Polycystic ovary syndrome (PCOS) is a heterogeneous disorder in which chronic anovulation is a common feature despite the presence of multiple micro- structures in the ovaries. A growing body of evidence has suggested that serum hyperinsulinemia contributes to the excess ovarian androgen secretion observed in women with PCOS. The standard therapy for anovulatory women with PCOS is oral administration of clomiphene citrate (CC). However, a significant proportion of women with PCOS fail to ovulate with the use of standard dosage of CC and are called CC-resistant PCOS. The recent introduction of the insulin-sensitizing agents as adjuvants to clomiphene citrate and gonadotropins has changed the treatment strategy. This is a comprehensive review of the literature, with an emphasis on the role of hyperinsulinemia in the pathogenesis of PCOS and on randomized controlled trials of the medical and surgical treatment options for women with CC-resistant PCOS. Although both standard and novel treatments were addressed in the present review, special attention was paid to the evidence in support of the recent introduction of insulin-sensitizing agents in the management of anovulatory woman with CC-resistant PCOS.
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