Benign Prostatic Hyperplasia Medication: Is It Really Effective?

What is Benign Prostatic Hyperplasia (BPH)?

Benign Prostatic Hyperplasia medication may not be necessary for every patient. Benign prostatic hyperplasia (BPH) is when the prostate and surrounding tissue expands. The prostate goes through two main growth periods as a man ages. The first is early in puberty, when the prostate doubles in size. The second begins around age 25 and continues during most of a man’s life. As you age, your prostate may get larger. BPH is when it gets large enough to cause problems.

While the prostate is usually the size of a walnut or golf ball in adult men, it can grow to be as large as an orange. As the gland enlarges, it can squeeze the urethra. The bladder wall becomes thicker. Over time the bladder may weaken and lose the ability to empty fully. Urine then remains in the bladder. These problems cause many of the lower urinary tract symptoms (LUTS) of BPH. If you are not able to pass urine at all (called retention) or if you have renal failure, immediate attention is required. But, other symptoms like weak urine stream or the need to push or strain can many times be monitored.

BPH is benign. This means it is not cancer, nor does it lead to cancer. Still, BPH and cancer can happen at the same time. BPH itself may not require any treatment, but if it begins to cause symptoms, treatment may help. It is also of great value to know that BPH is common. About half of all men between ages 51 and 60 have BPH. Up to 90% of men over age 80 have it.

Treatment Options for BPH

Currently, the main options to address BPH are:

• Watchful waiting
• Medication
• Surgery (prostatic urethral lift, transurethral resection of the prostate, photovaporization of the prostate, open prostatectomy)

If medications are ineffective in a man who is unable to withstand the rigors of surgery, urethral obstruction and incontinence may be managed by intermittent catheterization or an indwelling Foley catheter (which has an inflated balloon at the end to hold it in place in the bladder). The catheter can remain indefinitely (it is usually changed monthly).

Medication

Data is still being gathered on the benefits and possible adverse effects of long-term medical therapy. Currently, two types of drugs — 5-alpha-reductase inhibitors and alpha-adrenergic blockers — are used to treat BPH. Preliminary research suggests that these drugs improve symptoms in 30% to 60% of men, but it is not yet possible to predict who will respond to medical therapy or which drug will be better for an individual patient.

5-Alpha-Reductase Inhibitors

Finasteride (Proscar) blocks the conversion of testosterone to dihydrotestosterone, the major male sex hormone found in cells of the prostate. In some men, finasteride can relieve BPH symptoms, increase urinary flow rate and shrink the prostate, though it must be used indefinitely to prevent recurrence of symptoms, and it may take as long as six months to achieve maximum benefits.

In a study of its safety and effectiveness, two-thirds of the men taking finasteride experienced:

• At least a 20% decrease in prostate size (only about half achieved this level of reduction by the one-year mark)

• Improved urinary flow for about one-third of patients
• Some relief of symptoms for two-thirds of patients

A study published last year suggests that finasteride may be best suited for men with relatively large prostate glands. An analysis of six studies found that finasteride only improved BPH symptoms in men with an initial prostate volume of over 40 cubic centimeters — finasteride did not reduce symptoms in men with smaller glands. Since finasteride shrinks the prostate, men with smaller glands are probably less likely to respond to the drug because the urinary symptoms result from causes other than physical obstruction (for example, smooth muscle constriction). A recent study showed that over a four-year period of observation, finasteride treatment reduced the risk of developing urinary retention or requiring surgical treatment by 50%.

Finasteride use comes with some side effects. Impotence occurs in 3% to 4% of men taking the drug, and patients experience a 15% reduction in their sexual function scores regardless of their age and prostate size. Finasteride may also decrease the volume of ejaculate. Another adverse effect is gynecomastia (breast enlargement). A study from England found gynecomastia in 0.4% of patients taking the drug. About 80% of those who stop taking it have a partial or full remission of their breast enlargement. Because it is not clear that the drug causes gynecomastia or that it increases the risk of breast cancer, men taking finasteride are being carefully monitored until these issues are resolved. Men exposed to finasteride or dutasteride are also at risk of developing post-finasteride syndrome, which is characterized by a constellation of symptoms, including some that are sexual (reduced libido, ejaculatory dysfunction, erectile dysfunction), physical (gynecomastia, muscle weakness) and psychological (depression, anxiety, suicidal thoughts). These symptoms can persist long term despite discontinuation of finasteride.

Finasteride can lower PSA levels by about 50%, but it is not thought to limit the utility of PSA as a screening test for prostate cancer. The fall in PSA levels, and any adverse effects on sexual function, disappear when finasteride use is stopped.

To obtain the benefits of finasteride for BPH without compromising the detection of early prostate cancer, men should have a PSA test before starting finasteride treatment. Subsequent PSA values can then be compared to this baseline value. If a man is already on finasteride and no baseline PSA level was obtained, the results of a current PSA test should be multiplied by two to estimate the true PSA level. A fall in PSA of less than 50% after a year of finasteride treatment suggests either that the drug is not being taken or that prostate cancer might be present. Any increase in PSA levels while taking finasteride also raises the possibility of prostate cancer.

Alpha-Adrenergic Blockers

These drugs, originally used to treat high blood pressure, reduce the tension of smooth muscles in blood vessel walls and relax smooth muscle tissue in the prostate. As a result, daily use of an alpha-adrenergic drug may increase urinary flow and relieve symptoms of urinary frequency and nocturia. Some alpha-l-adrenergic drugs — for example, doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin) and tamsulosin (selective alpha 1-A receptor blocker — Flomax) — have been used for this purpose. One recent study found that 10 milligrams (mg) of terazosin daily produced a 30% reduction of BPH symptoms in about two-thirds of the men taking the drug. Lower daily doses of terazosin (2 and 5 mg) did not produce as much benefit as the 10 mg dose. The report’s authors recommended that physicians gradually increase the dose to 10 mg unless troublesome side effects occur. Possible side effects of alpha-adrenergic blockers are orthostatic hypotension (dizziness upon standing, due to a fall in blood pressure), fatigue and headaches. In this study, orthostatic hypotension was the most frequent side effect, and the authors noted that taking the daily dose in the evening can mitigate the problem. Another troubling side effect of alpha-blockers is the development of ejaculatory dysfunction (up to 16% of patients will experience this). In a study of over 2,000 BPH patients, a maximum of 10 mg of terazosin reduced average AUA Symptom Index scores from 20 to 12.4 over one year, compared to a drop from 20 to 16.3 in patients taking a placebo.

An advantage of alpha blockers, compared to finasteride, is that they work almost immediately. They also have the additional benefit of treating hypertension when it is present in BPH patients. However, whether terazosin is superior to finasteride may depend more on the prostate’s size. When the two drugs were compared in a study published in The New England Journal of Medicine, terazosin appeared to produce greater improvement of BPH symptoms and urinary flow rate than finasteride. But this difference may have been due to the larger number of men in the study with small prostates, who would be more likely to have BPH symptoms from smooth muscle constriction rather than from physical obstruction by excess glandular tissue. Doxazosin was evaluated in three clinical studies of 337 men with BPH. Patients took either a placebo or 4 mg to 12 mg of doxazosin per day. The active drug reduced urinary symptoms by 40% more than the placebo, and it increased urinary peak flow by an average of 2.2 ml/s (compared to 0.9 ml/s for the placebo patients).

Despite the previously held belief that doxazosin was only effective for mild or moderate BPH, patients with severe symptoms experienced the greatest improvement. Side effects including dizziness, fatigue, hypotension (low blood pressure), headache and insomnia led to withdrawal from the study by 10% of those on the active drug and 4% of those taking the placebo. Among men treated for hypertension, the doses of anti-hypertension drugs may need to be adjusted due to the blood-pressure-lowering effects of an alpha-adrenergic blocker.

Phosphodiesterase-5 Inhibitors

Phosphodiesterase-5 inhibitors, such as Cialis, are commonly used for erectile dysfunction, but when used daily, they also can relax the smooth muscle of the prostate and overactivity of the bladder muscle. Studies examining the impact of daily Cialis use compared to placebo demonstrated a reduction in International Prostate Symptom Score by four to five points, and Cialis was superior to placebo in reducing urinary frequency, urgency and urinary incontinence episodes. Studies examining Cialis’ impact on urine flow, however, have not shown meaningful change.