High endogenous testosterone levels contribute to type 2 diabetes risk among young, healthy women
High plasma levels of endogenous total and circulating free testosterone are associated with a two- to sevenfold increased risk for developing type 2 diabetes among young, healthy women without comorbidities, according to findings from a large retrospective study published in the Journal of the Endocrine Society.
“The findings of this study suggest high plasma levels of testosterone could play a role in the pathogenesis of type 2 diabetes among women,” Jon Jarløv Rasmussen, MD, PhD, a specialist registrar and postdoctoral researcher in the department of endocrinology at Rigshospitalet in Copenhagen, Denmark, told Healio. “The incidence of type 2 diabetes was rather low in the study, but the results implicate that screening for type 2 diabetes among women with higher plasma levels of testosterone may be beneficial, even among women who are young and without established comorbidities, such as polycystic ovary syndrome.”
In a retrospective study, Rasmussen and colleagues analyzed data from 8,876 healthy women (mean age, 38.5 years) who provided blood samples to measure plasma testosterone, dehydroepiandrosterone-sulfate (DHEAS), dihydrotestosterone (DHT) and sex hormone-binding globulin (SHBG) between January 2007 and December 2015. Researchers analyzed androgens using tandem liquid-chromatography mass spectrometry. Researchers used Poisson regression models to calculate incidence rate ratios for developing type 2 diabetes during a median follow-up of 8.1 years, stratified by androgen quartiles.
During 69,728 person-years, 69 women received a type 2 diabetes diagnosis.
Researchers found that women in the highest quartiles for plasma total testosterone and calculated free testosterone were more likely to develop type 2 diabetes during follow-up vs. women in the lowest quartile, with IRRs of 1.97 (95% CI, 1.01-3.85) and 7.32 (95% CI, 2.84-18.83), respectively. Levels of SHBG were inversely associated with type 2 diabetes, whereas DHEAS and DHT were not associated with incident type 2 diabetes. Results persisted after adjustment for age, plasma SHGB and socioeconomic factors.
The researchers noted that there was limited information on the body composition and BMI of the women analyzed for the study.
“Interestingly, a recent study demonstrated that endogenous androgens are inversely related to BMI in healthy women,” the researchers wrote. “In line with this, we noted plasma SHBG was lowest among women in quartile 1 and highest among women in quartile 4 of plasma total testosterone. Thus, suggesting that women in the lowest quartile of plasma total testosterone could feature highest insulin resistance and BMI at baseline, while women in the highest quartile of plasma total testosterone potentially feature lowest insulin resistance and BMI. Accordingly, we may have underestimated, rather than overestimated, the influence of testosterone on the risk of developing type 2 diabetes in women.” – by Regina Schaffer
For more information:
Jon Jarløv Rasmussen, MD, PhD, can be reached at the Department of Endocrinology, University Hospital of Copenhagen, Rigshospitalet, Ole Maaløes Vej 24, opg. 7562, DK-2200, Denmark; email: jon.ras@dadlnet.dk; Twitter: @JonRasmussen9.
Disclosures: The authors report no relevant financial disclosures.
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This study strongly supports a need for greater understanding of the association between SHBG and type 2 diabetes risk. These findings suggest that testosterone levels are not associated with type 2 diabetes risk among women; there were no between-group differences among women with testosterone levels in the first, second and third quartiles. However, risk is unequivocally reduced for any women in this cohort with an SHBG level above the lowest quartile.
This study also lacks data on BMI and smoking status. Women who smoke have higher total testosterone levels than women who do not smoke, and smoking is associated with cardiometabolic disease risk. Additionally, in Denmark in 2010, between 15% and 20% of women were smokers, and this percentage may have been higher in 2007. Furthermore, there was no adjustment or comment on menopause status. The average age at menopause is 51 years, and 10% of women begin menopause before age 45 years. Menopause is associated with an increased risk for development of type 2 diabetes. Data on use of hormone replacement therapy, which increases SHBG level and lowers testosterone, is also worth considering.
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