Infants of Women With Polycystic Ovary Syndrome Have Lower Cord Blood Androstenedione and Estradiol Levels

ABSTRACT Hyperandrogenemia is a characteristic feature of the polycystic ovary syndrome (PCOS) and contributes to pathogenesis. Animal model studies have demonstrated that maternal prenatal exposure to androgens produces a PCOS phenotype in offspring. The possible contribution of intrauterine androgen excess to the development of PCOS has been largely unexplored in human populations. The results of several prospective and retrospective studies of birth weight and growth restriction in PCOS are conflicting. Some studies have reported an association between PCOS and increased birthweight. In contrast, other studies have suggested that girls at risk for PCOS have low birth weight and that there is increased prevalence of small-for-gestational-age (SGA) offspring in women with PCOS compared with infants of reproductively normal control women. However, a meta-analysis of perinatal outcomes in PCOS, including only highly valid studies as well as 1 epidemiological, 1 prospective, and 3 retrospective studies were unable to confirm an association between PCOS and alterations in birth weight. The aim of this prospective case–control study was to investigate whether offspring of women with PCOS have alterations in fetal growth or show evidence for intrauterine androgen excess. The study subjects—PCOS women and their infants—included 39 PCOS and 31 control women who gave birth to 43 female (25 PCOS and 18 controls) and 27 male (14 PCOS and 13 control) infants. Mixed cord blood was available from 29 PCOS and 21 control infants for measurement of testosterone (T), dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, androstenedione (A), and estradiol (E2). Birth weight and prevalence of small-for-gestational-age and large-for-gestational-age (LGA) infants also were measured. No difference was found in the mean birth weight between the PCOS and control women, but a significant increase was found in the prevalence of LGA infants in the PCOS group (P < 0.05). Analysis of cord blood showed that E2 and A levels were lower (P < 0.05) in female PCOS compared to control offspring, but there was no difference in the T to E2 ratio between the groups. No significant difference was noted between the PCOS offspring and the appropriate control groups in E2 and A levels in male offspring or levels of 17-hydroxyprogesterone or other androgens (T, dihydrotestosterone, and dehydroepiandrosterone) in either male or female PCOS offspring. These findings provide no evidence for fetal growth restriction or intrauterine androgen excess among the offspring of women with PCOS. The data show that infants of women with PCOS were more likely to be LGA.