Obesity, height, and serum androgen metabolism among postmenopausal women in the women's health initiative observational study

Background: Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers. Methods: Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures [current body mass index (BMI), waist-to-hip ratio (WHR), height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using LC-MS/MS. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use. Results: Regardless of HT use, higher current BMI (≥30 vs. <25 kg/m²) was associated with higher serum concentrations of dehydroepiandrosterone sulfate (DHEAS), 5a-reduced glucuronide metabolites [androsterone-glucuronide (ADT-G), 5a-androstane-3a,17b diol-3-glucuronide (3a-diol-3G), 3a-diol-17-glucuronide (3a-diol-17G)], and DHEAS:DHEA ratio (all P trend ≤ 0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all P trend < 0.001) but not among current users (P-int < 0.001). WHR was positively associated with adrenal androgens and 5a-reduced glucuronide metabolites in obese women only (BMI ≥ 30 kg/m²; all P-trend ≤ 0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5a-reduced glucuronide metabolites in never/former HT users (all P trend < 0.06). Height was not associated with androgen metabolites. Conclusions: Current BMI is associated with androgen metabolism among postmenopausal women. Impact: This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.