Δ⁵-Androstene-3β,17β-diol in healthy eumenorrheic women: Relationship to body mass and hormonal profile

Objective: To determine whether Δ⁵-Androstene-3β,17β-diol or androstenediol secretion increases with body mass. Design: A prospective study. Setting: University-based clinical research center. Patients: Twenty healthy, nonhirsute, eumenorrheic women, 10 with a body mass index (BMI) 31 kg/m² and 10 with a BMI > 31 kg/m² were studied. Interventions: All patients had blood sampled before (0 minute) and 60 minute after acute administration of 1 mg ACTH-(1-24) IV. Body circumferences were obtained, and the BMI and waist-hip ratio was calculated. Main Outcome Measures: Total T, androstenedione (A), E₂, sex hormone binding globulin, DHEA, DHEAS, and androstenediol were measured at 0 minutes (steroid₀); and DHEA, A and androstenediol were also measured after stimulation (steroid₆₀). The net steroid increment (Δ) from 0 to 60 minute was calculated. Results: Compared with thin women, obese subjects had higher levels of androstenediol₆₀ (95.8 ± 20.3 versus 130.7 ± 40.7 ng/dL, respectively [conversion factor to SI units, 0.03443]) and Δandrostenediol (17.4 ± 8.7 versus 37.8 ± 29.0 ng/dL, respectively [conversion factor to SI units, 0.03443]). Neither the BMI, height, nor the body circumference measures correlated with any of the steroid levels or responses to adrenal stimulation, except for a weak positive correlation between BMI and estrone (E₁) (r = 0.38) and a negative correlation between waist-hip ratio and Δandrostenediol (r = -0.51). The basal level of T, E₁, and DHEA₀, but not A or DHEAS, correlated with androstenediol₀ (r = 0.65, 0.62, and 0.67, respectively) and Δandrostenediol (r = 0.66, 0.63, and 0.63 to 0.005, respectively). Conclusions: Although the unstimulated morning androstenediol level did not differ between obese and thin euandrogenic healthy women, the response of androstenediol to ACTH-(1-24) stimulation was greater in obese individuals. The present findings, together with our previous data demonstrating an increased adrenal secretion of the E₁ precursor A in response to ACTH in obese women, suggests that the adrenal cortex in overweight women may further enhance the estrogenic milieu of these women.