Androgen supplementation and risk for prostate cancer


A new paper from a research team in Seattle probably has limited relevance to our understanding of the real risks associated with androgen supplementation and subequent diagnosis of prostate cancer (or other prostate disorders) — even though it was a randomized, double-blind clinical trial.

Page et al. randomized 31 healthy men — all aged between 35 and 55 years — to daily treatment with a dihydrotestosterone (DHT) patch or a similar patch that contained a placebo for a period of 4 weeks. They then measured the impact on the patients’ serum and prostate tissue androgen concentrations and on the levels of expression of selected genes in the patients’ prostate epithelial cells.

Most readers will be aware that DHT, derived from local conversion of testosterone to DHT by 5α-reductase enzymes, is the androgen within the prostate that drives the growth of prostate (and prostate cancer) cells. We have known for years that if men are treated (or treat themselves) with testosterone or other androgen supplements,  that they have raised levels of serum DHT. What we have not  known is the impact of raised serum DHT levels on the prostate itself.

Here’s what Page et al. found after 4 weeks of treatment (i.e., in samples taken on day 28 of the study compared to pretreatment data):

  • 27/31 men completed all study procedures.
  • In men treated with transdermal DHT, serum DHT levels increased by nearly 700 percent but serum testosterone levels decreased.
  • In men treated with the placebo, serum DHT and serum testosterone levels were unchanged.
  • Intraprostatic DHT and testosterone concentrations were not different between the two groups of patients.
  • Prostate volume, PSA levels, epithelial cell proliferation, and androgen-regulated gene expression were not different between groups.

The authors conclude that abnormally high physiologic levels of serum DHT, associated with decreased levels of serum testosterone, “do not significantly alter intraprostatic levels of DHT, testosterone, or prostate epithelial cell androgen-regulated gene expression in healthy men.”

Now it is certainly true that this study shows that, “Changes in circulating androgen concentrations are not necessarily mimicked within the prostate microenvironment.” However, a study based on such a small number of men over such a short period of time may be of very limited significance when it comes to the long-term clinical impact of elevated androgen levels. All sorts of issues could effect that long-term impact. Did one of these 27 men have low-grade PIN before the study that has now converted to high-grade PIN? Did the intraprostatic levels of DHT “jump” within the first few days of treatment and then rebalance? If they did, what events might that effect have triggered? Four weeks is not exactly a significant time period in the development of prostate disorders — and most men who take androgen supplements take them for a ghood deal longer than 4 weeks.

The “New” Prostate Cancer InfoLink thinks this paper is scientifically interesting, but it is not a study on which we believe anyone should be making important clinical decisions about androgen supplementation and risk for prostate cancer.

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