A randomized controlled trial of the efficacy of rosiglitazone and clomiphene citrate versus metformin and clomiphene citrate in women with clomiphene citrate-resistant polycystic ovary syndrome

Abstract

Objective: To compare the efficacy of rosiglitazone and clomiphene citrate (CC) with metformin and CC in women with CC-resistant polycystic ovary syndrome (PCOS).

Design: Randomized controlled trial (RCT).

Setting: A university teaching hospital in Jeddah, Saudi Arabia.

Patient(s): Twenty-five women with CC-resistant PCOS.

Intervention(s): Twelve women were assigned to the rosiglitazone and CC group, and 13 women were assigned to the metformin and CC group for three treatment cycles. The first cycle was started on the first day of the period with either rosiglitazone (4 mg twice daily) or metformin (500 mg three times daily) and continued for three cycles. Clomiphene citrate (100 mg) from the third day for 5 days was added to each cycle.

Main outcome measure(s): Ovulation rate, number of follicles and estradiol (E2) on day 12 of the cycle, pregnancy rate, and changes in fasting glucose, serum insulin, HbA(1C), total testosterone (T), free T, luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), delta4-androstenedione (delta4-A), sex hormone-binding globulin (SHBG), insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3.

Result(s): No significant differences were found in the baseline characteristics of both groups. Ovulation rate was significantly higher in the rosiglitazone and CC group (18 out of 28 cycles [[64.3%]]) than the metformin and CC group (12 out of 33 cycles [[36.4%]]) (P=.035). Similarly, statistically significant differences were found in the number of follicles > or =14 mm in the rosiglitazone and CC group (2.2 +/- 1) compared with the metformin and CC group (1.1 +/- 0.9) (P=.02) and E2 on day 12 of the cycle in the rosiglitazone and CC group (1,991 +/- 1,389 pmol/L) compared with the metformin and CC group (548 +/- 327) (P<.001). The pregnancy rate was also higher in the rosiglitazone and CC group (6 out of 12 [[50%]] women) than the metformin and CC group (5 out of 13 [[38.5%]] women), but did not reach statistical significance (P=.58). Both groups showed no significant changes in fasting plasma glucose or HbA(1C) or IGFBP-3 values. However, in both groups, fasting serum insulin, total T, free T, LH, DHEA-S, delta4A, and IGF-1 levels decreased significantly, and SHBG and IGFBP-1 exhibited significant increases.

Conclusion(s): These findings suggest that short-term use of rosiglitazone and CC is more efficacious than metformin and CC in ovulation induction in women with CC-resistant PCOS.