SUN-470 - Longitudinal Associations of Classic and 11-Oxygenated Androgens with Cardiovascular Disease (CVD) Risk Factors in Women in CARDIA (Coronary Artery Risk Development in Young Adults)

Introduction: Few studies evaluate the longitudinal relationships between adrenal 11-oxygenated androgens and CVD risk factors.

Methods: We examined associations between androgens and CVD risk factors in 455 women in CARDIA, a longitudinal cohort of Black and White participants followed from young adulthood into midlife. Testosterone [T], androstenedione [A4] and 11-oxyandrogens (11-hydroxytestosterone [11OHT], 11-ketotestosterone [11KT], 11-hydroxyandrostenedione [11OHA4], and 11-ketoandrostenedione [11KA4]) were quantified by liquid chromatography mass spectrometry from plasma at the Y2 and Y25 exam when women were approximately 28 and 51 years of age. Generalized estimating equations were used to evaluate longitudinal associations between androgens and CVD risk factors at Y2 and Y25 exams, with the exception of glucose and insulin which were measured at baseline and Y25 exams. Each CVD risk factor was used as the outcome and each androgen as the primary independent variable in separate models. Glucose was dichotomized (≥100 vs < 100 mg/dL) in logistic models, while other CVD factors were examined in linear models. Mean arterial blood pressure (MAP), insulin, and triglycerides were log-transformed, with results expressed as percentage changes. Models adjusted for age, race, center, body mass index (BMI), oral contraceptive (OCP) use, estrogen use, and gynecologic surgery (hysterectomy and/or oophorectomy) at each exam year.

Results: 11-oxyandrogens were associated with blood pressure, elevated fasting glucose, and lipids. With each 10 ng/dl increase in 11KT (0.7%, 95% CI 0.2%, 1.2%, p=0.004), 11OHA4 (0.2%, 95% CI 0.1%, 0.4%, p=0.004), and 11KA4 (1.5%, 95% CI 0.4%, 2.7%, p=0.01), MAP was higher. For each 10 ng/dl increase in 11KT (odds ratio [OR] 1.2, 95% CI 1.1, 1.5, p=0.009), 11OHT (OR 1.5, 95% CI 1.1, 2.2, p=0.02), 11KA4 (OR 1.5, 95% CI 1.1, 2.1, p=0.008) and 11OHA4 (OR 1.05, 95% CI 1.00, 1.09, p=0.03), odds of elevated fasting glucose was higher. For each 10 ng/dl increase in 11OHT (-4.0%, 95% CI -7.8%, -0.1%), triglycerides were lower. No other associations were observed between 11-oxyandrogens with insulin or lipid subfractions. Associations persisted after adjustment for T and when restricted to women not using OCP or estrogen. T and A4 were not associated with risk factors except each 10 ng/dl increase in T was associated with lower triglycerides (-2.3%, 95% CI -4.4%, -0.2%, p=0.03). Free androgen index was associated with higher log-MAP (0.009, 95% CI 0.002, 0.016, p=0.01), log-insulin (0.072, 95% CI 0.040, 0.104, p< 0.001), low-density lipoprotein cholesterol (2.05, 95%CI 0.04, 4.07, p=0.046), and odds of elevated glucose (OR 1.29, 95%CI 1.04, 1.60).

Conclusion: Higher 11-oxyandrogens (11KT, 11OHA4, 11KA4) were associated with higher blood pressure and higher odds of elevated glucose in women from adulthood to midlife. These steroids may contribute to CVD risk in women.