Endocrine Abstracts

Hyperinsulinaemia and insulin resistance (IR) are well recognised features of polycystic ovary syndrome (PCOS). There is an interaction of BMI with ovarian morphology so that the more obese the subject with PCOS the greater the degree of IR compared with weight-matched controls. There is an associated dyslipidaemia and it has been suggested that women with PCOS are at increased risk of cardiovascular disease, although there is, as yet, little direct evidence for this. It is, however, quite clear that women with PCOS are at increased risk of developing type 2 diabetes (T2D). Between 10-30% of obese young women with the 'classic' syndrome (ie hyperandrogenism and anovulation) have impaired glucose tolerance and it is estimated that women with PCOS are 3-6 times more likely than weight-matched controls to develop T2D in later life. Hyperinsulinaemia has also been implicated in the mechanism of anovulation in PCOS. Insulin appears to enhance the action of LH on granulosa cells, rendering small antral follicles prematurely responsive to LH. This may lead to inappropriately timed arrest of follicle growth. This putative action of insulin on granulosa cell mitosis and steroidogenesis, in the face of peripheral insulin resistance, lends weight to the hypothesis that there is differential, pathway-specific, insulin resistance in the ovary.

There is strong evidence for a major genetic component in the aetiology of PCOS and, not surprisingly, genes implicated in the pathogenesis of T2D and obesity have emerged as candidates in PCOS. These include the insulin gene regulatory region (INS-VNTR), Calpain-10, IRS-1 IRS-2 and PPAR gamma.

Treatment which reduces plasma insulin levels and IR has proved to be of benefit for both metabolic and reproductive reasons. Insulin sensitising drugs are likely to have an important role in management of these abnormalities but the simplest and most effective treatment is dietary.