Increased Adrenal Androgens in Overweight Peripubertal Girls

Abstract Context: Peripubertal hyperandrogenemia—a precursor to polycystic ovary syndrome—is prominent in girls with obesity. Objective: We examined sources of overnight testosterone (T) and progesterone (P4) and potential sources of obesity-associated hyperandrogenemia during puberty. Design: Cross-sectional. Setting: Research unit. Participants/Interventions: Fifty girls ages 7 to 18 years—both normal weight (NW) and overweight (OW)—underwent dexamethasone (DEX) suppression (1 mg orally; 10 pm) and cosyntropin stimulation testing (0.25 mg intravenously; 8 am the following day), with blood sampled before and 30 and 60 minutes after cosyntropin. Thirty-nine subjects receiving DEX had frequent blood sampling overnight (every 10 minutes from 10 pm to 7 am) and were compared with 70 historical controls who did not receive DEX. Outcomes: Random coefficient regression modeling assessed changes in hormone concentrations after DEX and cosyntropin. Results: NW early pubertal controls exhibited early morning increases in free T and P4 levels; NW and OW late pubertal controls exhibited early morning increases in P4. Such changes were not observed in subjects receiving DEX. Post-DEX morning free T levels were fourfold higher in OW vs NW late pubertal girls. Postcosyntropin changes in free T and androstenedione were both 2.3-fold higher in OW vs NW late pubertal girls. Conclusions: These data suggest that (1) overnight increases in free T and P4 concentrations in NW early pubertal girls and P4 concentrations in late pubertal girls are of adrenal origin and (2) OW late pubertal girls demonstrate elevated nonadrenal free T levels after DEX and exaggerated adrenal androgen (free T and androstenedione) responses to cosyntropin. Overweight late pubertal girls demonstrated higher free testosterone (T) after dexamethasone suppression and greater free T and androstenedione responses to cosyntropin stimulation.