Testosterone and the prostate

Joel M. Kaufman, MD interviewed by Hugo Verhoeven, MD

Hugo Verhoeven, MD: Good afternoon ladies and gentlemen, my name is Hugo Verhoeven from the Centre for Reproductive Medicine and Endocrinology in Dusseldorf, Germany. I’m reporting from the 4th World Congress on the Aging Male here in Prague.

I am sitting with Dr. Kaufman from the University of Colorado. He is an Associate Clinical Professor at the University of Colorado, and it’s a great pleasure for me, being together with him here. Dr. Kaufman, I heard this afternoon your presentation on testosterone treatment in patients with prostate cancer or with BPH. For our listeners, maybe first, what exactly is BPH? And why should there be a relationship between androgens, BPH and prostatic cancer?

Joel M. Kaufman, MD: Well BPH means benign prostatic hypertrophy or an enlarged prostate. It’s a common condition in men as they get older, and it cases urinary difficulties; slow urinary stream, frequent urination. We know that the prostate is stimulated by testosterone, and the concern is that if you treat men who have prostate problems with testosterone that you might worsen their prostate problems.

Hugo Verhoeven, MD: Why is testosterone inducing BPH? Or inducing prostatic cancer, is there any aetiology known?

Joel M. Kaufman, MD: There is no aetiology that testosterone induces prostate cancer, but what we know is that the prostate cells are sensitive to testosterone. Men who do not have testosterone tend have very small prostates. The prostate requires testosterone to grow. After the age of 50, that’s when we tend to see problems with low testosterone, but it’s also the age group where men start to have enlarged prostates and may develop prostate cancer.

Hugo Verhoeven, MD: Can we say the higher the free testosterone level in the blood, the higher the risk of BPH, and maybe also the higher the risk of prostatic cancer, or is there no relation between those two?

Joel M. Kaufman, MD: There is no correlation at all. There have been a lot of studies; I referred to them today that show no correlation between testosterone levels and any prostate parameter.

Hugo Verhoeven, MD: So how can we then screen our patients for the risk that they are going to have BPH, or later on, prostatic cancer? Free testosterone will not be a good parameter for that.

Joel M. Kaufman, MD: No, the free testosterone is the way that you’re diagnosing hypogonadism. But before you start somebody, particularly men over the age of 50, on testosterone treatment you need to be sure they don’t have a prostate problem. You can determine that by symptoms. If a man is having a great deal of difficulty urinating, you probably would not want to stimulate his prostate with testosterone. In terms of prostate cancer, the rectal examination is very helpful and the PSA is probably the most helpful measure to make sure somebody doesn’t have prostate cancer.

Hugo Verhoeven, MD: Am I understanding you correctly that even a patient with very low free testosterone, a hypogonadal man, could be at high risk for BPH?

Joel M. Kaufman, MD: No, a man who is severely hypogonadal probably is not going to have much of a prostate problem. But men who are mildly hypogonadal could have prostate cancer or BPH. When you give them testosterone replacement, you may stimulate the prostate cancer, or the BPH.

Hugo Verhoeven, MD: Myself, I’m a gynaecologist, a gynaecological-endocrinologist, and we use, of course, hormone replacement therapy in gynaecology for many, many, many years. There is now, more and more the tendency to treat, hypogonadal men anyway, but also eugonadal men with testosterone. The big fear is of course, are we harming the prostate, yes or no? Let’s start with men who are hypogonadal. If we treat them with testosterone, do you think there is a risk for them to develop BPH and prostatic cancer?

Joel M. Kaufman, MD: There is, when you bring the testosterone level into the normal range, now the prostate is being stimulated in a normal way. When they were hypogonadal, there was very little stimulation of the prostate. So, if somebody is harbouring a few prostate cancer cells, they may get stimulated by raising the testosterone up to a normal range, and you may develop a clinically significant cancer.

In terms of BPH, the same thing can happen. A man can get growth of his prostate when he receives testosterone therapy, and that can cause difficulty with urination.

Hugo Verhoeven, MD: In the part of the world where I am working there is a tendency to treat men with a normal testosterone level, who have clinical symptoms of aging, and they ask for treatment with testosterone or with growth hormone. Of course, the immediate question is always, “the only thing I don’t want, I don’t want to have prostatic cancer”.

So, now talking about men with normal levels of testosterone, if we are going to supraphysiological dosages, what is then the risk of BPH?

Joel M. Kaufman, MD: I don’t treat men who have normal levels of testosterone. I think that’s the wrong thing to do. I think it’s dangerous to do that, particularly regarding the prostate. There’s no evidence, that I’m aware of, that raising testosterone levels above the normal range is beneficial to a man. So I would disagree with doing that.

Hugo Verhoeven, MD: Body builders?

Joel M. Kaufman, MD: Body builders, well, look at what happens to them. They die of liver problems and so forth. I see no reason to take somebody above the normal range.

Hugo Verhoeven, MD: Now let’s go to patients with BPH and prostatic cancer. Even patients with BPH will come to see us and they will say, “We want testosterone treatment. We are hypogonadal”. What is your answer to this problem?

Joel M. Kaufman, MD: My feeling is that if they have symptoms of hypogonadism, and a low testosterone level by whatever measure you use, that’s the patient that should be treated. Unfortunately we don’t know that somebody in the low-normal range might not benefit, so when I say you shouldn’t treat somebody, if somebody is in the normal-normal range, I would be reluctant to treat that individual. But an individual in the low-normal range, who has symptoms suggestive of hypogonadism, I think it’s perfectly reasonable to treat.

But you have to recognise that many of the symptoms of hypogonadism are not specific; low energy levels, fatigue, low sex drive, those are not necessarily related to testosterone. When I start somebody on testosterone therapy for these non-specific symptoms, I see them back after a month or so, and determine whether or not I’ve helped them. If they tell me that their symptoms are not better, then I don’t continue the treatment. If they say the symptoms are better, then I do continue the treatment.

Hugo Verhoeven, MD: Let’s switch now to the next, I think, very important topic; what about patients with prostatic cancer? I think practically everybody will say “I will never treat somebody who has had prostatic cancer with testosterone”. I heard today, during your lecture, that your opinion on that has changed, please tell us about that.

Joel M. Kaufman, MD: Nowadays we are diagnosing prostate cancer at a very early stage. We have excellent screening methods, and we identify prostate cancer at a time that it’s usually curable. So, if you’ve done a curable treatment, particularly surgery, and subsequently the patient is found to be hypogonadal, my own feeling is that it’s okay to treat them with testosterone, provided that you are pretty confident that they are cured. If they are not cured, I think it’s risky to give them testosterone.

Hugo Verhoeven, MD: How can you be so sure that he’s really cured? What are your criteria?

Joel M. Kaufman, MD: The PSA is an excellent measure. When the PSA is zero, or nearly zero, that indicates that there is no prostate cancer in that man’s body. The PSA has to be zero or undetectable before I would start a man on testosterone.

If the PSA is detectable, that man still has prostate cancer and I would not treat him.

Hugo Verhoeven, MD: But as soon as the PSA goes to zero, how long will you follow up the patients? It could be that after a certain amount of time the PSA is going up again.

Joel M. Kaufman, MD: Yes we have other ways of looking at it. For example, if prior to treatment, the PSA is in the low range. In our series, all the PSAs were in the four to six range before they had their surgeries. If the pathology report indicates that the cancer was confined to the prostate, indicating that you probably cured them with surgery, and if the histologic rating, the Gleeson score, is in the moderate range, then there’s a better than 95% chance that that patient is going to be cured.

As you follow that man three months, six months after surgery, if the PSA is indeed zero, along with these other parameters and guides, you can pretty well tell that you’ve cured that patient. Now you won’t have 100% certainty, but it’s say, a 95% certainty.

If that man is severely hypogonadal and needs treatment, and is willing to accept that there is small risk associated with the treatment, then I think it is ok to go ahead.

Hugo Verhoeven, MD: I only ask you that because in gynaecology and endocrinology the five year follow up seems to be very important.

Joel M. Kaufman, MD: What’s different about prostate cancer is that we have this unique marker, the PSA. If the PSA is zero at three months or six months, there’s an excellent chance that it’s always going to be zero.

We have very few cancers where we have that accurate a marker. That’s why for most cancers we say five years before they are cured, but you can tell a lot earlier than that that a man is probably cured of his prostate cancer if the PSA is undetectable.

Hugo Verhoeven, MD: We have different possibilities of administration of androgens nowadays. Is there any difference or any preference for you how you would treat a patient with BPH or with prostatic cancer? Are you choosing different ways of therapy?

Joel M. Kaufman, MD: In the United States we really only have two forms of therapy. The topical and we have injections. I discourage men from using the injections. Not only is there pain associated with it, but you get very high supraphysiologic levels in the first week, and then after the second week the levels are back in the sub-normal range. So, there’s a yo-yo effect that goes with testosterone injections.

I encourage men to use either patches or preferably the gel formations. The reason I like the gel is that it has virtually no skin reactions, whereas the patches have a lot of skin reactions. My preference is for the testosterone gel. It is very, very well tolerated. It has virtually no adverse effects.

Hugo Verhoeven, MD: I think that was very, very interesting information. We learned quite a lot, thank you very much for this interview.

Joel M. Kaufman, MD: You’re very welcome.