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11-oxygenated C19 Steroids Do Not Distinguish the Hyperandrogenic Phenotype of PCOS Daughters from Girls with Obesity

Torchen, L.; Sisk, R.; Legro, R.; Turcu, A. F.; Auchus, R. J.; Dunaif, A.

J Clin Endocrinol Metab. 2020 Aug 17


CONTEXT: Hyperandrogenemia (HA) is a consistent reproductive phenotype in women with PCOS and their relatives. Increased testosterone levels are present in premenarchal daughters of affected women (PCOS-d). Obese girls (OB-g) without a family history of PCOS also have peripubertal HA. The sources and significance of HA in these groups remains unknown. OBJECTIVE: 11-oxygenated 19-carbon (C19) steroids are adrenally derived androgens that are elevated in hyperandrogenic disorders, including PCOS. We performed this study to test the hypothesis that peripheral serum 11-oxygenated steroids would differ in PCOS-d compared to OB-g suggesting distinct etiologies of HA in affected girls. DESIGN, SETTING, AND PARTICIPANTS: We compared peripheral serum 11-oxygenated steroid levels in 21 PCOS-d, 29 OB-g and 17 lean control girls (LC) of comparable age at an academic medical center. RESULTS: BMI differed by design (P<0.001). 11β-hydroxyandrostenedione, 11-ketoandrostenedione, and 11β-hydroxytestosterone levels did not differ between the groups. Compared with LC, PCOS-d and OB-g had similar elevations in 11-ketotestosterone (11KT) (ANOVA P=0.03; PCOS-d v LC, P=0.04; OB-g v LC, P=0.05; PCOS-d v OB-g, P=0.97). In multivariate regression, 11KT levels were associated with DHEAS (P=0.008), but not with BMI z score, breast Tanner stage, testosterone, anti-Müllerian hormone or sex hormone binding globulin levels. CONCLUSIONS: Circulating 11KT levels were similarly elevated in peripubertal PCOS-d and OB-g suggesting an adrenal component of HA in both groups. 11-oxygenated 19-carbon steroid profiles did not identify subtypes of HA girls.

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