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

Abstract

Hyperandrogenemia (HA) is a consistent reproductive phenotype in women with polycystic ovary syndrome (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. 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 with OB-g suggesting distinct etiologies of HA in affected girls. 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. Body mass index (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) (analysis of variance [ANOVA] P = 0.03; PCOS-d vs LC, P = 0.04; OB-g vs LC, P = 0.05; PCOS-d vs 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. Circulating 11KT levels were similarly elevated in peripubertal PCOS-d and OB-g, suggesting an adrenal component of HA in both groups. We found that 11-oxygenated 19-carbon steroid profiles did not identify subtypes of HA girls.