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A frank discussion of risks and benefits

Benign prostatic hyperplasia (BPH) is one of the most common disorders affecting men as they grow older. Yet there is much confusion about the best way to treat this disorder, in part because men taking medications for BPH are also likely to be taking other drugs for common medical problems, which may lead to adverse interactions and exacerbated side effects.

Harvard editors invited three Harvard experts to participate in a roundtable discussion to share their thoughts about the relative benefits and risks of current BPH medications. Participants included:

• Dr. Kevin Loughlin, professor of surgery (urology) at Harvard Medical School, who is senior surgeon and director of urologic research at Brigham and Women鈥檚 Hospital and staff urologist at Harvard University Health Services, a large university health program that serves the needs of Harvard students, faculty, employees, and their families.
• Dr. Abraham Morgentaler, associate clinical professor of surgery (urology) at Harvard Medical School and director of Men鈥檚 Health Boston. Dr. Morgentaler specializes in diseases of the prostate and has a particular interest in treating erectile dysfunction, low testosterone levels, and BPH. He has published widely on the issue of erectile dysfunction.
• Dr. Martin Sanda, associate professor of surgery (urology) at Harvard Medical School and director of the Prostate Care Center at Beth Israel Deaconess Hospital. Dr. Sanda has extensive experience in prostate cancer and BPH and has devoted much of his professional research to evaluating prostate-related treatment outcomes and developing new therapies.

Here, you鈥檒l learn what they think about who needs to be treated, what medications should be prescribed, and what side effects you need to be aware of. In short, after reading this article, you鈥檒l become a more discerning critic of the statements made during BPH drug advertisements that air during televised sporting events 鈥� and much more able to work with your doctor to make your own treatment decisions.

Who needs to be treated

What criteria do you use in determining whether to recommend treatment?

Morgentaler: One of the issues we鈥檙e always struggling with is who really needs to be treated at all. Some men may have relatively mild symptoms, in the spectrum of what we see, but they really are bothered by them and want to be treated, while other men may have really bad symptoms and are not interested in treatment at all. BPH treatment really comes down to patient preference and the impact of the condition on a person鈥檚 life.

Sanda: I agree. When we talk about treatment, we鈥檙e really talking about symptom management and symptom relief. The only time we鈥檇 urge someone without symptoms to begin medical treatment for BPH is if he began to suffer adverse consequences, such as infection due to retained urine or acute urinary retention, or if tests reveal scarring of the bladder, or any other sign that some type of irreversible damage is occurring in the bladder or kidneys. In such situations, we鈥檇 recommend treatment even if the patient is not particularly bothered by symptoms.

Loughlin: There鈥檚 actually a fairly narrow spectrum of absolute indications to treat BPH. Most people, probably more than 90%, are coming for relief of symptoms.

What medications should be prescribed

What criteria do you use in determining the type of BPH medication to recommend?

Loughlin: In general, alpha-1 blockers are best used in men with smaller prostates, 35 grams and smaller, and 5鈥揳lpha-reductase inhibitors are better for men with larger prostates, 55 grams and larger. This approach has been endorsed by several respected studies. Now, it鈥檚 not absolute. There鈥檚 judgment involved on the part of the urologist and the patient, but I think it鈥檚 a useful way to think of it, that with smaller glands you tend to use alpha-1 blockers, and with larger glands you tend to use 5鈥揳lpha-reductase inhibitors.

How is the size of the prostate best determined?

Loughlin: Your doctor can provide you with a rough estimate by doing a digital rectal exam. The other way to find out is to undergo a transrectal ultrasound 鈥� although that is usually ordered only if prostate cancer is suspected.

Of course, prostate size isn鈥檛 the only issue. Something else to consider is that alpha-1 blockers have a very rapid onset of action, days to weeks. 5鈥揳lpha-reductase inhibitors have a slow onset of action, three to six months. So in addition to size of the prostate gland, you need to understand from the patient how bothered he is by his symptoms and how long he can wait for relief.

Morgentaler: Definitely one factor that drives the choice of medication is how quickly a patient wants to see results. It鈥檚 very difficult to take a medication day after day, when it may not really have much impact for a few months. I think part of what drives the choice of alpha-1 blockers is that a patient will get relief fairly soon. On the other hand, if a patient wants to reduce the size of his prostate, then 5鈥揳lpha-reductase inhibitors are the better choice.

Is there a correlation between prostate gland size and symptoms?

Sanda: Well, that鈥檚 an interesting question, because the studies that have looked carefully at that issue have not found a great deal of correlation between prostate size and symptoms. But as Kevin mentioned, the size of the prostate helps determine whether a 5鈥揳lpha-reductase inhibitor has any role or not.

In my practice, I generally recommend alpha-1 blockers as the first line of treatment because of the immediacy of effect. And although the effectiveness of 5鈥揳lpha-reductase inhibitors is limited to men with large prostates, the converse is not true. In other words, alpha-1 blockers seem just as effective in men with larger prostates as in those with smaller prostates. So they have a broad spectrum of action, which is another reason why I tend to recommend alpha-1 blockers as a first-line therapy. I reserve 5鈥揳lpha-reductase inhibitors for those patients who, for one reason or another, do not get sufficient symptom relief from an alpha-1 blocker, and who have a large prostate, are not in an emergency situation, and have the patience to wait for several months before the medication takes effect.

Deciding which alpha-1 blockers are best

Do you prescribe the nonselective alpha-1 blockers anymore? Or just the selective alpha-1 blockers?

Sanda: The clear advantage of the selective alpha-1 blockers is that they are simpler to use and they take effect more quickly, because you don鈥檛 have to worry about titrating the dose. The first-generation nonselective drugs have to be titrated gradually. How long that takes depends on how much the drug affects that particular person鈥檚 blood pressure, and that鈥檚 quite variable. Some patients can reach a therapeutic dose of terazosin or doxazosin almost immediately without much effect on their blood pressure, but others need the dose increased much more slowly.

I also try to avoid the nonselective drugs because of their impact on blood pressure, but if I do prescribe them, I advise patients that if they experience lightheadedness and fatigue, or just feel washed out, that might indicate that their blood pressure is being affected too drastically by the medicine.

Morgentaler: I鈥檓 so glad that we have the newer selective alpha-1 blockers because I鈥檝e found that titrating of doses is very confusing for patients. There are certainly times when the nonselective alpha-1 blockers might be useful, but there鈥檚 no question in my mind that the new medications that generally have a single dose are simpler to prescribe, simpler to explain, and simpler for the patients to take.

Loughlin: I agree. A single-dose regimen is easier for the patient. If you ask someone who鈥檚 in his 80s and who鈥檚 already on six or seven other medications to titrate an alpha-1 blocker, you鈥檙e just asking for a drug error.

Morgentaler: I do prescribe the nonselective drugs for men if they鈥檝e been on one of the drugs for a long time and they鈥檝e been satisfied with it; then I鈥檒l just renew the prescription. A second issue is cost. Every now and again there are some formulary issues, where a health plan will only cover the nonselective alpha-1 blockers because they are less expensive.

Sanda: If cost is a concern, then I mention that both of the nonselective alpha-1 blockers are available in generic forms, which are cheaper than the prescription drugs.

Side effects of alpha-1 blockers

How do you advise patients who are taking antihypertensives?

Sanda: Certainly with the nonselective alpha-1 blockers there鈥檚 a great concern in terms of adjusting other antihypertensives. I think it鈥檚 much less of a concern with the selective alpha-1 blockers, such as Flomax.

Morgentaler: The one big issue that comes up with men who are on Flomax, although it can happen on any of the alpha-1 blockers, is the issue of ejaculatory dysfunction. This hasn鈥檛 shown up so much in the studies, or in the manufacturer鈥檚 materials, but we hear a lot about it from patients. Some men aren鈥檛 bothered at all, but others are really affected a lot.

Is ejaculatory dysfunction just a problem for the selective alpha-1 blockers, or do you also see it with the nonselective ones?

Morgentaler: This problem may have happened occasionally in men taking Cardura and Hytrin, but the complaints really increased when Flomax came out. I mean, it鈥檚 fairly routine now to have a patient talk to me about this problem. They say things like, 鈥淒oc, I have an orgasm and nothing comes out. There must be something terribly wrong with me.鈥� I find that if men are aware of this possibility ahead of time, so that they can anticipate it, they can deal with it. But when a man isn鈥檛 prepared, and when he鈥檚 still very interested in his sexuality, and his definition of potency includes ejaculatory potency, then it can become a problem.

Uroxatral is supposed to cause less ejaculatory disturbances. Have you found that to be the case?

Morgentaler: I personally have very little experience so far with Uroxatral. The data suggest that it鈥檚 not as much of a problem as it is with Flomax, but it鈥檚 still there.

Loughlin: I also tend to prescribe far more Flomax than Uroxatral, but that鈥檚 probably because Flomax has been around longer and my patients have been satisfied with it. But I think they鈥檙e probably about the same in terms of efficacy.

Are there any other key side effects that you see in people who take alpha-1 blockers for years?

Morgentaler: Every medication has risks, but over all, these medications are remarkably safe. The one thing that I do hear from patients, and it does show up in the literature as well, is that some people just don鈥檛 tolerate these medicines well. They feel lousy, weak, they don鈥檛 feel like themselves. But I think the number of men who experience that is fairly small.

And what do you do in those circumstances?

Morgentaler: Whenever I give a patient a medication, I try to alert him to the most common side effects. And I also tell him, you know, some guys just don鈥檛 tolerate certain kinds of medicine, and so you may feel weak or lousy. If it only lasts for a day or two, I advise them to try and get through it, but if they feel awful or the discomfort persists, I ask them to stop the medication and give me a call, and we can try something else.

Using BPH and erectile dysfunction drugs

The common wisdom is that it鈥檚 not safe to mix PDE-5 inhibitors with alpha-1 blockers. Is that really the case?

Morgentaler: I would say that, in my experience, the concern about combining alpha-1 blockers and PDE-5 inhibitors has lessened. Even the FDA has softened its cautionary language.

Loughlin: Most urologists today advise patients to take these medications at different times during the day rather than simultaneously. There鈥檚 not great compelling evidence that if you take them simultaneously anything terrible would happen, but it鈥檚 wise to be cautious.

So do you recommend taking the alpha-1 blocker in the morning and the erectile dysfunction drug in the evening?

Morgentaler: Frankly, I don鈥檛. I鈥檝e been prescribing these medicines since Viagra came out in 1998, and I鈥檝e never seen a single problem of hypotension from the combination. I think this is an issue that really has no substance to it.

Sanda: If a patient who is on an alpha-1 blocker is also using Viagra or another PDE-5 inhibitor, I mention that there have been some reports of interactions, but that I鈥檝e never encountered it in my practice and that I don鈥檛 know of any of my colleagues who have. I personally feel that it鈥檚 quite safe for people to use both types of drugs at once.

Other concerns about alpha-1 blockers

Do you believe there is the potential to aggravate BPH symptoms or urinary retention if your patients take over-the-counter medicines such as Sudafed during cold and flu season? And what are your thoughts about herbal and over-the-counter remedies?

Sanda: I鈥檝e certainly encountered many men who have gone into urinary retention while taking over-the-counter cold remedies. I think it鈥檚 important for any man with BPH, whether or not he鈥檚 being treated, to be aware that medications for nasal congestion can exacerbate urinary problems and could potentially lead to acute urinary retention. To avoid problems, I advise patients to pay attention to any changes in urination while they are taking Sudafed or similar agents.

Loughlin: Another thing men with BPH may want to be aware of is that there are a lot of people out there who still take saw palmetto and swear by it, and I think it鈥檚 important to say that the best study done on saw palmetto, which was published in the New England Journal of Medicine, found that it鈥檚 no better than placebo [see 鈥淗ow effective is saw palmetto?鈥� below].

Most herbal therapies do appear to be safe. But they are not FDA-regulated. A lot of patients don鈥檛 consider herbal remedies to be drugs, and technically they鈥檙e not, but sometimes they interact with medications. If you are taking an herbal remedy, it鈥檚 important that you mention it to your doctor.

Sanda: I probably take an even stronger stance. On the one hand, I certainly tell patients that if they鈥檙e on herbal remedies, I can accept that and that鈥檚 okay, but I do like to mention the PC-SPES story, and the reality that there are herbal medications that have been used for prostate conditions in the past, but when they were evaluated more rigorously were found to actually be dangerous to patients. [Note: PC-SPES was pulled from the market because of concerns about contamination.] The real issue is that the danger wasn鈥檛 evident for many years while those formulations were being used by many people. I think men need to be aware that there is the potential for hidden dangers in those herbal remedies and probably a greater potential among those than there is among the FDA-approved drugs.

5鈥揳lpha-reductase inhibitors

Do you recommend one 5鈥揳lpha-reductase inhibitor more than the other?

Loughlin: At this point, there鈥檚 no evidence that one or the other is superior. There are studies ongoing to see whether that may be true, but I think from a patient鈥檚 point of view, there鈥檚 no evidence that Proscar is better than Avodart or vice versa.

What kind of side effects do you see with the 5鈥揳lpha-reductase inhibitors?

Loughlin: Both can cause gynecomastia [enlargement of the breasts in men]. It doesn鈥檛 happen in a large percentage of patients, but some men are extremely bothered by it, and I think it鈥檚 something that鈥檚 important to tell a patient before he starts taking one of these drugs.

Is there any way to identify men who are more likely to develop this problem?

Loughlin: Unfortunately, no. And when you stop taking a 5鈥揳lpha-reductase inhibitor, in my experience, the gynecomastia does not always go away. So it happens in a small percentage of men, but when it does happen, it can be bothersome. I can remember at least one man whom we actually had to refer to a plastic surgeon to talk about having breast reduction surgery.

Sanda: It鈥檚 not one of the more common problems, but it can happen. What I鈥檝e encountered more often are complaints about reduced ejaculate volume, and physical changes such diminishment in the size of the flaccid penis.

Morgentaler: I do a lot of research on testosterone, and gynecomastia can be a sign of low testosterone. So it may be that the 5鈥揳lpha-reductase inhibitors cause gynecomastia because of their effect on testosterone.

But I actually can鈥檛 remember ever seeing anybody on Proscar or Avodart in my practice who developed gynecomastia, although clearly it happens. I just don鈥檛 remember seeing it. It must be relatively uncommon. This probably develops in men who are somehow predisposed to it. It can be treated by plastic surgery or in some cases, radiation.

5鈥揳lpha-reductase inhibitors, prostate cancer, and PSA

What did you think of the Prostate Cancer Prevention Trial (PCPT) and what it means for patients taking one of the 5鈥揳lpha-reductase inhibitors?

Loughlin: The study is interesting, certainly, but we don鈥檛 have the final answer yet about whether Proscar really does decrease the risk of cancer. I think the honest assessment at this point is that the study has raised the possibility of this effect, and it鈥檚 being actively investigated, but we don鈥檛 have a resolution of that question yet. So, that鈥檚 something that readers need to be aware of and they need to talk about with their urologist.

Morgentaler: You know, it鈥檚 a fascinating study. On the one hand, taking Proscar caused a remarkable reduction in prostate cancer, a 25% reduction. I mean, we would hope for treatments for other kinds of conditions that would have the success rate as good as that. And yet at the same time it looks as if taking Proscar increased the cancers that probably are the most worrisome in terms of mortality and morbidity, so it鈥檚 really hard to know what to make of that.

I personally don鈥檛 use finasteride or 5鈥揳lpha-reductase inhibitors for prevention. I don鈥檛 know too many doctors who do.

Sanda: It clearly hasn鈥檛 caught on, precisely because of the concerns about the downside 鈥� of whether increasing the risk of developing an aggressive cancer outweighs the possible benefit of reducing overall risk of cancer.

Loughlin: Although if we鈥檙e talking about monitoring risk, anyone taking a 5鈥揳lpha-reductase inhibitor should be aware that it will change their PSA level. Generally speaking, after a man has been on a 5鈥揳lpha-reductase inhibitor for several months, his PSA should decrease by half. And then you can interpret that PSA as you would any other PSA by doubling it. Alpha-1 blockers don鈥檛 affect PSA levels.

Morgentaler: And even though the common wisdom is that you double the PSA once a man is on a 5鈥揳lpha-reductase inhibitor, it鈥檚 important to point out that that鈥檚 actually an average, and that not everybody is going to have his PSA reduced by half while on one of these medications. There are always differences with individuals, and when somebody鈥檚 had a PSA level increase from 3 to 3.5, and then up to 4, and then we鈥檝e put them on a 5鈥揳lpha-reductase inhibitor, some of those guys don鈥檛 see their PSA levels go from 4 to 2. Some of them may go from 4 to 3, and some may go from 4 to 1. So it鈥檚 important to establish a baseline PSA before you begin taking a 5鈥揳lpha-reductase inhibitor, and then get tested again after taking the medication for six months or so.

Acute urinary retention

When you counsel patients, what do you tell them about avoiding problems with acute urinary retention? Is there any way for a man taking a BPH medication to avoid developing this problem while taking a plane trip or at a sporting event 鈥� where he may not have easy access to a toilet and need to hold in his urine?

Loughlin: Well, unfortunately, I don鈥檛 think there鈥檚 a clearly identifiable prodrome that says Mr. Jones is likely to go into retention during a plane trip while Mr. Smith isn鈥檛. We sometimes see this problem develop during a non-urologic surgical procedure, where they go into retention as a consequence of anesthesia.

Sanda: Usually there are no warning signs of who is going to go into retention. Of course, if the symptoms are increasing in severity, then it may well be a sign that the bladder is being damaged because of the obstruction. And you may be able to avoid problems by increasing the dose of your medication or changing your medication. So if the symptoms get worse, definitely contact your doctor. Make an adjustment.

Morgentaler: As a rule, I do not speak to my patients about urinary retention if I鈥檓 treating them for BPH, unless there is something about their situation that sort of raises a red flag. If a man has an enormous prostate, if I have objective data like urine flows that are very weak or post-void residuals that are substantial, or I think that maybe a small additional insult may tip him over into retention, then I might discuss some options with him. But I think it鈥檚 important to recognize that urinary retention can happen even in the absence of a prostate: It happens to women. And it sometimes happens after people receive certain anesthetics, if they鈥檙e on narcotics, if they鈥檙e older, or if they become constipated.

Combination medical therapy

When do you recommend combination therapy for someone with BPH?

Loughlin: The Medical Therapy of Prostatic Symptoms (MTOPS) study showed that combination therapy clearly has a role. Obviously, these two classes of drugs have different mechanisms of action, so if you use both drugs simultaneously, chances are you鈥檒l have a higher response rate. The downside is that the cost is increased when you鈥檙e using two drugs, and each type of drug has its own side effect profile, so you may increase the likelihood of experiencing side effects.

We usually don鈥檛 start off with combination therapy. But if one of my patients has a large prostate gland and yet is eager to see results soon, then sometimes I simultaneously prescribe both an alpha-1 blocker and a 5鈥揳lpha-reductase inhibitor, with the plan to drop the alpha-1 blocker in six months or so, once the other medication has begun to show results. That鈥檚 a reasonable strategy for some men.

Originally published Jan. 1, 2007; last reviewed April 26, 2011.