Until recent years it was long-held by the medical profession that testosterone therapy increases the risk of prostate cancer. A recent study, however, shows that not only does testosterone therapy not raise prostate cancer risk, it actually lowers aggressive prostate cancer by 50%. Yes, testosterone can lower prostate cancer risk. This is big news when you consider that one in seven men now get prostate cancer (a higher percentage than the number of women who get breast cancer) and most men eventually become testosterone deficient, at least clinically. It is also the second leading cause of cancer death in men next to lung cancer.
The findings of the recent study are not surprising to those of us who routinely treat men for testosterone deficiency. Smaller studies suggested that testosterone might lower the risk for more aggressive prostate cancer. Morgentaler conducted a small study on 13 men with low-grade prostate cancer and low testosterone that was published in Journal of Urology in 2011 in which the prostate cancer was left untreated and the men treated with testosterone. The men’s prostate glands were biopsied before and after the study. The mean time of testosterone therapy was 2.5 years. No cancer was seen in 54% of the follow-up biopsies. There was no progression of cancer and no distant disease was seen.
The new study was presented at the American Urological Association’s Annual Meeting on May 9, 2016 and was conducted by Stacy Loeb, MD, and et. al. from NYU Langone Medical Center. The study analyzed data on approximately 250,000 men from Sweden obtained from the country’s nationwide registry. The study found that men treated with testosterone for over a year showed no increase risk in developing prostate cancer and their risk of developing aggressive prostate cancer was 50% lower than men not treated with testosterone.
The Myth: Testosterone Causes Prostate Cancer
The position that testosterone causes prostate cancer never made sense intuitively as prostate cancer is almost exclusively a disease of middle-aged and elderly men who have declining testosterone levels and rarely affects males with the highest testosterone levels – teenagers and 20 year olds. Sixty percent of prostate cancers are diagnosed in men 65 or over and it is rare before age 40 (American Cancer Society).
So why was it felt that by the medical profession that testosterone increases risk of prostate cancer? There are two key studies that linked testosterone to prostate cancer. The first was published in 1941 by Huggins and Hodges on three patients with metastatic prostate cancer who were given testosterone. Note: they already had prostate cancer. Not only that, but the cancer had spread to other parts of the body.
One patient was lost to follow-up. One patient showed no progression of his metastatic prostate cancer. One patient did show progression based on a laboratory test no longer used. That man had been previously castrated as it was known that castration and removal of testosterone led to a shrinkage (regression) of prostate cancer. From that case study Huggins concluded that testosterone can enhance growth of prostate cancer in metastatic disease. There is nothing wrong with his conclusion. But, over the subsequent years some how that got translated into testosterone causes prostate cancer even though other studies throughout the following decades suggested that it did not.
Also,the fact the castration leads to regression of prostate cancer seemed to support the notion that “adding” testosterone would raise prostate cancer risk.
The second key study was published in 1981 by Fowler and Whitmore at Sloan-Kettering Memorial Hospital. They administered testosterone to 52 men who also had metastatic prostate cancer prior to testosterone therapy. Forty-five of those men had an unfavorable response to testosterone therapy. Of the 52 men 48 had been castrated either surgically or medically.
OK, Dr. Joe that is three times you mentioned castration. Why is that important to this discussion? Here’s why castration muddies the water and matters. For testosterone to work there have to be receptors on the cell to receive testosterone and transport it into the cell. Marks and colleagues discovered that testosterone receptors in the prostate gland are saturated (fully occupied) at relatively low levels of testosterone and reported their findings in JAMA 2006. Morgentaler later dubbed this the saturation model. Once testosterone levels are above this threshold it has no additional effect on prostate growth.
When a man is castrated his testosterone levels fall to zero or near zero. If you then introduce testosterone to his prostate gland testosterone will fuel further prostate growth known as a “testosterone flare”. However, if you introduce testosterone to men with prostate cancer with testosterone above this threshold there is no further prostate growth. There is a saturation point which is now felt to be a serum testosterone level of 250 ng/dl above which testosterone has no growth effects on the prostate gland. Below that threshold adding testosterone can fues prostate growth.
The saturation model explains why castration leads to prostate cancer regression, but raising testosterone above the magical threshold does not increase prostate cancer rates. So testosterone does cause prostate tissue growth but only up to a certain level of testosterone (250 mg/dl). So a testosterone level of 700 ng/dl causes no more prostate growth than a level of 420 ng/dl or 251 ng/dl but will cause more prostate growth than a level of 150 ng/dl.
Recently, more studies are linking low testosterone to more aggressive prostate cancer. At this time it appears that prostate cancer in the face of a normal testosterone level is a better scenario than prostate cancer in association with low testosterone all other factors being the same.
This would seem to provide motivation to treat symptomatic androgen deficient men with testosterone therapy before their levels dip below 250 ng/dl to alleviate symptoms and to lower prostate cancer risk.
In the urologic world is has now become increasingly accepted that testosterone does not cause prostate cancer, though the myth that it does persists outside the urologic arena.
Testosterone and Heart Disease
Some physicians are still concerned that testosterone can increase risk of heart disease and we have addressed that in our own articles – article 1, article 2, article 3, article 4, and article 5. In 80 years since testosterone therapy began and after hundreds of studies looking at testosterone and the cardiovascular system there are only four studies suggesting testosterone might increase cardiovascular events. And, they all have serious study flaws.
Here is something to consider, and you don’t need science to answer this. The heart is a muscle. Like other muscles in the body the heart contains receptors for testosterone. In fact, the heart contains the highest concentration of testosterone receptors in the body – period. This seems well intended as the heart is a muscle that contacts every second (hopefully) unlike other muscles. Would that be the case if testosterone was dangerous to the heart?