarged and caused obstruction and irritation. Sometimes these symptoms were severe. Most men require a temporary catheter to drain urine after laser procedures. Newer laser procedures may significantly reduce these adverse effects.

Transurethral Microwave Thermotherapy (TUMT). Transurethral microwave thermotherapy (TUMT) delivers heat using microwave pulses to destroy prostate tissue. Studies have found that between 60 - 80% of men respond favorably to the treatment and the benefits seem to last. A 2001 study reported that it remained effective for at least 18 months and was superior over the long-term to the alpha-blocker drug terazosin. Improvement is not as complete as with TURP, but TUMT has fewer complications.

Candidates. TUMT may be beneficial for men with larger prostates and moderate to severe bladder obstruction, including those who require indwelling catheters. A 2000 study, for example, concluded that is was a safe and effective therapy for treatment of urinary retention. In general, the procedure should not be performed on men who have pacemakers, defibrillators, or any metal implants. One possible exception, the Targis System, was approved for use for patients with hip or penile implants that are located at least 1.5 inches from the urethra. Men who have had previous radiation therapy to the pelvic area are at higher risk for injuries from this procedure.
Procedure. A microwave antenna is inserted through the urethra with ultrasound used to position it accurately. The antenna is enclosed in a cooling tube to protect the lining of the urethra. Computer-generated microwaves pulse through the antenna to heat and destroy prostate tissue. When the temperature becomes too high, the computer shuts down the heat and resumes treatment when a safe level has been reached. The procedure takes 30 minutes to 2 hours, and the patient can go home immediately afterward. About 30% of patients experience some pain during the procedure. The patient should report any pain that appears to be unusually severe, however, since this could indicate improper application.
Complications. Swelling in the urinary tract often occurs later, which prevents urination and requires the use of a temporary catheter for about 3 days until the swelling subsides. There have also been reports of serious injuries to the penis and urethra from overheating due to improper application. It is important to note that TUMT does not significantly affect sexuality or cause incontinence or retrograde ejaculation, which are risks with some other prostate procedures.

Transurethral Needle Ablation. Transurethral needle ablation (TUNA) is a simple, safe, and relatively inexpensive procedure using needles to deliver high-frequency radio waves that heat and destroy prostate tissue. The procedure usually requires only a local anesthetic. One study reported that improvement was maintained in most patients after 2 years, although older men (over 70) had slightly worse symptoms and quality-of-life scores. Although small clinical studies have reported that TUNA is as effective as TURP, some experts believe that in actual medical practice TURP is still more effective.

Some studies have reported urinary retention, blood in the urine, retrograde ejaculation, and painful urination after the procedure, although in general TUNA has few or none of TURP's severe side effects. TUNA poses a very low to no risk for incontinence and impotence, and may be a good option for younger men.

Transurethral Electrovaporization. Transurethral electrovaporization (TUVP) uses high voltage electrical current delivered through a resectoscope to combine vaporization of prostate tissue and coagulation that seals the blood and lymph vessels around the area. Deprived of blood, the excess tissue dies and is sloughed off over time. Patients who have TUVP may be able to have their catheter removed within hours after the procedure compared to normal removal time of 3 - 5 days after TURP. A 5-year study reported that it was as effective as TURP over the long-term and had a similar complication rate.

Ultrasound. High-intensity focus ultrasound (HIFU) is a heat procedure under investigation that uses ultrasound to destroy specific prostate tissue. The principles are similar to transurethral microwave thermotherapy, but ultrasound techniques may destroy excess tissue without damaging other parts of the urethra.

Water-Induced Thermotherapy. A device called Thermoflex, which circulates heated water through a catheter to destroy prostatic tissue, has been approved for treating BPH. Another technique uses a balloon filled with hot water to destroy tissue around the urethra. Water-induced thermotherapy (WIT) does not require anesthesia and can be completed during a single outpatient visit.

Prostatic stents used for BPH are flexible mesh tubes that are inserted into the urethra. They are made of special alloys that do not cause reactions in the body. Typically, the insertion procedure takes only 15 minutes and requires only regional anesthetic and mild sedation. It usually requires minimal recuperation and no overnight hospital stay. Unfortunately, long-term studies are reporting high rates of dissatisfaction. Between 8 - 37% of the stents need to be removed later because of poor placement or complications, including irritation when urinating, urinary tract infections, and treatment failure. At this point stents seem to be best suited for high-risk surgical patients and those with a limited life expectancy. Stents composed of new materials and properties may increase their role.

Resources

www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.urologyhealth.org -- American Urological Association

References

Bravi F, Bosetti C, Dal Maso L, Talamini R, Montella M, Negri E, et al. Food groups and risk of benign prostatic hyperplasia. Urology. 2006 Jan;67(1):73-9.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Rohrmann S, Giovannucci E, Willett WC, Platz EA. Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. Am. J. Clin. Nutr. 2007 Feb;85(2):523-9.

van der Meulen J, Brown CT, Yap T, Cromwell DA, Rixon L, Steed L, et al. Self management for men with lower urinary tract symptoms: randomised controlled trial. BMJ. 2007 Jan 6;334(7583):25. Epub 2006 Nov 21.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Urethritis

FitSugar — Wed, 08 Oct 2008 17:35:45 -0700

Overview

Signs and Symptoms
What Causes It?
What to Expect at Your Provider's Office
Treatment Options
Following Up
Special Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Urethritis is infection and inflammation of the lining of the urethra, the narrow tube that carries urine out of the body. In men, the urethra also carries semen. Urethritis is caused by bacteria and may impact the bladder, prostate, and reproductive organs. It can affect males and females of all ages. Females, however, are at higher risk.

Signs and Symptoms

There may be no symptoms of urethritis, particularly in women. When there are, symptoms include the following:

In men:

Burning during urination
Pus or whitish mucus discharge from the penis
Burning or itching around the penile opening

In women:

Painful urination
Unusual vaginal discharge

What Causes It?

Bacteria and other organisms entering the urethra
Bruising during sexual intercourse (in women)
Infection reaching the urethra from the prostate gland or through the penis opening (in men)
Bacterial infection after you have taken a course of antibiotics
Reiter's syndrome
Sexually transmitted diseases (STDs), such as chlamydia, syphilis, or HIV and AIDS

What to Expect at Your Provider's Office

Your health care provider will do a physical examination of your genitals, do laboratory tests on a urine sample, and take a specimen of mucus from inside the urethra and, in women, the vagina.

Treatment Options

Your health care provider may prescribe antibiotics to eliminate the organisms causing the infection.
All sex partners should be treated.
Sexual abstinence is recommended until treatment is completed, as disease can remain active even after symptoms have disappeared.

Prevention

Limit the number of sexual partners.
Always use condoms.
If you experience symptoms or suspect infections, seek treatment immediately and notify all sexual partners.

Drug Therapies

Depending on the cause of the infection, a physician may prescribe one of the following treatments:

Tetracycline, 500 mg four times a day, for 7 days.
Erythromycin, 500 mg four times a day, for 7 days (preferred in pregnancy).
Ceftriaxone, 250 mg IM once a day.
Ofloxacin, 400 mg once a day.
Ciprofloxacin, 500 mg once a day.
Doxycycline, 100 mg twice a day, for 10 days.
Metronidazole, 2 g orally once a day (not to be used during in pregnancy).
Clindamycin, 300 mg orally twice a day, for 7 days.
Acyclovir, 400 mg orally three times a day, for 10 days.
Famciclovir, 250 to 500 mg orally twice a day, for 10 days.
Valacyclovir, 1,000 mg orally twice a day, for 10 days.

Complementary and Alternative Therapies

Nutrition, herbs, and homeopathic remedies are useful in fighting infection, relieving pain, and strengthening the urinary system. Always tell your health care provider about the herbs and supplements you are using.

Nutrition and Supplements

Following these nutritional tips may help reduce symptoms:

Try to eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.
Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell peppers).
Avoid refined foods such as white breads, pastas, and sugar.
Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy) or beans for protein.
Use healthy cooking oils, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise at least 30 minutes daily, 5 days a week.

Nutritional deficiencies may be addressed with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, D, E, the B-vitamins and trace minerals, such as magnesium, calcium, zinc, and selenium.
Probiotic supplement (containing Lactobacillus acidophilus), 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 tablespoonful oil one to two times daily, to help decrease inflammation and improve immunity. Cold-water fish, such as salmon or halibut, are good sources.
L-theanine, 200 mg one to three times daily, for nervous system support.
Acetyl-L-carnitine, 500 mg daily, for antioxidant and muscle protective activity.
Grapefruit seed extract (Citrus paradisi), 100 mg capsule or 5 - 10 drops (in favorite beverage) three times daily, for antibacterial or antifungal activity and immunity.
Methylsulfonylmethane (MSM), 3,000 mg twice a day, to help decrease inflammation.

Natural hormone replacement therapy may be used for chronic urethritis. Check with your health care provider.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.

Cranberry (Vaccinium macrocarpon) standardized extract, 300 - 400 mg daily, for kidney health. You may also drink 8 - 16 ounces of unsweetened cranberry juice daily.
Green tea (Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant, anticancer and immune effects. Use caffeine free products. You may also prepare teas from the leaf of this herb.
Cat's claw (Uncaria tomentosa) standardized extract, 20 mg three times a day, for anticancer, immune, and antibacterial or antifungal activity.
Uva-ursi (Arctostaphylos uva-ursi ) standardized extract, 250 - 500 mg three times daily for no more than 4 days. You may also prepare teas from the leaf of this herb.
Bromelain (Ananus comosus) standardized, 40 mg three times daily, for pain and inflammation.

Homeopathy

Some of the most common remedies used for urethritis are listed below. Usually, the dose is three to five pellets of a 12X to 30C remedy every 1- 4 hours until your symptoms get better.

Staphysagria for urinary infections associated with sexual intercourse
Apis mellifica for stinging pains that are made worse by warmth
Cantharis for intolerable urging with "scalding" urine
Sarsaparilla for burning after urination

Acupuncture

Acupuncture may be helpful in enhancing your body's immune function, overall urogenital health, and for the acute pain of urethritis.

Following Up

If your urethritis was caused by a sexually transmitted disease, your sexual partners may need to be treated as well.

Special Considerations

STDs can cause permanent damage to reproductive organs and infertility in both sexes. They also can cause difficulties during pregnancy, premature delivery, low birth weight, and infections in newborns.

Supporting Research

Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA. 1994;271:751-754.

Bartram T. Encyclopedia of Herbal Medicine. Dorset, England: Grace Publishers; 1995:436-437.

Berkow R, Beers MH. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck and Company; 1992.

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, Mass: Integrative Medicine Communications; 1998:432.

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea--a review. J Am Coll Nutr. 2006;25(2):79-99.

Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr. 1999;69(6):1086-1107.

Cvetnic Z, Vladimir-Knezevic S. Antimicrobial activity of grapefruit seed and pulp ethanolic extract. Acta Pharm. 2004;54(3):243-50.

Doron S, Gorbach SL. Probiotics: their role in the treatment and prevention of disease. Expert Rev Anti Infect Ther. 2006;4(2):261-75.

Dryden GW Jr, Deaciuc I, Arteel G, McClain CJ. Clinical implications of oxidative stress and antioxidant therapy. Curr Gastroenterol Rep. 2005;7(4):308-16.

Gonclaves C, Dinis T, Batista MT. Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity. Phytochemistry. 2005;66(1):89-98.

Hoffman D. The New Holistic Herbal. New York, NY: Barnes & Noble Books; 1995:109-110.

JAMA Patient Page. How much vitamin C do you need? JAMA. 1999;281(15):1460.

Johnston CS. Recommendations for vitamin C intake. JAMA. 1999;282(22):2118-2119.

Hale LP, Greer PK, Trinh CT, James CL. Proteinase activity and stability of natural bromelain preparations. Int Immunopharmacol. 2005;5(4):783-93.

Heitzman ME, Neto CC, Winiarz E, Vaisberg AJ, Hammond GB. Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry. 2005;66(1):5-29.

Kruzel T. The Homeopathic Emergency Guide. Berkeley, Calif: North Atlantic Books; 1992:98-102.

LaValle JB, Krinsky DL, Hawkins EB, et al. Natural Therapeutics Pocket Guide. Hudson, OH:LexiComp; 2000: 452-454.

Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281(15):1415-1453.

Lieske JC, Goldfarb DS, De Simone C, Regnier C. Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int. 2005;68(3):1244-9.

Lichtenstein AH, Russell RM. Essential nutrients: food or supplements? Where should the emphasis be? JAMA. 2005;294(3):351-8.

Schindler G, Patzak U, Brinkhaus B. et al. Urinary excretion and metabolism of arbutin after oral administration of Arctostaphylos uvae ursi extract as film-coated tablets and aqueous solution in healthy humans. J Clin Pharmacol. 2002;42(:920-7.

Schmidt DR, Sobota AE. An examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates. Microbios. 1988;55:173-181.

Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. New York, NY: Springer; 1997.

Shealy CN. The Illustrated Encyclopedia of Healing Remedies. Boston, Mass: Element Books Limited; 1998.

Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002;21(6):495-505.

Tierney LM Jr, et al., ed. Current Medical Diagnosis & Treatment 1999. 38th ed. Stamford, Conn: Appleton & Lange; 1999.

Virtual Hospital: University of Iowa Family Practice Handbook. 3rd ed.

Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J. 2005;46(5):585-96.

Review Date:
8/12/2006
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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This Week With DearSugar

DearSugar — Sat, 30 Aug 2008 04:00:00 -0700

How well do you know condoms? Take this quiz and find out!
Have you ever been in a long-distance relationship?
Which movie is the absolute most likely to make your eyes red and your nose run?
Do you know your significant other's number one fantasy?
What do you think about sleeping in separate beds?
Is Peeved Penelope a Bridezilla, or is her friend a bad bridesmaid?
If you've ever snooped, have you read a friend's diary?
Do you think this Herpex commercial is funny or not?
Do you and your girlfriends have signals you use when you're out on the town?
See, men have problems too! Check out these three common penile problems.
How did you meet your hubby?
She saw her friend's fiancé kissing another woman. Should she tell? See what E. Jean had to say.
If you need a pick-me-up, check out my five easy suggestions.

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