Endocrine Abstracts

Hyperandrogenism, hyperinsulinemia and insulin resistance are the cardinal features of most women with the polycystic ovary syndrome (PCOS). They contribute in different ways to its phenotypic expression, including hirsutism, menses abnormalities, oligo-anovulation, metabolic disturbances, and susceptibility to develop type 2 diabetes. From the theoretical point of view, individual pharmacotherapy of PCOS should be planned in order to counteract the main pathophysiological mechanisms, with the aim of producing an overall benefit on all clinical and biochemical aspects of the disorders, after the major complaints of each individual have been considered. Dietary-induced weight loss and life style modifications should however represent the first line therapeutic advice for every obese woman with PCOS. Whether this applies in otherwise normal weight PCOS women has not yet been demonstrated, although the scientific basis for such an approach is appealing, particularly in those with abdominal fatness and insulin resistance.

Since almost all obese PCOS women and more than half of lean PCOS women are insulin resistant, therefore presenting some degree of hyperinsulinemia, the use of insulin sensitizers should be suggested in most patients with PCOS. Their use has been associated with a reduction in androgen levels, improvement of insulin and insulin resistance, and reversal of serum lipid abnormalities and PAI-1. This therapy has also been associated with a decrease in hirsutism and acne, although the main benefit should be expected on menses abnormalities, anovulation and infertility. In our experience, at least one third of obese PCOS women improve menses and ovulation after a short period of treatment with metformin and life style changes. Antiandrogens have been used for a long-time in the treatment of hirsutism and hyperandrogenemia, We have recently performed pilot studies to investigate potential additional effects of long-term treatment with antiandrogens, and we have found that they can selectively improve visceral fatness, lipid abnormalities and even insulin resistance, although their main effect was on hirsutism and hyperandrogenemia.

The dual approach with insulin sensitizers and/or antiandrogens may provide a rationale for targeting different therapeutical options according to the required outcomes.