06/06/2006 – The Practical Management of Childhood Obesity

Professor Stephen Franks, Professor of Reproductive Endocrinology, Imperial College, London, UK
E-mail: s.franks@imperial.ac.uk

Polycystic ovary syndrome (PCOS) frequently presents during adolescence and is the commonest cause of menstrual irregularity and hirsutism. The characteristic endocrine abnormalities include hypersecretion of androgens and LH. Metabolic dysfunction is also a feature of many young women with PCOS. Hyperinsulinaemia and insulin resistance, which can be regarded as an exaggeration of the normal metabolic changes that occur during puberty, are further amplified by obesity. It is of concern that adults with symptoms of PCOS who have the most unfavourable metabolic profile are those who were obese as children. The aetiology of PCOS is uncertain but there is evidence for a primary abnormality of ovarian androgen production which is manifest at puberty but may have its origins in childhood or even during fetal development. We have recently proposed that polycystic ovary syndrome has its origin in fetal life. This hypothesis is based on data from animal models (Rhesus monkey or sheep that have been exposed prenatally to high doses of androgen) and is supported by clinical studies. It is suggested that, in human females, exposure to excess androgen, at any stage from fetal development of the ovary to the onset of puberty, leads to many of the characteristic features of PCOS, including abnormalities of LH secretion and insulin resistance. It is likely that, in humans with PCOS, the development of the PCOS phenotype results primarily from a genetic predisposition for the fetal ovary to hypersecrete androgen. At present, it is unclear whether the maternal environment directly influences the development of PCOS in the offspring. Maternal androgen excess is unlikely to affect the fetus, because the placenta presents an effective barrier, but metabolic disturbances during pregnancy could affect development of the syndrome in the fetus. In postnatal life the natural history of PCOS can be further modified by factors affecting insulin secretion and/or action, most importantly, nutrition.

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