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-oxyandrogens do not aid in the diagnosis of PCOS, they relate to excess hair growth. COCP treatment may related to 11-KT, however, further work is needed to determine causality, relationship with metabolic outcomes, and the clinical utility of measuring these androgens in PCOS.

Introduction: 11-oxygenated C19 steroids (11-oxyandrogens) have been shown to rise during adrenarche and remain higher throughout adulthood than in early childhood. The patterns of circulating 11-oxyandrogens throughout normal puberty has not yet been described. Methods: We conducted a secondary analysis of healthy youth participants, both males and females, enrolled in six prior endocrine studies (N=249). Participants were classified according to Tanner stage and body mass index (BMI). Concentrations of three adrenal-specific 11-oxygenated androgens, 11β-hydroxyandrostenedione (11OHA4), 11β-hydroxytestosterone (11OHT), and 11-ketotestosterone (11KT) were measured in fasting serum samples. Results: 11OHA4 and 11OHT increased modestly between early and late puberty in youth with normal weight (p < 0.05), whereas increases in 11KT did not reach statistically significance (p < 0.06). 11KT levels differed between sexes throughout puberty (p < 0.01), and changes in 11-oxyandrogens were small compared to the marked increases for estradiol in girls or testosterone in boys. The trajectories of 11KT and 11OHA4 changes throughout puberty differed by BMI category (p < 0.05). Conclusion: Beyond adrenarche, 11-oxyandrogens continue to rise during pubertal development. The differences in 11KT trajectories in males and females are small compared to changes in testosterone for males and estradiol for females during puberty. Obesity appears to influence the trajectories of 11-oxyandrogens during puberty.