PCOS The effects of rosiglitazone and metformin on menstrual cyclicity and hirsutism in polycystic ovary syndrome MURAT YILMAZ 1 , AYHAN KARAKOC ¸ 2 , FU ¨ SUN B. TO ¨ RU ¨ NER 2 , NURI C ¸ AKIR 2 , BU ¨ LENT TIRAS 3 , GO ¨ KSUN AYVAZ 2 , & METIN ARSLAN 2 1 Department of Endocrinology and Metabolism, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey, 2 Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Ankara, Turkey, and 3 Department of Obstetrics and Gynecology, Faculty of Medicine, Gazi University, Ankara, Turkey Abstract Objective. The aim of the present study was to assess the effects of metformin and rosiglitazone on menstrual cyclicity and hirsutism in patients with polycystic ovary syndrome (PCOS). Materials and methods. Ninety-six patients were included in the study. Serum sex steroids, serum fasting glucose and insulin levels, and insulin response to a 75-g oral glucose tolerance test were assessed in all patients. Menstrual cyclicity, with recording of menses in the 6-month periods before the study and during treatment, was evaluated in each patient. Patients were divided into two groups: one was treated with metformin (MET group, n ¼ 48), while the other received rosiglitazone (ROSI group, n ¼ 48). At baseline and after 24 weeks of treatment all patients underwent hormonal and clinical assessments, including body mass index (BMI), waist and hip measurements and Ferriman – Gallwey (FG) scores. Results. Of the 96 patients included in the study, 88 (91.7%) were able to complete it and yielded data for analyses. After the 24-week treatment period, fasting insulin levels and area under the curve for serum insulin decreased significantly, while the glucose/insulin ratio increased in both groups. The degree of reduction in serum free testosterone and androstenedione levels was similar in the two groups. The decreases in luteinizing hormone/follicle-stimulating hormone ratio and serum dehydroepiandrosterone sulfate levels were significantly greater in the ROSI group compared with the MET group. BMI increased in the ROSI group, while it decreased in the MET group. In patients with menstrual disturbance treated with rosiglitazone, menstrual cycles became regular in 87.8%, while improvement occurred in 79.3% of the patients treated with metformin. FG score decreased in both ROSI and MET groups, but the degree of decrease was significantly greater in the ROSI group than in the MET group. Conclusion. Our data show that both metformin and rosiglitazone improve ovarian function and hirsutism in patients with PCOS. Rosiglitazone appears better than metformin in the treatment of hirsutism and has better patient tolerance. Keywords: Polycystic ovary syndrome, menstrual cyclicity, hirsutism, metformin, rosiglitazone Introduction Polycystic ovary syndrome (PCOS) is the most common endocrine disorder seen in premenopausal women, affecting 5–10% of this population [1]. It is characterized by menstrual irregularities and bio- chemical and/or clinical signs of hyperandrogenism such as hirsutism, seborrhea and acne [2]. Addi- tionally, approximately half of all women with PCOS are overweight or obese. Independent of the presence of obesity though, these women are frequently insulin-resistant and therefore have hyperinsulinemia, which appears to play a patho- genic role in the disease [3,4]. Hyperinsulinemia is thought to result in increased androgen biosyn- thesis and decreased sex hormone-binding globulin (SHBG), which is known to play a major role in the pathogenesis of hyperandrogenism [4]. The use of oral antihyperglycemic drugs, predomi- nantly metformin and thiazolidenediones, has been shown to improve insulin sensitivity and ovarian func- tion of women with PCOS. The biguanide metformin inhibits hepatic glucose production and enhances peripheral tissue sensitivity to insulin, resulting in a decrease in insulin secretion [5]. In women with PCOS, many studies have demonstrated the efficacy of metformin in improving menstrual cycle pattern, ovulation and pregnancy outcomes [6–16]. Rosig- litazone, a peroxisome proliferator-activated receptor- g agonist, increases the uptake and utility of glucose in peripheral tissues and decreases hepatic gluconeogen- esis [17]. Most studies have shown that rosiglitazone Correspondence: M. Yilmaz, C ¸ ınar Sokak 77/4, Yenimahalle, Ankara, Turkey. Tel: 90 318 2252820. Fax: 90 318 2252819. E-mail: murartt@hotmail.com Gynecological Endocrinology, September 2005; 21(3): 154–160 ISSN 0951-3590 print/ISSN 1473-0766 online ª 2005 Taylor & Francis DOI: 10.1080/09513590500231627