In a new study, researchers found that having genetically higher testosterone levels increases the risk of metabolic diseases such as type 2 diabetes in women while reducing the risk in men.
Higher testosterone levels also increase the risks of breast and endometrial cancers in women and prostate cancer in men.
This is the largest study to date on the genetic regulation of sex hormone levels.
The research was led by the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge and the University of Exeter.
The team used genome-wide association studies (GWAS) in 425,097 UK Biobank participants to identify 2,571 genetic variations linked to differences in the levels of the sex hormone testosterone and its binding protein.
The researchers verified their genetic analyses in additional studies, including the EPIC-Norfolk study and Twins UK, and found a high level of agreement with their results in the UK Biobank.
The team next used an approach that 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 type 2 diabetes in men by 14%.
Additionally, they found that genetically higher testosterone levels increased the risks of breast and endometrial cancers in women, and prostate cancer in men.
The 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.
The findings show how genetic techniques such as Mendelian randomization are useful in the understanding of the risks and benefits of hormone therapies.
One author of the study is Dr. John Perry from the MRC Epidemiology Unit at the University of Cambridge.
The study is published in Nature Medicine.
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