Effects of low-dose metformin in Japanese women with clomiphene-resistant polycystic ovary syndrome.

Abstract

Background and Aims: The aim of the present prospective observational study was to evaluate the effects of low-dose, short-term metformin, in combination with clomiphene (CC), in CC-resistant infertile Japanese women with polycystic ovary syndrome (PCOS). Methods: Metformin therapy was administered orally (one 250mg tablet, twice daily) to 15 CC-resistant infertile patients with PCOS, beginning on the third day of progestin-induced withdrawal bleeding, and was continued for 14days in the first cycle. In the event of anovulation, 100mg/day of CC was given during subsequent cycles on days 5-9, in addition to the aforementioned dose of metformin. Hormonal and metabolic parameters were measured on the second or third days of the first cycle and also the fourth cycle, following an overnight fast. Results: None of the 15 women successfully ovulated during the first cycle with metformin treatment alone. After two subsequent cycles with the combination of CC and metformin, ovulation was confirmed in 17 of 29 cycles (61%) and in 13 of 15 patients (87%). Two women became pregnant within 2months of therapy (13%). There were no cases of ovarian hyperstimulation syndrome. Following three cycles of metformin therapy, a slight reduction in serum levels of luteinizing hormone (LH), free testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin A1c and total cholesterol was seen, while serum LH/follicle-stimulating hormone ratio and serum level of low-density lipoprotein cholesterol were significantly decreased. Although there were no significant differences between the responder (n=11) and non-responder (n=2) groups at baseline, the levels of plasma fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the non-responder group compared with the responder group after three cycles. Conclusion: Low-dose, short-term metformin, combined with CC, can improve ovulation rates in CC-resistant infertile Japanese women with PCOS. (Reprod Med Biol 2004; 3: 19-26).