Rosiglitazone is a member of the thiazolidinedione group of drugs that have, along with metformin, been used to treat insulin resistance in women with polycystic ovary syndrome (PCOS). Unlike metformin, rosiglitazone is a true insulin sensitizer that affects the transcription of various genes having roles in carbohydrate and lipid homeostasis. It significantly lowers plasma glucose levels in diabetic individuals. This double-blind, placebo-controlled study enrolled 30 overweight women with PCOS whose body mass index exceeded 25 kg/m2 and whose average age was 29 years. All had symptoms of PCOS and were confirmed by vaginal ultrasonography as having polycystic ovaries. Participants were randomized to receive either rosiglitazone (ROSI) or placebo (PLA), the former in a dose of 4 mg once a day for 2 weeks followed by 4 mg twice daily for 4 months.
The 2 groups were clinically and endocrinologically comparable at the outset. Menstrual cycles had become more regular after 4 months of active treatment. There were no changes in the waist-to-hip ratio or in hirsutism scores. Serum levels of sex hormone-binding globulin increased in the treatment group. At the same time, levels of androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate all decreased. On oral glucose tolerance testing, tolerance improved in the ROSI group and the peripheral insulin response decreased. M values, reflecting insulin sensitivity, improved in the ROSI group from 33 to 40 μmol/kg/min. Serum levels of testosterone and follicle-stimulating hormone did not change in either the ROSI or the PLA group. Fasting serum free fatty acid levels decreased significantly in women treated with ROSI.
Treatment over 4 months with rosiglitazone significantly improved insulin resistance and menstrual cyclicity and, to some extent, hyperandrogenism in these overweight women with PCOS. This drug offers an effective and well-tolerated alternative for anovulatory women with PCOS who do not want to become pregnant.
Departments of Obstetrics and Gynaecology and Clinical Chemistry, Oulu University Hospital, Oulu, Finland
Hum Reprod 2006;21:1400–1407