Higher levels of a male sex hormone increase the risk of diseases such as type 2 diabetes in women, while reducing the risk in men, new research suggests.
Genetically higher testosterone levels also increase the risks of breast and endometrial cancers in women, and prostate cancer in men, scientists say.
The findings come from what is believed to be the largest study to date on the genetic regulation of sex hormone levels.
Researchers found the genetic factors involved were very different between the sexes, despite finding a strong genetic component to circulating testosterone levels in men and women.
Dr John Perry, from the MRC Epidemiology Unit at the University of Cambridge and joint senior author on the paper, 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 randomisation are useful in understanding of the risks and benefits of hormone therapies.”
The study, published in Nature Medicine and led by researchers from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge and the University of Exeter, used genome wide association studies (GWAS) in 425,097 UK Biobank participants.
They identified 2,571 genetic variations associated with differences in the levels of the sex hormone testosterone and its binding protein sex-hormone binding globulin (SHGB).
They verified their analyses in additional studies, and found a high level of agreement with their results.
The team next 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.
According to the study, genetically higher testosterone levels in women increase the risks of type 2 diabetes by 37%, and polycystic ovary syndrome (PCOS) by 51%.
However, they found that having higher testosterone levels reduces type 2 diabetes risk in men by 14%.
Additionally, they found genetically higher testosterone levels increased the risks of breast and endometrial cancers in women, and prostate cancer in men.
Dr Katherine Ruth, of the University of Exeter – one of the lead authors of the paper, added: “Our findings provide unique insights into the disease impacts of testosterone.
“In particular they emphasise the importance of considering men and women separately in studies, as we saw opposite effects for testosterone on diabetes.”
However, she warned that caution is needed in using the results to justify use of testosterone supplements, until similar studies can be conducted on testosterone with other diseases, especially cardiovascular disease.