Conclusions: stating that weight reduction is the most effective way of addressing the underlying metabolic issueassociated with PCOS
http://www.bmj.com/cgi/content/full/317/7154/329 This is from a BMJ article
Good evidence supports the hypothesis that decreased peripheral insulin sensitivity and consequent hyperinsulinaemia are pivotal in the pathogenesis of polycystic ovarian syndrome.5 Peripheral insulin resistance is most evident in overweight patients: obesity and polycystic ovarian syndrome each seem to have a separate and synergistic relation with insulin resistance.5 The exact mechanism(s) for insulin resistance is uncertain, but a post-receptor defect in adipose tissue has been identified.5 Despite insulin resistance in adipose and skeletal muscle, the ovary remains relatively sensitive to insulin, and both insulin and insulin-like growth factor 1 have stimulatory effects on thecal androgen production.9 In fact, some lean women with polycystic ovarian syndrome, who may not have insulin resistance and therefore hyperinsulinaemia, may show enhanced ovarian sensitivity to insulin. Figure 1 shows how the relative excess of insulin or enhanced ovarian sensitivity to insulin, in combination with an elevated luteinising hormone concentration, brings about thecal hyperplasia, increased androgen secretion, arrest of follicular development, and therefore anovulation along with menstrual disturbance.
Insulin also acts on the liver to inhibit the production of sex hormone binding globulin and insulin-like growth factor 1 binding protein. A reduction in sex hormone binding globulin leads to an increase in the biologically available free testosterone. Thus, insulin resistance not only increases secretion of ovarian androgens but also promotes an increase in the proportion of free (active) hormone. Similarly, inhibition of production of insulin-like growth factor 1 binding protein results in an increased concentration of circulating free insulin-like growth factor 1, further enhancing ovarian androgen production.10
Current consensus suggests that the ovary is the principal site of excess androgen production, but some women with polycystic ovarian syndrome may have an adrenal contribution to the increased androgen production. The mechanisms for this remain obscure and are almost certainly multifactorial.
Insulin resistance
As the principal underlying defect in polycystic ovarian syndrome seems to be insulin resistance, the most appropriate treatment for all clinical presentations may be one that specifically addresses this problem.
Weight reduction has multiple benefits for obese women with polycystic ovarian syndrome.24 The resultant reduction in insulin resistance corrects the hormonal imbalance, promotes ovulation and regular menses, and improves the metabolic consequences of the disorder. Weight loss should therefore be encouraged, but it seems to be hard to achieve for this group of patients.
Insulin sensitising agents ---Recent trials have investigated the effect of such agents on polycystic ovarian syndrome. 16 17 24-33 Metformin, a biguanide often used in non-insulin dependent diabetes, has been the most commonly used. Troglitazone, a thiazolidinedione that improves muscle insulin sensitivity, has also been studied 17 27 but has recently been removed from the market because of adverse effects on hepatic function. Trials to date have included only small numbers of subjects, but results have been promising, with most showing reductions in concentrations of fasting serum insulin, androgen, and luteinising hormone. 16 17 26 28 29 31-33 In addition, circulating concentrations of sex hormone binding globulin increased, resulting in less bioactively available testosterone. Preliminary evidence indicates that treatment of obese women with polycystic ovarian syndrome with metformin restores regular menstrual cycles and ovulation. 26 30-32 Whether insulin sensitising agents can modify the vascular risk factors associated with the syndrome remains to be seen, but reductions in Lp (a) lipoprotein and plasminogen activator inhibitor 1 have been observed. 16 17 Additionally, some studies have reported that treated subjects have shown some weight loss despite continuation of their normal diet and lifestyle, 16 26 and others have demonstrated a reduction in central obesity. 26 29 33
Thus, treatments targeting the key factor in the disorder may not only resolve the gynaecological problems with which the syndrome presents, but also reduce the risk of vascular disease in later life. There is now an urgent need for randomised, placebo controlled trials to assess the potential benefits of these treatments for women's health.
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