Li Wei Cho et al suggested to be cost-effective on the basis of computer pro- jected lifetime risk (Ratner 2006). In accord with that is the observation that signiﬁcant weight loss, ie, >15% of body weight, has been found to improve the metabolic proﬁle of PCOS women (Kiddy et al 1989). Insulin sensitizers Metformin Metformin is effective in the treatment of metabolic syn- drome and modestly increases menstrual regularity and ovulation, and may improve hirsutism in patients with PCOS (Harborne et al 2003). Metformin treatment in lean women with PCOS also improves insulin resistance and hyperan- drogenism without a change in BMI (Nestler and Jakubowicz 1997). Whilst metformin appears to induce cardio-protective effects on serum insulin (Sahin et al 2004), serum lipids (Ibanez et al 2004), and PAI-1 (Song et al 2002), the actual protection from long-term mortality and morbidity of car- diovascular disease has yet to be demonstrated. In addition, it has been suggested that metformin has a beneﬁcial effect on endothelial function in patients with polycystic ovarian syndrome (Orio et al 2005). Thiazolidinediones Pioglitazone and rosiglitazone have also shown positive cardiometabolic effects, reducing hyperandrogenemia, and hirsutism as well as regulating the menstrual cycle in women with PCOS (Brettenthaler et al 2004; Sepilian and Nagamani 2005; Cataldo et al 2006). Rosiglitazone was found to markedly reduce liver fat, increase insulin clearance, double adiponectin concentrations, and unlike metformin, it also increases peripheral insulin sensitivity (Tiikkainen et al 2004). However, thiazolidinediones causes weight gain that may not be a desireable effect in this population of young women whose initial presenting complaint may well be the inability to lose weight. Orlistat Orlistat, a pancreatic lipase inhibitor, limits the absorption of dietary fat. We have recently shown that it signiﬁcantly reduced body weight and that there was a reduction in total testosterone levels in PCOS women equal to that of metfor- min (Jayagopal et al 2005). In women with PCOS, weight loss is associated with an improvement in insulin sensitivity and a reduction of the insulin concentration in the plasma (Ajossa et al 2004). Therefore weight reduction with orlistat would be a suitable adjunct to insulin sensitizers in the treat- ment of patients with PCOS. 60 Sibutamine Sibutramine, a selective serotonin and adrenergic reuptake inhibitor, has shown positive effects on hyperandrogenemia, and clinical metabolic risk factors for cardiovascular disease in obese women with PCOS (Sabuncu et al 2003). However, sibutramine has to be prescribed with care in patients with hypertension, and in patients with PCOS, metformin may be a more effective treatment in the prompt restoration of ovarian function as compared with sibutramine (Lazurova et al 2004). In summary, cardiovascular disease studies in PCOS have been inconclusive, with some suggesting an increased in cardiac events among women with PCOS whilst others showed no difference. The mainstay of treatment is the encouragement of diet and exercise augmented by weight reducing medication and use of insulin sensitizers like metformin. Insulin sensitisers have beneﬁcial effects on menstrual regularity, but their use speciﬁcally for potential cardio-protection needs to be clariﬁed. References Ahima RS, Flier JS. 2000. Adipose tissue as an endocrine organ. Trends Endocrinol Metab, 11:327–32. Ajossa S, Guerriero S, Paoletti AM, et al. 2004. The treatment of polycystic ovary syndrome. Minerva Ginecol, 56:15–26. Alberti KG, Zimmet P, Shaw J. 2006. Metabolic syndrome--a new world- wide deﬁnition. A Consensus Statement from the International Diabetes Federation. Diabet Med, 23:469–80. Alberti KG, Zimmet PZ. 1998. 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