INSULIN ACTION IN THE NORMAL AND POLYCYSTIC OVARY

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and hirsutism.1, 22 In addition to the reproductive consequences of the syndrome, PCOS is characterized by a metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features.9, 21 The characteristic disturbances of insulin secretion and action are much more prominent in women with PCOS with amenorrhea or anovulatory menses than in equally hyperandrogenemic women with regular cycles.7, 37 These observations raise the possibility of a causal relationship between hyperinsulinemia and insulin resistance and anovulation. The finding that diet-induced weight loss accompanied by a reduction in fasting and glucose-stimulated plasma insulin levels in obese women with PCOS is associated with the resumption of ovulatory cycles lends further support to this hypothesis.25, 34 Hyperinsulinemia is also likely to have a significant effect on androgen production by the ovary. In many studies, a positive correlation has been noted between plasma insulin concentrations and those of testosterone and androstenedione.21 Obese women with PCOS are more likely to be hirsute than are their lean counterparts,24 and there is a close correlation between fasting insulin levels and free testosterone concentrations in these subjects.21 Weight reduction leads to parallel changes in insulin and free testosterone levels.25, 34 These clinical data suggest that insulin action may have an important role in the function of the ovary. This article reviews the data regarding the effects of insulin on the human ovary, both normal and polycystic. Evidence is presented to show that the polycystic ovary is not resistant to the action of insulin (at least in terms of steroidogenesis by granulosa cells) and that insulin exerts its effects by way of its own receptor and not by “cross-activation” of the type I receptor for insulin-like growth factors (IGFs). A central role is proposed for hyperinsulinemia in the mechanism of anovulation in PCOS.