OR22-02 Sex Differences In 11-Oxyandrogen Correlations With Adipose Tissue Compartments

Abstract

Abstract Disclosure: A.F. Turcu: None. C. Lee: None. R.J. Auchus: None. Background: Adrenal-derived 11-oxygenated C19 steroids (11-oxyandrogens) are mediators of adrenarche and several disorders of androgen excess. 11β-hydroxyandrostenedione (11OHA4), a major adrenal product, is converted to the bioactive androgen 11-ketotestosterone (11KT) via 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) and aldo-keto reductase 1C3 (AKR1C3). The adipose tissue expresses both AKR1C3 and the type 1 isoenzyme HSD11B1, which participate in modulating peripheral androgen production. The impact of adipose tissue compartments on circulating 11-oxyandrogens in men and women is not well understood. Setting and Participants: A subset of participants in the population-based, multiethnic cohort of the Dallas Heart Study, phase 2 were included. Measurements: All participants underwent subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) measurements by abdominal magnetic resonance imaging (MRI). Testosterone (T), androstenedione (A4), and four 11-oxyandrogens were quantified simultaneously in peripheral blood using liquid chromatography-tandem mass spectrometry. Associations between adipose tissue compartments and androgens were assessed by Pearson correlation tests, stratified by sex. Results: Of the 498 participants included, 282 (56.6%) were women, 49% were Black, 32% White, 18% Hispanic. The mean age of study participants was 54.3 +/- 10.7 years, and mean BMI was 30.9 +/- 6.9 kg/m2. There was no difference in age and race distribution between men and women. 11OHA4, 11β-hydroxytestosterone (11OHT), and 11KT correlated positively with BMI in women (R2 = 0.15-0.18, p<0.01) but not in men. Conversely, T correlated negatively with BMI only in men (R2 = -0.26, p<.0001). 11OHA4 and 11OHT correlated directly with both SAT and VAT in women (R2 = 0.14-0.18, p<0.05), and a similar correlation was observed between 11OHT and VAT in men. Conversely, T and A4 displayed an inverse correlation with SAT and/or VAT in both sexes. 11KT and 11-ketoandrostenedione (11KA4) displayed no association with adipose tissue compartments. Conclusions: 11OHA4 and 11OHT, but not their respective 11-keto metabolites correlate with all adipose tissue compartments in women, while T correlates inversely with adiposity in men, particularly with SAT. Sexual dimorphism in adipose tissue and impact on androgen modulation might contribute to sex differences in cardiometabolic morbidity. Presentation: Saturday, June 17, 2023