Insulin and hyperandrogenism in women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a very common endocrine disorder characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and/or polycystic ovaries. But most experts consider that hyperandrogenism is the main characteristic of PCOS. Several theories propose different mechanisms to explain PCOS manifestations: (1) a primary enzymatic default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in gonadotropin releasing hormone (GnRH) secretion that promotes luteal hormone (LH) secretion; or (3) alterations in insulin actions that lead to insulin resistance with compensatory hyperinsulinemia. However, in the past 20 years there has been growing evidence supporting that defects in insulin actions or in the insulin signalling pathways are central in the pathogenesis of the syndrome. Indeed, most women with PCOS are metabolically insulin resistant, in part due to genetic predisposition and in part secondary to obesity. But some women with typical PCOS do not display insulin resistance, which supports the hypothesis of a genetic predisposition specific to PCOS that would be revealed by the development of insulin resistance and compensatory hyperinsulinemia in most, but not all, women with PCOS. However, these hypotheses are not yet appropriately confirmed, and more research is still needed to unravel the true pathogenesis underlying this syndrome. The present review thus aims at discussing new concepts and findings regarding insulin actions in PCOS women and how it is related to hyperandrogenemia.

Predictors of Insulin Resistance and Metabolic Complications in Polycystic Ovarian Syndrome in an Eastern Indian Population

“…These are areas of unresolved understanding with regard to PCOS. Although, proposed mechanisms for insulin induced reproductive abnormalities include inappropriate ovarian steroidogenesis, excessive LH secretion and abnormalities in glucose uptake [18], in effect increased insulin does not appear to govern gonadotropin secretion directly. PCOS women treated with pioglitazone demonstrated improved insulin sensitivity without alterations in LH pulse frequency or amplitude, or gonadotropin responses to GnRH [37].…”

“…Although, it is widely accepted that hyperinsulinemia due to insulin resistance causes hyperandrogenism, studies undertaken with reverse aim showed that testosterone administration caused insulin resistance in skeletal muscle of female rats and in adipocytes of women in vitro [20]. On the other hand, the results of some studies suggested that these two conditions might be two separate entities [18]. The absence of significant association between hyperandrogenemia and insulin resistance in some recent studies have further supported this view [21].…”

“…The link between PCOS and hyperinsulinemia is further complicated by the observations that suggest direct relationship between insulin resistance and androgen levels. Studies demonstrated positive correlations between insulin and androgen levels [5,18] and such correlations existed in both obese and non-obese PCOS women [19]. Although, it is widely accepted that hyperinsulinemia due to insulin resistance causes hyperandrogenism, studies undertaken with reverse aim showed that testosterone administration caused insulin resistance in skeletal muscle of female rats and in adipocytes of women in vitro [20].…”

Hormonal alterations in PCOS and its influence on bone metabolism

“…SREBP-1 is a transcription factor responsible for the biosynthesis of various fatty acids (Shao & Espenshade 2012). Insulin regulates SREBP activation and translocation from cytoplasm into the nucleus through PI3K/Akt and mammalian target of rapamycin (mTOR) signaling pathway (Baptiste et al 2010).…”

“…It is due to a combination of genetic and environmental factors. A dysfunction of the hypothalamicpituitary-ovarian or adrenal axis was proposed to be the cause of hyperandrogenemia in women with PCOS (Hall et al 1998, Baptiste et al 2010. Risk factors for the…”