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

Objective Young girls with precocious pubarche (PP) are at increased risk o f developing polycystic ovary syndrome (PCOS), including hyperinsulinism, d ysilpidaemia and ovarian hyperandrogenism, particularly if PP itself was pr eceded by a low birthweight. Resistance to insulin is thought to be a key f actor in the pathogenesis of this sequence. We aimed to elucidate the perip ubertal ontogeny of the low birthweight effect on hyperinsulinism, dyslipid aemia 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 measure ments obtained at diagnosis of PP (mean age 7.0 years), in early puberty (1 0.4 years) and after menarche (14.3 years). MEASUREMENTS Fasting serum lipi ds and lipoproteins, together with insulin responses to an oral glucose loa d, were assessed at diagnosis of PP, in early puberty and after menarche; s erum gonadotropins were measured in early puberty and after menarche; ovari an function was examined postmenarche. Results Comparisons of endocrine-metabolic results between normal- and low- birthweight PP girls showed no detectable differences before puberty. The h ypertriglyceridaemia and elevated LDL-cholesterol levels characterizing low -birthweight PP girls became detectable by early puberty; reduced insulin s ensitivity was not evident until postmenarche, when the tendency to ovarian dysfunction also became obvious. Body mass indices of normal- and low-birt hweight subgroups were identical in early puberty and postmenarche. Conclusions These longitudinal data show that, in PP girls, the endocrine-m etabolic risk conferred by prenatal growth restraint is not readily detecta ble until puberty or postmenarche, and is not attributable to a higher body mass index.