Increased Adrenal Androgens in Overweight Peripubertal Girls

J Endocr Soc. 2017 Apr 12;1(5):538-552. doi: 10.1210/js.2017-00013. eCollection 2017 May 1.

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.

Keywords: adolescent, puberty; androgen; hyperandrogenemia; obesity.