EFFECTS OF METFORMIN ON INSULIN-SECRETION, INSULIN ACTION, AND OVARIAN STEROIDOGENESIS IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME

Hyperinsulinemia contributes to the ovarian androgen overproduction an d glucose intolerance of polycystic ovary syndrome (PCOS). We sought t o determine whether metformin would reduce insulin levels in obese, no ndiabetic women with PCOS during a period of weight maintenance and th us attenuate the ovarian steroidogenic response to the GnRH agonist le uprolide. All subjects (n=14) had an oral glucose tolerance test, a Gn RH agonist (leuprolide) test, a frequently sampled iv glucose toleranc e test, graded and oscillatory glucose infusions, and a dual energy x- ray absorptiometry scan before and after treatment with metformin (850 mg, orally, three times daily for 12 weeks). With weight maintenance (body mass index: pretreatment, 39.0+/-7.7 kg/m(2); posttreatment, 39. 1+/-7.9 kg/m(2)), oral glucose tolerance,insulin sensitivity (Si; 0.87 +/-0.82 vs. 0.74+/-0.63x10(-5) min(-1)/pmol . L), and the relationship between Si and first phase insulin secretion (AIRg us. Si) were not i mproved by metformin. The insulin secretory response to glucose, admin istered in both graded and oscillatory fashions, was likewise unaltere d in response to metformin. Free testosterone levels remained about 8- fold elevated (pretreatment, 26.6+/-12.7 pg/mL; posttreatment, 22.4+/- 9.8 pg/mL). Both basal and stimulated LH and FSK levels were unaffecte d by metformin. The mean responses to leuprolide of 17-hydroxyprogeste rone (pretreatment, 387+/-158 ng/dL; posttreatment, 329+/-116 ng/dL) a s well as those of the other ovarian secretory products (androstenedio ne, dehydroepiandrosterone, progesterone, and estradiol) were not atte nuated by metformin. We conclude that hyperinsulinemia and androgen ex cess in obese nondiabetic women with PCOS are not improved by the admi nistration of metformin.