ED pills and benign prostatic hyperplasia

No part of the human body is immune to the effects of aging. Many men face the double whammy of smaller erections and larger prostates as the clock ticks on. Although both erectile dysfunction (ED) and benign prostatic hyperplasia (BPH) become much more common as men age, they are very different problems with separate causes, unique symptoms, and unrelated consequences. Until now, treatments for the two conditions have also been different; in fact, medical and surgical therapies for BPH can sometimes even cause ED. But research suggests that the most popular and effective drugs for ED may substantially reduce the symptoms of BPH.

BPH: A primer

The prostate is a walnut-shaped gland at the base of the bladder. As part of the reproductive system, its job is to produce fluid for semen. But when things go wrong, the gland causes problems with urination, not sex. That's because the urethra, the tube that carries urine out from the bladder, runs right through the prostate.

In young men, the prostate is about an inch and a half long and weighs about two-thirds of an ounce. Starting in middle age, the gland begins to enlarge — and it doesn't take much enlargement to make urination difficult.

BPH causes three types of symptoms:

• Bladder storage symptoms include urinary urgency and frequency, excessive nighttime urination, and incontinence.

• Voiding symptoms include hesitancy, a weak urinary stream, straining to void, and incomplete bladder emptying.

• Post-voiding symptoms include dribbling after urination.

These lower urinary tract symptoms (LUTS in medical lingo) are common; they begin to mount as men enter their 60s, and they often increase as the prostate continues to enlarge over time. By the age of 80, about 25% of all men have BPH that is bothersome enough to require treatment, and countless others have mild symptoms they can "live with." Fortunately, though, serious complications are much less common; they include acute urinary retention, blood in the urine, bladder stones, urinary tract infections, and kidney dysfunction caused by the buildup of pressure in the urinary tract.

Because complications are relatively infrequent, many men can manage BPH themselves with simple lifestyle measures (see "Lifestyle management of BPH"). When more help is needed, doctors can prescribe medications or recommend surgery.

Two groups of medications are effective for BPH:

The alpha blockers relax smooth muscle cells in the prostate and bladder neck. The older drugs, terazosin (Hytrin, generic) and doxazosin (Cardura, generic) can cause dizziness by lowering the blood pressure too much in some men with BPH. The newer selective alpha blockers tamsulosin (Flomax, generic), alfuzosin (Uroxatral), and silodosin (Rapaflo) have much less effect on blood pressure. All these medications act within days to weeks, and about 70% of men with BPH improve. Side effects may include nasal stuffiness, headache, dry mouth, and decreased ejaculation (less likely with alfuzosin).

The hormone blockers, finasteride (Proscar, generic) and dutasteride (Avo dart), shrink the gland by blocking the conversion of testosterone to dihydrotestosterone, the male hormone that stimulates the prostate. These drugs work slowly, over six months or longer, and they are only helpful for men with rather large prostates. Side effects may include ED.

Combination therapy with an alpha blocker and a hormone blocker may reduce the risk of complications for men with large prostates and moderate to severe BPH.

Before modern medications were introduced, surgery was the only effective treatment for BPH. Although many men with BPH do well with drugs, others still need surgery. Several approaches are available:

• The transurethral resection of the prostate (TURP) has been the gold standard for BPH therapy. In recent years, though, its luster has tarnished — not because of problems with the operation itself (it's actually gotten better), but because of new medical and surgical rivals. Although results vary, TURP reduces BPH symptoms in 80% to 90% of patients. But there can be complications. Early problems include infection or bleeding. Late complications include dry ejaculation (50% to 75%), ED (5% to 10%), and incontinence (1% to 3%). And since the prostate can enlarge again, up to 20% of TURP patients require more treatment within 10 years.

• Newer, less invasive therapies. It sounds like alphabet soup: men who are considering new ways to treat BPH are now confronted by a bewildering array of initials, such as TUMT, TUNA, TUIP, HIFU, CLAP, TUBD, and believe it or not, many others. That's because urologists have devised many new therapies for BPH. Some use the energy from lasers, microwaves, ultrasound, or electricity to destroy unwanted prostate tissue, while others rely on tiny incisions in the gland. Because these therapies are new, they are not available in all hospitals. Long-term results are not known, but most appear more effective than medication, but less successful than TURP. Still, they may be worth considering since they generally have a lower risk of complications than TURP and allow a quicker return to normal activities.

Although BPH treatment has come a long way, it's far from perfect. Attempts to improve symptoms with herbs have been disappointing, but doctors continue to work on other approaches, ranging from improved laser surgery to Botox injections. And although ED pills would seem unlikely candidates to treat BPH, studies suggest they may help.

ED pills and sexual function

An erection is a hydraulic event that depends on a sixfold increase in penile blood flow. The crucial chemical for erections is nitric oxide, which transmits the impulses of arousal between nerves and also relaxes muscle cells in the penile arteries, causing them to widen and admit more blood.

Nitric oxide is essential for a normal erection, but it does not act alone. It signals the arterial cells to produce cyclic guanosine monophosphate (cGMP), the chemical that increases the flow of blood to the penis. But the tissues of the penis also produce phosphodiesterase-5 (PDE-5), an enzyme that breaks down cGMP.

In normal circumstances, the penis generates enough cGMP to produce a rigid erection and enough PDE-5 to end the erection when ejaculation is complete. But in many men with erectile dysfunction, this intricate system is out of balance, and sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) often sets things right. The ED pills all inhibit PDE-5, increasing the supply of cGMP; in about 70% of men with ED, the extra cGMP will allow firm and sustainable erections to develop in response to sexual stimulation.

In ED, pills are generally safe and well tolerated. In a few cases, they can produce painful prolonged erections (priapism). And they can occasionally lower blood pressure by widening arteries elsewhere in the body. That's why men who take any form of nitrate medication should never use ED pills, and it's why men with ED who take alpha blockers for BPH should choose a selective alpha blocker and must use ED pills with caution. Although these medications are generally safe for the heart, men with recent heart attacks or strokes, uncontrolled hypertension, or unstable angina should also abstain from ED pills.

The more common but less serious side effects of ED pills may also involve the arteries. Flushing, headaches, and nasal congestion head the list; other adverse reactions include backaches, muscle pain, indigestion, and rashes. These are all temporary symptoms, but sudden visual impairment or abrupt hearing loss, though rare, are serious indeed and can be permanent.

Beyond ED

Although the PDE-5 inhibitors have found huge success treating ED, they are beginning to show benefit for other conditions. Sildenafil and tadalafil have already been approved to treat pulmonary hypertension, an uncommon but very serious condition. And while ED pills have not yet been approved for other problems, research suggests they may help some patients with mountain sickness, Raynaud's phenomenon, heart failure, and possibly even stroke.

Because all these conditions involve blood vessels, scientists have had good reason to think ED pills may help. But BPH is different; it develops when stromal and epithelial cells in the prostate multiply and form microscopic nodules. Since BPH is a benign tumor, not a vascular problem, logic tells us that ED pills should be ineffective. But logic has its own limits, and research suggests that ED pills may indeed reduce symptoms of BPH.

Laboratory evidence

Most men think of BPH as a mechanical problem, with the enlarged prostate narrowing the urethra and obstructing the flow of urine, much as stepping on a garden hose blocks the flow of water. Indeed, mechanical obstruction is a major cause of lower urinary tract symptoms in BPH; that's why men with enlarged prostates respond to hormone-blocking medications that shrink the gland, while others need surgical procedures that eliminate excess tissue. Still, many men with BPH respond to alpha blockers that don't target mechanical obstruction; these medications work because they relax smooth muscle cells in the prostate and bladder neck, which facilitates the passage of urine.

Experiments with bladder and prostate tissue from men and mice show that nitric oxide and cGMP relax muscle cells in the bladder and prostate, much as these chemicals relax smooth muscle cells in the arteries of the penis and other organs. In addition, research shows that PDE-5 is present in the bladder and prostate, where it breaks down cGMP. That means drugs that target PDE-5 should be able to increase levels of cGMP in the bladder and prostate, thus helping muscle cells relax so urine can flow more easily. Since the ED pills inhibit PDE-5, they should be able to reduce symptoms of BPH.

Clinical evidence

The first ED pill, sildenafil, was approved in 1998. Almost instantaneously, it revolutionized the treatment of ED — but it took four years for researchers to report that the little blue pill also appeared to reduce symptoms of BPH, and even now, only a handful of studies have examined the possible role of ED pills in BPH.

Despite the lag, the studies are favorable. In randomized clinical trials, sildenafil, vardenafil, and tadalafil all appear to reduce lower urinary tract symptoms in men with BPH. The trials were brief, lasting 8 to 12 weeks, but several studies enrolled over 1,000 men. Men with both moderate and severe lower urinary tract symptoms improved. BPH symptoms improved to a similar degree in men with ED and in those with normal sexual function; obesity did not interfere with the benefits.

In these clinical trials, ED pills were administered daily. The medications were well tolerated, but since the studies ended within 12 weeks, long-term efficacy and safety cannot be assured. Still, tadalafil is approved for daily use by men with ED, and both sildenafil and tadalafil are approved for daily use by patients with pulmonary hypertension.

Time to double down?

The ED pills are not currently approved to treat BPH. Indeed, more research is needed to evaluate long-term efficacy and safety. It will also be important to conduct head-to-head comparisons between ED pills and medications already approved for BPH. Scientists should also evaluate combination therapy, particularly since doctors worry that ED pills may excessively lower blood pressure in men taking alpha blockers for BPH. And because the ED pills are much more expensive than BPH medications, cost is a factor in long-term therapy, especially since insurance does not cover ED pills for BPH.

Older men may be impatient for research results to flow in. But since many older gents have both ED and BPH, they may already be getting dual benefit from the ED pills. Our ancestors boasted of killing two birds with one stone, but modern men will be delighted to target two problems with one pill.