9265 Racial/Ethnical Differences in Classic and 11-Oxygenated Androgens

Abstract Disclosure: C. Lee: None. R.J. Auchus: None. J. McDonald: None. J. Rege: None. W.E. Rainey: None. A.F. Turcu: None. Background: Malignancies modulated by sex-steroids, such as prostate and breast cancer, as well as disorders of androgen excess, like polycystic ovary syndrome, display prevalence and/or phenotype differences across races/ethnicities. Such differences have been attributed, in part, to testosterone (T). A set of adrenal-derived 11-oxygenated C19 steroids (11-oxyandrogens) has emerged as relevant to several androgen-dependent pathologies. Classic and 11-oxyandrogens are impacted differently by age and adiposity. Data on race and ethnic variations in 11-oxyandrogen concentrations are lacking. Setting and Participants: Participants in the population-based, multiethnic cohort of the Dallas Heart Study, phase 2. Measurements: T, androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4), 11β-ketoandrostenedione (11KA4), 11-hydroxytosterone (11OHT), and 11-ketotestosterone (11KT) were quantified simultaneously in peripheral blood using liquid chromatography-tandem mass spectrometry. Steroids were compared across races stratified by gender, and adjusted for age and BMI, using linear mixed models in SAS (NC, USA). Results: Of the 1966 participants included, 1137 (57.8%) were women, 49% were non-Hispanic Black, 35% non-Hispanic White, and 14% Hispanic. The mean age of study participants was 51.3 +/- 10.3 years, and mean BMI was 31.0 +/- 7.1 kg/m2. Compared to White individuals of similar age and BMI, 11KT concentrations were higher in both Black women (β = 3.5 +/- 1.2, p = 0.004), and Black men (β = 5.8 +/- 1.9, p = 0.002). The immediate precursor of 11KT, 11KA4, displayed higher concentrations in Black vs. White men (β = 2.9+/- 0.7, p 0.0001), with similar trends in women (β = 3.0 +/- 1.6, p = 0.056). The weak androgen 11OHT was higher in Black vs. White women (β = 3.0 +/- 0.91, p = 0.0009), but did not differ across races in men. Compared to White individuals of the corresponding gender, age- and BMI-adjusted 11OHA4 concentrations were higher in Hispanic women (β = 10.8 +/- 5.4, p = 0.043), and in Black men (β = 20.9 +/- 4.8, p 0.0001). The classic androgen T was higher in Black women and men (β = 3.7 +/- 1.4 and β = 41.5 +/- 14.7, respectively, p 0.01 for both), as well as in Hispanic men (β = 46.6 +/- 21.8, p = 0.03) compared to their White counterparts with similar age and BMI. A4 concentrations were similar across races. Conclusions: The bioactive androgens 11KT and T were higher in Black women and men compared to White individuals with similar age and BMI. Conversely, in Hispanic men, only T was higher compared to White men. In addition to T, 11KT might also contribute to disproportionately high prevalence of androgen-related pathologies in Black individuals. Acknowledgements: This work was supported by grant R01AG08051601 from the National Institute of Aging, and, in part, by grant UL1TR001105 from the National Center for Advancing Translational Science, National Institutes of Health. Presentation: 6/1/2024