Hum. Reprod. Advance Access originally published online on September 9, 2005
Human Reproduction 2006 21(1):109-120; doi:10.1093/humrep/dei289
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Metabolic and ovarian effects of rosiglitazone treatment for 12 weeks in insulin-resistant women with polycystic ovary syndrome
1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Divisions of 2 Cardiovascular Medicine and 3 Endocrinology, Gerontology and Metabolism, Department of Medicine and 4 Division of Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
5 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Stanford University Medical Center, 300 Pasteur Drive, MC5317, Stanford, CA 94305-5317, USA. E-mail: nixie54{at}yahoo.com
BACKGROUND: Insulin sensitizers have favourable metabolic and ovarian effects in polycystic ovary syndrome (PCOS). This study examined rosiglitazone, a thiazolidinedione, in PCOS. METHODS: In a prospective, open-label study, the effects of rosiglitazone on metabolism and ovarian function were examined in 42 non-diabetic women with PCOS classified according to the National Institute of Child Health and Human Development criteria and insulin resistance (IR) by steady-state plasma glucose (SSPG) 
10 mmol/l on octreotide-modified insulin suppression testing. Participants were randomized to rosiglitazone 2, 4 or 8 mg daily for 12 weeks. Endpoints included ovulation and menstrual pattern; serum testosterone, sex hormone-binding globulin (SHBG), and LH; and changes in IR and glucose–insulin responses on 8 h mixed-meal profile. RESULTS: After rosiglitazone 8 mg daily for 12 weeks, SSPG declined and insulinaemia fell by 46%; lower doses gave lesser effects. Serum LH, total and free testosterone were unchanged; SHBG increased. With rosiglitazone, ovulation occurred in 23/42 women (55%), without significant dose dependence. Both before and during treatment, ovulators on rosiglitazone had lower circulating insulin and free testosterone and higher SHBG than non-ovulators. Testosterone declined only in a subgroup of ovulators with early vaginal bleeding after starting rosiglitazone. CONCLUSIONS: Rosiglitazone in insulin-resistant PCOS promoted ovulation and dose-dependently decreased IR and insulinaemia; ovulators had lower circulating insulin and testosterone.
Key words: hyperandrogenism/insulin resistance/ovulation/polycystic ovary syndrome/rosiglitazone
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