Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome.
Hyperinsulinemia contributes to the ovarian androgen overproduction and glucose intolerance of polycystic ovary syndrome (PCOS). We sought to determine whether metformin would reduce insulin levels in obese, nondiabetic women with PCOS during a period of weight maintenance and thus attenuate the ovarian steroidogenic response to the GnRH agonist leuprolide. All subjects (n = 14) had an oral glucose tolerance test, a GnRH agonist (leuprolide) test, a frequently sampled iv glucose tolerance 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/m2, posttreatment, 39.1 +/- 7.9 kg/m2), oral glucose tolerance, insulin sensitivity (Si; 0.87 +/- 0.82 vs. 0.74 +/- 0.63 x 10(-5) min-1/ pmol.L), and the relationship between Si and first phase insulin secretion (AIRg vs. Si) were not improved by metformin. The insulin secretory response to glucose, administered in both graded and oscillatory fashions, was likewise unaltered in response to metformin. Free testosterone levels remained about 2-fold elevated (pretreatment, 26.6 +/- 12.7 pg/mL; posttreatment, 22.4 +/- 9.8 pg/mL). Both basal and stimulated LH and FSH levels were unaffected by metformin. The mean responses to leuprolide of 17-hydroxyprogesterone (pretreatment, 387 +/- 158 ng/dL; posttreatment, 329 +/- 116 ng/dL) as well as those of the other ovarian secretory products (androstenedione, dehydroepiandrosterone, progesterone, and estradiol) were not attenuated by metformin. We conclude that hyperinsulinemia and androgen excess in obese nondiabetic women with PCOS are not improved by the administration of metformin.
Ehrmann
D A
DA
Department of Medicine, University of Chicago, Illinois 60637, USA. dehrmann@medicine.bsd.uchicago.edu
Cavaghan
M K
MK
Imperial
J
J
Sturis
J
J
Rosenfield
R L
RL
Polonsky
K S
KS
D000328:Adult; D000728:Androgens / Q000097:blood; D005260:Female; D005947:Glucose / Q000502:physiology; D005951:Glucose Tolerance Test; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D000078790:Insulin Secretion; D008687:Metformin / Q000627:therapeutic use*; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013256:Steroids / Q000096:biosynthesis*
D000728:Androgens; D006062:Gonadotropins; D007004:Hypoglycemic Agents; D007328:Insulin; D013256:Steroids; D008687:Metformin; D005947:Glucose