Associations of Total Testosterone with Cardiometabolic Biomarkers among Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) affects 6–12% of women of reproductive age in the United States. Women with PCOS are at a higher risk of experiencing cardiovascular and metabolic diseases such as diabetes; however, mechanisms linking PCOS to the development of diabetes remain unclear. This study aimed to investigate the association of total testosterone with cardiometabolic risk factors among women with PCOS and the potential effect modifying role of obesity. Methods: A retrospective cross-sectional study was conducted using data extracted from the medical records of women attendants (2014–2021) of the University of Washington Endocrinology Clinical and Diabetes Institute. Participants (n=170) were 18–50 years old and met at least two Rotterdam criteria for PCOS: Irregular menstrual periods, elevated androgen levels, and the presence of polycystic ovaries on an ultrasound. Blood samples were collected for biomarker measurements. Unadjusted and adjusted (for age, smoking, and race) regression models were used to examine associations of total testosterone with glucose metabolism biomarkers (fasting glucose, fasting insulin, hemoglobin A1C [HbA1c], and Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] and lipid biomarkers (HDL-c, LDL-c, total cholesterol, and triglycerides). Additionally, we examined whether associations differed in women with and without obesity, defined by a body mass index (BMI) ≥30 kg/m2. Results: The average total testosterone of participants was 65.36 ng/dL (SD=27.14 ng/dL). Overall, we found no significant associations of total testosterone with glucose metabolism biomarkers or lipid biomarkers. There was some suggestive evidence that associations of total testosterone with lipid biomarkers differed by obesity status although association estimates from obesity-stratified models did not reach statistical significance: Among participants without obesity, total testosterone was inversely related to LDL-c (adj. β=-0.229; 95% CI: -0.551,0.093) and total cholesterol (adj. β=-0.296; 95% CI: -0.717, 0.125), while among participants with obesity, total testosterone was positively related to LDL-c (adj. β=0.096; 95% CI: -0.232,0.424) and total cholesterol (adj. β=0.101; 95% CI: -0.289,0.491) (p for interaction > 0.05). Conclusion: We found no evidence for overall associations between total testosterone and cardiometabolic biomarkers, contrary to previous reports of associations between elevated androgen and cardiometabolic risk. We found suggestive evidence that obesity may modify associations of total testosterone with lipid levels. Future research using prospective study designs and careful phenotyping is needed to understand factors contributing to cardiometabolic disease among women with PCOS.