Prostate cancer is sensitive to testosterone. This has been known since the 1940s. Over the subsequent decades, testosterone suppression has become part of the routine treatment of metastatic prostate cancer. Modern medications can drive testosterone levels lower and lower, but eventually, the treatment method becomes ineffective.

    But prostate cancer develops in older men, when testosterone levels are low. If high testosterone levels cause prostate cancer, it would be more common in young men, but it is not. In fact, based on cell cultures and animal models, high levels of testosterone may have an anti-cancer effect.

    But how could the same hormone and the same androgen receptor on the cell have such different effects at different concentrations?

    A recent article shed some light on this topic. I’ve provided the article link, but because it is technical, I’ve also included a link to the explanation of the findings on the Duke website.

    As it turns out, when testosterone levels are low, the androgen receptor operates by itself, and its effect is to stimulate cell growth. But when testosterone levels are high, the androgen receptor works in pairs, joining up with another androgen receptor just like it. These androgen receptor complexes induce normalization of the cells, making the cell stop behaving like a cancer and start behaving like a normal prostate cell.

    This research was done in animal models and cell cultures. The results of high dose testosterone supplementation in patients with prostate cancer have been mixed. Sometimes it has been useful, sometimes not.

    This may be related to the way it was administered. Testosterone is not taken orally, because when it is, it is destroyed by the liver, and is toxic. When it is applied to the skin, it can be transferred accidentally to other people, or it can be unpredictably absorbed.

    The most common way to administer testosterone is via injection into a muscle as a large dose that gradually enters the circulation. The level is high initially, but drifts downwards. By the time the next dose is administered, the levels might have become low enough to stimulate cancer. Since many of the studies looking at testosterone administration in patients with prostate cancer used monthly injections, this may explain some of the ambiguity in their results.

    Please note that for patients who are on hormone blockade, simply stopping it is not a good idea. The body would start making testosterone again, but at a very low level that would be more likely to stimulate cancer growth. Disclaimer: these emails are not meant as medical advice. Speak to your personal physician before starting or stopping any medication or treatment.

    It will be interesting to see how the urology community uses these findings. As it stands, most urologists and indeed most doctors believe that in metastatic prostate cancer, testosterone needs to be as low as possible. But this study would suggest otherwise. Pharmaceuticals to drive testosterone down generate billions of dollars a year in sales in the USA.

    Finally, my thanks to Faiz Khan, MD, for sending me this study and for his editorial review of this email. I was a little surprised that I had not heard about this study before he sent it to me, since I get multiple emails from Medscape every day and review them all. I searched Medscape to see if they had covered this study. They had not, even though it was published in a good journal and the researchers are from Duke, a prestigious institution.