Polycystic ovary syndrome after precocious pubarche:: ontogeny of the low-birthweight effect

Objective Young girls with precocious pubarche (PP) are at increased risk of developing polycystic ovary syndrome (PCOS), including hyperinsulinism, dysilpidaemia and ovarian hyperandrogenism, particularly if PP itself was preceded by a low birthweight. Resistance to insulin is thought to be a key factor in the pathogenesis of this sequence. We aimed to elucidate the peripubertal ontogeny of the low birthweight effect on hyperinsulinism, dyslipidaemia and ovarian dysfunction after PP. Patients and design We obtained fully longitudinal data from 51 girls with a history of PP and compared normal-birthweight (n=26) with low-birthweight (n=25) girls (birthweight SD score 0.0 +/-0.2 vs. -2.4 +/-0.2) for measurements obtained at diagnosis of PP (mean age 7.0 years), in early puberty (10.4 years) and after menarche (14.3 years). MEASUREMENTS Fasting serum lipids and lipoproteins, together with insulin responses to an oral glucose load, were assessed at diagnosis of PP, in early puberty and after menarche; serum gonadotropins were measured in early puberty and after menarche; ovarian function was examined postmenarche. Results Comparisons of endocrine-metabolic results between normal- and low-birthweight PP girls showed no detectable differences before puberty. The hypertriglyceridaemia and elevated LDL-cholesterol levels characterizing low-birthweight PP girls became detectable by early puberty; reduced insulin sensitivity was not evident until postmenarche, when the tendency to ovarian dysfunction also became obvious. Body mass indices of normal- and low-birthweight subgroups were identical in early puberty and postmenarche. Conclusions These longitudinal data show that, in PP girls, the endocrine-metabolic risk conferred by prenatal growth restraint is not readily detectable until puberty or postmenarche, and is not attributable to a higher body mass index.