Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosiglitazone and clomiphene citrate therapy

OBJECTIVE: To investigate the effects of combined rosiglitazone and clomiphene citrate versus clomiphene citrate monotherapy on serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in polycystic ovary syndrome (PCOS) and to evaluate these therapeutic interventions in the link between hyperinsulinemia and hormonal perturbations in PCOS. METHODS: We performed a randomized clinical study at the King Abul-Aziz and Cairo University Hospitals. We studied 50 women with PCOS. Clinical diagnosis was based on hyperandrogenism; hyperinsulinism; oligomenorrhea; or amenorrhea, anovulatory cycles, and ultrasonographic findings. They were randomly assigned to two groups of 25 women each. One group was treated with rosiglitazone and clomiphene citrate; the other was treated only with clomiphene citrate. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, dehydroepiandrosterone sulfate (DHEAS), free testosterone, IGF-1, and IFGBP-3 were measured by specific radioimmunoassays before and after treatment. RESULTS: Combined rosiglitazone and clomiphene treatment led to a significant reduction in area under the insulin curve (AUC insulin), whereas clomiphene monotherapy did not lead to this reduction. Both types of treatment induced a significant decrease in LH, LH:FSH ratio, free testosterone, and IGF1:IGBP-3 ratio and were associated with a significant increase in IGFBP-3 levels. These changes were more pronounced in PCOS patients treated with combined rosiglitazone and clomiphene than in those treated with clomiphene monotherapy. Regular menstrual cycles occurred in 72% of the former group and 48% of the latter. CONCLUSION: Combined rosiglitazone and clomiphene was an effective therapeutic regimen for correcting insulin resistance in patients with PCOS, possibly by reducing IGF1 bioavailability to the ovaries, thus modifying the hyperandrogenic intrafollicular milieu that occurs in PCOS. In addition, the clinical and hormonal responses were better than with clomiphene alone.