High Levels of Testosterone Affect Women and Men Differently

with Anna Murray, PhD, and Mark E. Molitch, MD

Having a high level of circulating testosterone actually impacts the health of men and women in notably different ways,1 according to evidence gathered by a team of international researchers.

While you are likely to consider testosterone as a ''man's" hormone, this naturally occurring sex hormone is actually produced in the bodies of both women and men. The difference is in the levels that are present.

High Testosterone affects the health of men and women different.Examining genetic factors shed light on the different effects that high testosterone can have on the health of men and women. Photo: fotostorm @ iStock

Supplemental testosterone may be required to correct low levels in order to regulate bone health, sexual performance, and body composition (ie, lean muscle), but the actual effects on the risks and outcomes of chronic diseases have not been confirmed.

So, a team of investigators from the University of Exeter College of Medicine and Health in the United Kingdom (UK) and numerous other institutions, including the United States, evaluated testosterone levels and genetic data available from more than 425,000 patients in the UK Biobank.

What Is the Precise Impact that Testosterone Has in the Health of Both Sexes?

Study co-author, Anna Murray, PhD, an associate professor in human genetics at the University of Exeter, and her colleagues took a look specifically at more than 2,500 genetic variables that regulate testosterone and identified diverse effects that different testosterone levels had on men and in women in terms of the impact on disease risk.

They concluded that having a higher testosterone level appears to increase the risk of developing metabolic diseases such as type 2 diabetes in women but proves beneficial in reducing that same disease risk in men.1

"We've shown that testosterone levels in men and women are heritable [transmissible from parent to child] and influenced by the combined effect of many genetic variants and genes," says Dr. Murray. "Notably, testosterone levels are regulated completely differently in each of the sexes."

High Testosterone Works Positively in Men and Negatively in Women

The researchers evaluated a wide range of genetic variables to help explain cause-and-effect relationships between testosterone levels and health. "Higher testosterone appears protective of metabolic diseases such as type 2 diabetes in men," Dr. Murray told EndocrineWeb, "but increases the risk of diabetes and polycystic ovary syndrome (PCOS) in women."

The effect on women is not really a surprise, as PCOS is a hormonal disorder that commonly occurs among women of child-bearing age. Those affected may have prolonged or infrequent menstrual periods, among other symptoms, and are found to have excess male reproductive hormone levels. Long-term complications of PCOS include an increased risk of developing type 2 diabetes and heart disease.

Having a higher testosterone level in women boosts their risk of type 2 diabetes by 37%, says Dr. Murray, and increased the risk of having PCOS by 51%.1 These types of chronic disease risks are reversed in men who have normally higher levels of testosterone who tend to have a decreased risk (by 14%) of type 2 diabetes.1

However, it’s not all good news for men, either. An elevated level of testosterone raises the risks of certain hormone-sensitive cancers in both sexes. "We also found higher levels of testosterone increased the risk of prostate cancer in men and hormone-sensitive cancers in women," she said. Among the hormone-sensitive cancers are breast and endometrial.1

Genetics Influences the Way Testosterone Affects Health

There was a surprising finding uncovered by this work, Dr. Murray says, which was ''the completely different genetic regulation of testosterone in men and women.1 It shows that we need studies and analysis that adequately consider both biological sexes."

"It was interesting to find that testosterone levels are a risk factor for developing prostate cancer in men. We’ve known that [hormone] therapy to lower testosterone is useful to treat these men but there has been an ongoing debate about whether it alters the risk of developing prostate cancer,” she says. Now we have some evidence of this.1

The discovery that testosterone impacts the chance that women will develop polycystic ovary syndrome was also unexpected. "The prevailing thought has been that elevated testosterone was solely the consequence of the disease, but our research suggests that testosterone may also play a direct role in disease susceptibility."

Building on Longstanding Knowledge of the Role of Reproductive Hormones

Testosterone therapy has well known positive effects, which have been proven randomized controlled trials on sexual functioning, muscle strength, bone mineral density, among other areas of health.2

As has been mentioned, a high level of circulating testosterone is known to promote the growth and spread of prostate cancer, perhaps even increasing a man’s susceptibility to future risk of prostate cancer.3-5

However, research results, to date, that have tried to show the influence of testosterone on type 2 diabetes or heart disease have failed to do so scientifically.6 Similarly, studies on the direct effects of testosterone on blood sugar control in men and PCOS in women have been insufficient, too.7-10

For that reason, these researchers decided to focus on the possible role of genetic variations on testosterone levels and how these gene differences may influence sex hormone traits and health in men and women.1

Not Reason Yet to Consider Lowering Testosterone to Improve Health Outcomes

Mark E. Molitch, MD, professor emeritus in the division of endocrinology, metabolism and molecular medicine, at Northwestern University Feinberg School of Medicine, in Chicago, Illinois, who was not involved in the reseach agreed to review the study for EndocrineWeb.

While the genetic information and disease associations uncovered by these researchers is new, Dr. Molitch says, the risks are nothing new. "We already know that there are risks related to testosterone administration in men and women and that the condition of polycystic ovary syndrome is associated with increased testosterone levels and increases the risk for diabetes [in women]," he tells EndocrineWeb.

When asked for what reasons men and women might consider taking action to adjust their level of testosterone, Dr. Murray says: "We don't recommend that anyone take medications to alter testosterone levels on the basis of our findings."

Yet, she adds, there is ''already great interest in the use of testosterone supplements, and widespread prescriptions for this hormone– so our findings should inform those already taking or considering use of such hormones.“

“In women, for example, testosterone appears to be harmful for increasing the risks of metabolic diseases and some cancers. In men, the situation is more complex: There is clearly a trade-off when considering [testosterone] treatment in men with a reduction in metabolic health risk but increased susceptibility to prostate cancer. And, we need more data to understand the role of testosterone in heart disease."

Guidelines about which men with low testosterone levels might benefit by receiving supplemental testosterone therapy have been issued by at least four organizations, including the Endocrine Society, the American Urological Association, the International Society for the Study of the Aging Male, and the International Society of Sexual Medicine.11

The guidelines approach the need for and benefits of testoerne replacement therapy with differing points of view that are bound to change as more data accumulates. For instance, the Endocrine Society recommendation emphasizes the results of recent clinical trials, noting there is ''continuing uncertainty about the benefits and risks of testosterone therapy" in men with documented low [androgen hormone] levels.2

Neither Dr. Murray nor Dr. Molitch have relevant financial conflicts regarding this work.  

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