Testosterone therapy and the prostate

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Professor Dieter Jocham, MD and Christian Doehn, MD, Department Of Urology, University Of Schleswig-Holstein (UKSH) Campus Lubeck Medical School, Lübeck, Germany

What I’m dealing with is the interaction between testosterone and especially the prostate.

The role of testosterone in growth of the prostate, the testosterone levels and the correlation to BPH., testosterone substitution and consequences in that disease, testosterone levels and prostate cancer, which, to my thinking, is a very important part, and then the substitution and the consequences in case of prostate cancer. Also I will discuss a little bit about the effects of 5-alpha reductase inhibitors, and then come to a statement.

There is very clear evidence, among others from the Olmstead County study, that the prostate grows, regardless of the age, about 1.6% per year. Other authors claim for the range between .8% and 2%, so far.

If one looks into those studies it becomes clear that there is no difference of testosterone levels in the serum between men with, and without, BPH. And no BPH in men will arise if there is a long-term established lack of testosterone. On the other hand if you send a supply for testosterone you will identify normalisation of the prostate size, especially in hypogonadal men, but you will not induce an increase of the prostate.

If one looks for the testosterone substitution on one hand based on the transdermal procedure, and on the other hand on the intramuscular procedure, and if one compares the situation before the application of testosterone, to the one post-application, one can find there is no difference so far, even if you apply for the transdermal application instead of the intramuscular, and vice versa. This holds true also for the situation of PSA, there is no difference before and after the application of testosterone.

Is there any correlation between testosterone levels and  prostate cancer? It is a picture that is not really demonstrating one special situation. Probably there are different situations in the individual man. If you look for the studies you can find that there are studies demonstrating an increase in testosterone in cases of prostate cancer. Most of the patients on the survey have demonstrated to have an equal situation to healthy people. There are also papers demonstrating that there is a decrease of testosterone in patients in cases of prostate cancer.

If one looks not only to the testosterone with more or less a correlation in the index of one, but also to the non-serum globulin bound situation of testosterone, you find more or less the same situation. This also holds true for the DHT testosterone. If one looks into other parameters once more, one cannot identify differences comparing patients with prostate cancer to the healthy people.

What about the situation with hormone levels at all? If one looks into the data from Mohr and colleagues in the Massachusetts Male Aging study, there had been a survey of more than 1,500 patients. Those patients had been checked for several serum hormones, the androgens, the oestrogens, adrenal hormones and pituitary gland hormones. It was also then identified how much the risk of developing a prostate cancer in that group was in the following eight to ten years. That data has been corrected for age, body mass index, alcohol, DHT testosterone and PSA.

As a result, this study demonstrated that 4% of those patients in the follow up period developed a prostate cancer, which is quite a good correlation to the data from other studies. That study showed that there was no difference for people with, or without, prostate cancer as far as androgens had been concerned; all of them, the oestrogens, the adrenal hormones, and also FSH and LH and prolactin. The only difference, and this is not surprising to the urologists at least, has been that there is a difference in the PSA level, and the levels of free PSA, which in the case of prostate cancer was in the median 2.6 nanogram per ml compared to 0.7 in healthy men, and the relative percentage of free PSA was, in the case of prostate cancer, 11 instead of 15 in healthy men.

Much more important for the discussion is the question whether there could be a prostate cancer in use by testosterone? It is well known to everybody that hormones regulate the prostate growth. As I told you before, in hypogonadal men you will have small sizes of prostate, which will then change to normal size in the case of testosterone substitution. There are also experimental data that hypertestosteronemia induces prostate cancer in rats. It is also known that prostate cancer can be influenced negatively in growth by anti-hormonal treatment, or by androgen ablation. This is a very important point, up to now, there are no studies demonstrating that there is a prostate cancer induction by testosterone substitution itself.

What about 5-alpha reductase inhibitors? There is no doubt that there are effects on the prostate, but one has to recognise that the hypogonadal situation concerns the testosterone in serum, but not the intraprostatic testosterone. The intraprostatic testosterone is not heavily changed in case of prostate disease. It’s not correlated to the age of the patient. It’s very clear that DHT is the most active intraprostatic testosterone metabolite, and finasteride is involving the amount of the DHT within the prostate. By DHT it is possible to, if you lower it, reduce the size of the prostate up to 25%. There is also evidence that by applying for the finasteride it is possible to reduce the risk of prostate cancer, and in very recent studies up to 25%. There’s one side aspect, which is important to mention, those patients which nevertheless develop a prostate cancer following the finasteride therapy, will show up usually with high grade tumours.

So what, then, is the situation for giving substitutions? DRE and PSA have to be checked before the application of the therapy, and also during therapy. Suspected prostate and breast cancer are still absolute contraindications, and a sign of that also severe Bladder Outlet Obstruction should be in contraindication.

As far as we know today the endogenous and exogenous testosterone is probably without any effect on prostate cancer, but one has to deal very carefully with testosterone substitution in case of prostate cancer. Up to now it is a contraindication.

If we look for BPH there is obviously no significant increase in prostate size following the testosterone substitution. There is also no significant increase in PSA, which means that the follow up of those patients under testosterone substitution is not more difficult than in the normal situation. As far as we know from the clinical evaluations there are no impairments of voiding symptoms.

In general, as we all know, testosterone has a relatively high therapeutic range. The prostate is one of the most important targets to testosterone and this should then be translated to only normalising the testosterone level in the case of hypogonadism. One should use for better survey only drugs with short half life.