In the largest study ever conducted investigating disease risk and genetic sex hormone levels, researchers have found naturally high testosterone levels can confer significantly different effects between men and women, particularly in relation to type 2 diabetes.
The new research conducted a genome wide association study using data from over 400,000 subjects in the UK Biobank. Around 2500 genetic variants were identified relating to natural levels of the sex hormone testosterone.
In order to distinguish correlation from causation when looking at the associations between disease and testosterone levels, the researchers deployed a method called Mendelian randomization. This technique was developed as a way to weed out some of the more spurious conclusions often generated through associational studies. Essentially, the method hinges on our knowledge that certain genetic variants can influence the onset of certain diseases.
The results revealed higher genetic testosterone levels in women increased their risk of developing breast and endometrial cancers. Most significantly in women, higher testosterone levels were linked to a 51 percent increase in the risk of developing polycystic ovary syndrome (PCOS). In men higher natural testosterone levels were linked with increased risk for prostate cancer.
John Perry, from the University of Cambridge and joint senior author on the new study, suggests these particular associations between testosterone and disease have been previously detected, however, the nature of this research helps clarify a previously unclear causal relationship.
“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 Perry. "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.”
Perhaps the most compelling finding in the new research is the gender difference in type 2 diabetes risk relating to genetic testosterone levels. While genetically high levels of testosterone in women increased diabetes risk by 37 percent, in men high testosterone levels decreased risk of diabetes by 14 percent.
This particular finding is novel to the study and further research is surely necessary to verify a possible mechanism at play. Some scientists not affiliated with this study hypothesize the increase in diabetes risk for women relating to testosterone levels may be due to the influence the hormone has on increasing visceral fat.
Katherine Ruth from the University of Exeter, expressly notes it is too early to consider testosterone therapy as a treatment tool for any of the diseases identified in the research. Perhaps the most significant takeaway, Ruth suggests, is an affirmation of the differences in disease risk between men and women.
"Our findings provide unique insights into the disease impacts of testosterone,” says Ruth. “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."
The new research was published in the journal Nature Medicine.
Source: University of Exeter
