The Ontogeny of Distinct Reproductive Phenotypes in Girls at Risk for PCOS During the Postmenarchal Transition.

Abstract

Daughters of women with polycystic ovary syndrome (PCOS-d) and girls with overweight/obesity (OW-g) have hyperandrogenemia (HA) beginning in childhood. However, other features of their early reproductive phenotypes differ, suggesting that there are distinct mechanisms conferring increased risk for PCOS. We performed a cross-sectional study of adolescent girls during the early postmenarchal transition. PCOS-d (n = 15), OW-g (n = 12), and lean control girls (LC; n = 17) were studied within .2 to 1.2  years of menarche. Metabolic and reproductive phenotypes were assessed. SHBG levels were lower (P < .0001) in PCOS-d and OW-g vs LC. Free testosterone levels were higher (P = .02) in OW-g vs LC. dehydroepiandrosterone sulfate levels were higher (P = .04) in PCOS-d vs LC and trended higher in OW-g vs LC (P = .07). Morning LH levels were higher in PCOS-d vs OW-g (P = .02). LH and FSH responses to GnRH analog were also increased in PCOS-d vs OW-g (LH area under the curve (AUC) P = .006, FSH AUC P = .01). The prevalence of HA was similarly increased in PCOS-d and OW-g vs LC (χ2  P = .04). The prevalence of ovulatory dysfunction (menses >45 days or <21 days) was increased (χ2  P = .05) in PCOS-d vs OW-g and LC. Both PCOS-d and OW-g had persistent HA during the early postmenarchal transition. However, ovulatory dysfunction and neuroendocrine abnormalities, elevated basal, and stimulated LH responses to GnRH analog were observed only in PCOS-d. These findings support the existence of distinct developmental trajectories leading to polycystic ovary syndrome, with early neuroendocrine dysregulation in PCOS-d and peripheral, likely adiposity-related, androgen excess in OW-g.