• Karen Elkind-Hirsch, Ory Marrioneaux, Madhu Bhushan, Denise Vernor, and Rajat Bhushan.
• Woman's Health Research Institute, 9050 Airline Highway, Baton Rouge, LA 70815, USA. Karen.Elkind-Hirsch@womans.org
• J. Clin. Endocrinol. Metab. 2008 Jul 1; 93 (7): 2670-8.

ContextInsulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Weight loss and use of insulin-lowering drugs have been shown to improve both reproductive and metabolic aspects of PCOS.ObjectiveWe evaluated exenatide (EX) and metformin (MET), alone and in combination (COM), on menstrual cyclicity, hormonal parameters, metabolic profiles, and inflammatory markers in overweight, insulin-resistant women with PCOS.Design, Setting, And ParticipantsSixty overweight oligoovulatory women with PCOS (body mass index > 27; 18-40 yr) were randomized to one of three treatment groups: MET [1000 mg twice daily (BID)], EX (10 microg BID), or COM (MET 1000 mg BID, EX 10 microg BID) for 24 wk. The primary outcome was menstrual frequency; secondary outcome measures included changes in ovulation rate, insulin action, anthropometric measures, androgen levels, and inflammatory markers.ResultsForty-two (70%) patients completed the study. COM therapy was superior to EX or MET monotherapy in improving menstrual cyclicity, ovulation rate, free androgen index, and insulin sensitivity measures and reducing weight and abdominal fat. Both EX arms were more effective in promoting weight loss than MET (P = 0.003).ConclusionsCOM appears better than either EX or MET alone on menstrual cycle frequency and hormonal and metabolic derangements. A marked decrease in central adiposity could partly explain the improvements in reproductive function, insulin-glucose parameters, and adiponectin observed in these overweight women with PCOS treated with COM therapy. Larger trials of longer duration are warranted to assess the long-term efficacy and safety of combined EX-MET therapy in overweight women with PCOS.

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