Insulin Resistance, Compensatory Hyperinsulinemia and its Role in Fetal Programming of Polycystic Ovarian Syndrome.

Polycystic ovary syndrome (PCOS) is a complex multifactorial polygenic disorder commonly affecting reproductive age women. Though its underlying causes are still unknown, insulin resistance (IR) and compensatory hyperinsulinemia that ensues is increasingly being shown to be an integral contributor to its pathogenesis. Further, recent evidence suggests that adverse intrauterine and early postnatal environment have significant long-term influence in the development of insulin resistance through developmental or fetal programming and could thus contribute to the development of PCOS. Therefore, this review will evaluate the role of insulin resistance in the pathogenesis of PCOS as well examine for evidence of its contribution to developmental programming of PCOS. An extensive PubMed and Science Direct database search was conducted. Relevant studies were identified using a combination of search terms: ‘Polycystic Ovary Syndrome’, ‘PCOS’, ‘Insulin resistance’, ’Compensatory hyperinsulinemia’, ‘Pathogenesis’, ‘Hyperinsulinism’, ‘Fetal or developmental programming’, ‘Hyperinsulinemic hyperandrogenism’ and ‘developmental hypothesis’ all in association with PCOS. The search was limited to articles published in English. One hundred and thirty seven papers were included for this review. Our findings revealed that excessive insulin results in hyperinsulinemic hyperandrogenism through action at various tissue levels which contributes to the pathogenesis of PCOS. There is evidence that gestational nutritional disturbances, gestational diabetes mellitus, maternal obesity and prenatal bisphenol-A (BPA) exposure predispose offspring to the development of PCOS mediated through induction of insulin resistance and compensatory hyperinsulinemia. In conclusion, intrauterine hyperinsulinemia contributes to the pathogenesis of PCOS and its prevention during these critical developmental periods may provide opportunities to decrease its burden or at the very least, halt progression of the disease and the complications associated with it later in life.