Insulin resistance in polycystic ovary syndrome

Abstract

Abstract The polycystic ovary syndrome, described first as the association of bilateral polycystic ovaries and amenorrhoea, oligomenorrhoea, hirsutism and obesity, was later shown to be a complex metabolic syndrome. The first purpose of this study was to investigate the occurrence of hyperinsulinaemia and the severity of insulin resistance and glucose tolerance disorders in polycystic ovary syndrome by means of the oral glucose tolerance test and the euglycaemic hyperinsulinaemic clamp. The next goal was to investigate whether women with polycystic ovary syndrome would benefit from insulin-sensitising drugs, and in particular to compare the effects of metformin and a contraceptive pill containing ethinyl oestradiol and cyproterone acetate. Altogether, 81 women with polycystic ovary syndrome and 34 healthy control subjects were involved in the study. Marked impairment of insulin sensitivity in obese subjects with polycystic ovary syndrome, including a decrease of both cellular oxidative and non-oxidative utilisation of glucose, and a slight non-significant decrease of insulin sensitivity in non-obese subjects was observed. Both non-obese and obese subjects with polycystic ovary syndrome exhibited increased abdominal obesity compared with the controls, confirming the fact that obesity, in particular abdominal obesity, is an important contributor in the development of insulin resistance in this syndrome. Metformin alleviated hyperandrogenism by essentially decreasing ovarian, but not adrenal androgen secretion. The improvement of hyperandrogenism and ovarian function seemed to be mediated by the improvement of hyperinsulinaemia, which resulted itself from subtle improvements in both hepatic insulin extraction and insulin sensitivity. Metformin decreased abdominal obesity and the release of free fatty acids from adipose tissue, and improved ovarian cyclicity and fertility. The transient decrease in serum leptin levels observed may have some role in the improvement of ovarian function. The contraceptive pill significantly improved hyperandrogenism and hirsutism, and it slightly affected glucose metabolism. Thus, it could be the treatment of choice in women with hirsutism problems and no fertility hopes. Metformin could be the drug of choice for women with polycystic ovary syndrome who wish to conceive. Because of its beneficial metabolic effects, the value of metformin in reducing the risk of cardiovascular diseases in polycystic ovary syndrome needs to be further studied