Testosterone Levels Affect Risk of Diabetes and Cancer

In a study of the genetic regulation of sex hormone levels, researchers found that the level of testosterone in men and women changes their risk of certain diseases. For example, increased testosterone increases the risk of metabolic diseases like type 2 diabetes in women but reduces the risk in men. Higher testosterone levels also increase the risks of breast and endometrial cancers in women as well as prostate cancer in men. The findings were published today in Nature Medicine.

“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,” says first author Katherine Ruth of the University of Exeter.

Despite finding a strong genetic component to circulating testosterone levels in men and women, the authors found that the genetic factors involved were very different between the sexes. Additionally, the researchers used genome-wide association studies to identify genetic variations associated with differences in the levels of the sex hormone testosterone and its binding protein sex-hormone binding globulin (SHGB).

To get their results, the team used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to understand whether known associations between testosterone levels and disease are causal rather than correlative. They found that in women, genetically higher testosterone increases the risks of type 2 diabetes by 37% and polycystic ovary syndrome (PCOS) by 51%. However, they also found that having higher testosterone levels reduces T2D risk in men by 14%. Additionally, the researchers found that genetically higher testosterone levels increased the risks of breast and endometrial cancers in women as well as prostate cancer in men.

“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,” says senior author John Perry of the University of Cambridge. “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.”