A recent international consensus led to publication of a position statement that says that women should not be using testosterone for any condition other than post-menopausal low sexual desire, and even then, doses should be kept low, and the patients must be constantly monitored by their doctors. A study published in the February 10, 2020, issue of Nature Medicine (and led by researchers from the Medical Research Council Epidemiology Unit at the University of Cambridge and the University of Exeter) looked at another angle: the effect of genetically high testosterone on the risk of certain diseases in men and women.

Naturally High Testosterone Levels Are Linked to Risks for Disease in Men vs. Women

The research team used genome-wide association studies (GWAS) of 425,097 Britons, and after that employed what is called a Mendelian randomization, which looks at genetic differences to figure out if associations between genetically higher testosterone levels and disease are causal rather than correlative. Results:

In women, higher testosterone increases the risks of type 2 diabetes by 37 percent, and polycystic ovary syndrome (PCOS) by 51 percent.In men, higher testosterone levels reduce type 2 diabetes risk by 14 percent.Higher testosterone levels increase the risks of breast cancer and endometrial cancer in women, and prostate cancer in men.

Findings Further Understanding of the Risks of Genetically High Testosterone

In announcing the study, John Perry, MD, joint senior author on the paper, of the MRC Epidemiology Unit at the University of Cambridge, said: “Our findings that genetically higher testosterone levels increase the risk of PCOS in women is important in understanding the role of testosterone in the origin of this common disorder, rather than simply being a consequence of this condition. “Likewise, in men, testosterone-reducing therapies are widely used to treat prostate cancer, but until now it was uncertain whether lower testosterone levels are also protective against developing prostate cancer. Our findings show how genetic techniques such as Mendelian randomization are useful in understanding of the risks and benefits of hormone therapies.”

Caution: The Importance of Separating the Sexes

In the study announcement, Katherine Ruth, MD, the other lead author, of the University of Exeter, added: “Our findings provide unique insights into the disease impacts of testosterone. In particular they emphasize the importance of considering men and women separately in studies, as we saw opposite effects for testosterone on diabetes. Caution is needed in using our results to justify use of testosterone supplements, until we can do similar studies of testosterone with other diseases, especially cardiovascular disease.”

When Dr. Perry was asked for a hypothesis for the relationship, he wrote in an email, “It’s quite surprising that the same molecule can increased the risk of [metabolic] disease in women but reduce it in men. [For the cancer association], that could potentially be attributed to the downstream conversion of testosterone to estrogen that takes place in the body, which is well known to fuel tumor growth. At this stage we don’t really have a clear hypothesis as to why this is the case, but it’s something we’ll be looking into moving forward.”

Study Raises New Concerns About Testosterone Therapy

“Based on this information, this raises the question about patients and doctors needing to be cautious when taking supplemental testosterone,” said Robert M. McLean, MD, president of the American College of Physicians and medical director at Northeast Medical Group of Yale New Haven Health in Connecticut. “We just don’t know what we don’t know. Previous data did not suggest that there was an increase in prostate cancer in men who took testosterone, but those were limited, small studies. This study is not definite, but it opens the way for further testing. People should not be taking testosterone lightly and certainly not without monitoring, as we don’t know for sure about the possibility of significant harms.”