Health and Prostate

As mentioned earlier, there are two main groups of drugs commonly used to treat BPH: alpha-blockers and 5-alpha-reductase inhibitors. (See Table 1 and Table 2 for the commonly used dosages and for a brief description of how they differ.)

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Your doctor is most likely to prescribe an alpha-blocker as the first line of treatment if you need a drug to treat your benign prostatic hypertrophy. That’s primarily because those drugs take effect quickly and — for most men-help relieve urination problems and other symptoms in a matter of days or weeks. About 60 percent of men treated with alpha-blockers experience an improvement in their symptoms.

Alpha-blockers are also less expensive than the 5-alpha-reductase inhibitors. The three oldest alpha-blockers — immediate-release doxazosin (Cardura), prazosin (Minipress), and terazosin (Hytrin) — are available in lower-cost generic forms, and typically cost less than $35 for a month’s supply. (See Table 3) Prazosin is generally not used to treat urinary problems due to prostate enlargement because it is not approved by the Food and Drug Administration (FDA) for the condition. It is also less convenient because it must be taken twice per day, whereas the other alpha-blockers are taken once daily. But prazosin, which is FDA-approved to treat high blood pressure, is sometimes an option if you have both urinary problems from an enlarged prostate and high blood pressure.

Three newer alpha-blockers — alfuzosin (Uroxatrol), tamsulosin (Flomax), and doxazosin-sustained release (Cardura XL) — are available in extended-release or continuous-release forms designed to keep them working in your body all day long. That may have advantages for some patients, but our analysis found no compelling evidence to indicate that those three medicines were any better than the older, immediate-release alpha-blockers in terms of reducing symptoms or improving quality of life.

Moreover, those longer-acting drugs are significantly more expensive than the immediate-release formulations. Flomax, which is one of the most expensive alpha-blockers, has a unique issue when it comes to cost. It is only available in one dosage strength, so if you need to increase your dose to get relief from your symptoms, you will need to take two pills, which doubles the cost. The other alpha-blockers are available in varying strengths for about the same price, so even if you need a stronger dose, it will cost you about the same.

Another point to keep in mind when it comes to cost is that you can save money by buying higher-dose tablets and splitting them in half with your doctor’s or pharmacist’s approval. (You can only split pills that are immediate release tablets, such as doxazosin and terazosin. Splitting should not be done with extended-release or sustained-release tablets). For example, if you are taking 4 mg of doxazosin per day, you could buy the 8 mg pill for about the same price and split it. You should use a pill-splitter to make certain that the two halves are the same size and provide you with the correct dose. These devices cost about $5 to $10 and are widely available.

Studies indicate that all alpha-blockers yield about the same clinical results in controlling symptoms and improving quality of life. Unfortunately, only a few studies directly compare the different alpha-blockers head to head. But to date they have found no advantage for one alpha-blocker over another.

Also, little research has been done on whether race or age makes a difference in how men respond to the BPH drugs. Some major studies have included very elderly men and black men, but so far there is no definitive evidence that the effectiveness or side effects of treatment differ between black and white men or older men.

Silodosin (Rapaflo) is the newest alpha-blocker. The FDA approved this medicine in late 2008. In two studies involving a total of 923 men, those receiving Rapaflo showed an improvement in their symptoms and urinary-flow rate compared with those who took a placebo pill over 12 weeks. But since the drug does not have the long track record of use of some of the other alpha-blockers, its safety profile is not yet firmly established. In addition, it’s more expensive. For those reasons, we’d advise it not be used as initial treatment at this time.

How the drugs work

The 5-alpha-reductase inhibitors work in a much different way than the alpha-blockers. While the alpha-blockers relax muscles in the bladder, the 5-alpha reductase inhibitors actually shrink the prostate by blocking the abnormal buildup of the hormone dihyroxytestosterone — a testosterone derivative — that can cause it to swell and become enlarged. The 5-alpha-reductase inhibitors help relieve symptoms but can take as long as 6 to 12 months before they work. And studies show they are much more likely to be effective in men with more severely enlarged prostates.

The two 5-alpha-reductase inhibitors are finasteride (Proscar and generic) and dutasteride (Avodart). Finasteride is also sold under the name Propecia as a treatment for male pattern baldness, but this is a lower-dose tablet that is not approved by the FDA for treating benign prostatic hypertrophy. Generic finasteride costs less than Avodart but it’s still more expensive than the generic alpha-blockers.

Studies don’t indicate any difference in the effectiveness or safety of finasteride and dutasteride, and at the current time neither is known to have any advantages over the other.

The 5-alpha-reductase inhibitors are sometimes prescribed initially, before an alpha-blocker, but this is quite rare. They are more commonly prescribed if an alpha-blocker has failed to relieve your symptoms or as a second drug to augment an alpha-blocker if you are not getting enough relief.

One potential benefit of the 5-alpha-reductase inhibitors is that they might reduce the risk of developing prostate cancer. However, you should be aware that there is debate among experts about whether those drugs actually increase the risk of cancers that are more difficult to treat. As this report goes to print, the controversy has not been fully resolved to our satisfaction. This is an issue you need to discuss with your doctor to make the best-informed decision you can.

Side effects

You and your doctor’s choice of a BPH drug may be based more on its side effect profile than effectiveness.

The most common side effects of alpha-blockers are reduced semen during ejaculation, headache, upset stomach, and stuffy or runny nose. The drugs can also cause low blood pressure, dizziness, and fainting, especially when you first start taking them, so it’s important to take precautions to prevent any injuries that could result from this. That includes taking the drug before you go to sleep, so you’re already laying down if problems do occur, and not driving or operating machinery when you first start taking it.

With the older drugs — doxazosin, terazosin, and prazosin — your doctor should start you on a low dose and build up to a higher dose over a period of a few weeks to give your body time to adjust to the medicine. That process is not necessary with the newer alpha-blockers (Flomax, Rapaflo, and Uroxatral).

Low blood pressure caused by the alpha-blocker medicines can fall to dangerous levels if you’re also taking a high blood pressure drug or erectile dysfunction medicines such as sildenafil (Viagra), varde-nafil (Levitra), and tadalafil (Cialis). So don’t take an alpha-blocker with those other drugs without first discussing it with your doctor.

Men with prostate enlargement who are planning to have cataract surgery should be aware that all alpha-blockers can cause a complication called intraoperative floppy iris syndrome, or MS. This condition causes the iris of the eye to become limp due to increases in fluid levels in the eye. This is a concern because it can raise the risk of a painful and extended recovery period from cataract surgery and a reduction in visual acuity or sharpness after the surgery. You should alert your eye surgeon that you are taking alpha-blockers if you plan on having this surgery.

In very rare cases, the alpha-blockers can cause painful erections that last for hours. If not treated, this can lead to a permanent inability to achieve erection, so you should seek immediate medical attention if you develop this condition.

The side effects of the 5-alpha-reductase inhibitors may include a reduced sex drive and difficulty achieving and maintaining an erection. While these can be bothersome for many men, in clinical studies only around 2 percent of those who developed any sexual difficulties found them to be severe enough to stop taking the medicines.

The 5-alpha-reductase inhibitors can also cause birth defects in developing fetuses. So men should avoid using 5-alpha-reductase inhibitors when planning a pregnancy with their female partners, and the medicines should not be handled by women who are pregnant or planning to become pregnant.

Finally, the 5-alpha-reductase inhibitors can reduce levels of prostate specific antigen, or PSA, that is used to screen for prostate cancer. Patients who are appropriate candidates for these drugs tend to have higher PSA levels, but if the medicines lower their prostate-specific antigen levels it could make it more difficult to detect prostate cancer. There are strategies that attempt to account for this issue when reading the results of prostate-specific antigen tests, so make sure your doctor is aware that you are taking one of these drugs if your PSA level is being tested.

Our Best Buy Pick

For initial treatment of BPH, we have ruled out three of the alpha-blockers: silodosin (Rapaflo) because it is too new; prazosin because it is not FDA-approved for treating BPH and its twice-per-day dosing makes it more inconvenient than the other alpha-blockers; and tamsulosin (Flomax) because of its higher cost while not being any more effective or safer than the other medicines. We would also advise against alfuzosin (Uroxatral) and Cardura XL, since they are more expensive and their extended-release formulation has not been proven to be safer or more effective than the older alpha-blockers.

That leaves two generic alpha-blocker drugs for consideration: doxazosin and terazosin. Given that there is no evidence that either of those is more effective or safer than the other, we have chosen generic doxazosin as our Best Buy for initial treatment of benign prostatic hypertrophy due largely to its lower cost.

This medicine has been on the market for several decades, so its safety and effectiveness profile is well established. And a month’s supply costs less than $10. If doxazosin works for you, the savings would be significant over taking one of the costly brand-name alpha-blockers.

If doxazosin does not bring enough relief, you should try terazosin next. Or you could also try adding finasteride.

Combination therapy?

For men who do not get enough relief from an alpha-blocker, adding a 5-alpha-reductase inhibitor is an option. Again, your doctor is unlikely to recommend this unless your prostate is significantly enlarged and your symptoms are bothersome.

But be warned: This may not bring immediate relief. Studies indicate that combination treatment with an alpha-blocker and a 5-alpha-reductase inhibitor doesn’t generally provide additional benefit over an alpha-blocker alone in the first 12 months of treatment. Over the long-term, however, combination therapy appears to help prevent the symptoms from becoming worse. And it can also prevent serious complications, such as not being able to urinate at all (called acute urinary retention), which often leads to prostate surgery.

One study, for example, found that after four years of treatment with both the alpha-blocker doxazosin and the 5-alpha-reductase inhibitor finasteride, symptoms worsened in only 5.3% of the men compared with about 10% of those who received either drug alone. Men with the greatest prostate enlargement got the most benefit from the combination therapy. Another study involving the combination treatment of the alpha-blocker tamsulosin and the 5-alpha-reductase inhibitor dutasteride (Avodart) in men with very large prostates found that both drugs together provided greater improvement in symptoms after one and two years of treatment than either drug alone.

However, due to the increased risk of side effects with combination therapy, this treatment strategy is typically limited to men with bothersome symptoms and very enlarged prostates.

If you and your doctor decide that a combination strategy is appropriate for your condition, we recommend that you try doxazosin plus finasteride. This is the only combination treatment that has been proven to have a long-term benefit of delaying progression of symptoms over four years. In addition, as previously noted, both drugs are available as less-expensive generics.

1. ‘Generic’ indicates that it’s the generic version of the drug.
2. As typically prescribed.
3. Prices reflect nationwide retail average for February 2009, rounded to the nearest dollar if you were to pay the cash price. Information derived from data provided by Wolters Kluwer Health, Pharmaceutical Audit Suite®. Wolters Kluwer Health is not involved in our analysis or recommendations.
4. Silodosin (Rapaflo) had not yet gone on sale when this report was developed, so price data was not available. 06/2010 – $365
5. Weighted averages were used to calculate the generic version of terazosin for 1 mg, 2 mg, 5 mg, and 10 mg capsules.

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