Metabolic and ovarian effects of rosiglitazone treatment for 12 weeks in insulin-resistant women with polycystic ovary syndrome

• Published in: Human reproduction (Oxford) 2006-01, Vol.21 (1), p.109-120
• Main Authors: Cataldo, Nicholas A., Abbasi, Fahim, McLaughlin, Tracey L., Basina, Marina, Fechner, Patricia Y., Giudice, Linda C., Reaven, Gerald M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Glucose - drug effects; Female; Gynecology. Andrology. Obstetrics; Hemorrhage - chemically induced; Humans; hyperandrogenism; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin Resistance; Luteinizing Hormone - blood; Medical sciences; Menstruation; Ovary - drug effects; ovulation; Ovulation - drug effects; polycystic ovary syndrome; Polycystic Ovary Syndrome - drug therapy; rosiglitazone; Sex Hormone-Binding Globulin - analysis; Testosterone - blood; Thiazolidinediones - administration & dosage; Thiazolidinediones - adverse effects; Thiazolidinediones - therapeutic use; Vagina - pathology
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dei289

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.