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Background/context: Polycystic ovary syndrome (PCOS) is common and diagnosis requires an elevated testosterone. The clinical importance of adrenal 11-oxyandrogens in PCOS is unclear. We sought to determine if 11-oxyandrogens: 1) better identify PCOS diagnosis compared to testosterone 2) predict clinical comorbidities of PCOS, 3) are altered with combined oral contraceptive pill (COCP) or metformin therapy.

Methods: Data from 200 adolescent females aged 12-21 years, most with obesity, enrolled across 6 studies in pediatric endocrinology were included: 70 non-PCOS controls, 115 untreated PCOS, 9 PCOS+ obesity treated with COCP, 6 PCOS+ obesity treated with metformin. 11-hydroxyandrostenedione (11OHA4), 11-hydroxytestosterone (1-OHT), 11-ketotestosterone (11KT) and testosterone were measured with LC/MSMS. Data between 1) untreated PCOS and controls and 2) untreated PCOS and the 2 treatment groups were compared.

Results: Untreated girls with PCOS had higher 11OHA4 (p= 0.003) and 11OHT (p= 0.005) compared to controls, but not 11KT (p= 0.745). Elevated 11OHA4 remained significant after controlling for obesity. Testosterone better predicted PCOS status compared to 11-oxyandrogens (ROC analysis: 11OHA4 AUC= 0.620, 11OHT AUC= 0.638; testosterone AUC= 0.840). Among untreated PCOS, all three 11-oxyandrogens correlated with hirsutism severity. 11KT (p= 0.039) and testosterone (p< 0.006) was lower in those on COCP treatment compared to untreated PCOS). Metformin treatment had no effect on 11-oxyandrogens, although testosterone was lower (p= 0.01).

Conclusions/Relevance: While 11 …