The treatment of insulin resistance does not improve adrenal cytochrome P450c17α enzyme dysregulation in polycystic ovary syndrome

Objective: To determine whether metformin, when given to non-diabetic women with polycystic ovary syndrome (PCOS), results in a reduction of insulin resistance and hyperinsulinemia while body weight is maintained. Also we aimed to see whether the reduction in insulin levels attenuates the activity of adrenal P450c17 alpha enzyme in patients with PCOS. Design: We investigated the 17-hydroxyprogesterone (17-OHP) and androstenedione responses to ACTH, insulin responses to an oral glucose tolerance test (OGTT) and glucose disposal rate in an insulin tolerance test before and after metformin therapy (500 mg, orally, twice daily: for 12 weeks), Methods: The presence of hyperinsulinemia in 15 women with PCOS was demonstrated by an OGTT and results were compared with those of 10 healthy women. Insulin sensitivity was measured by the rate of endogenous glucose disposal after i.v. bolus injection of insulin. 17-OHP and androstenedione responses to ACTH were measured in all the women with PCOS and the normal women. Results: Women with PCOS were hyperinsulinemic (102.0 +/- 13.0 (S.E.M.) VS 46.2 +/- 4.4 pmol/l) and hyperandrogenemic (Gee testosterone 15.3 +/- 1.7 vs 7.9 +/- 0.6 nmol/l: androstenedione 11.8 +/- 0.8 vs 8.2 +/- 0.6 nmol/l) and more hirsute (modified Ferriman-Gallwey score, 17.7 +/- 1.6 vs 3.0 +/- 0.3) than healthy women. in addition, women with PCOS had higher 17-OHP and androstenedione responses to ACTH when compared with healthy women. Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels. But 17-OHP and androstenedione responses to ACTH were unaltered in response to metformin. Conclusions: PCOS is characterized by hyperactivity of the adrenal P450c17 alpha enzyme and insulin resistance. It seems that there is no direct relationship between insulin resistance and adrenal P450c17 alpha enzyme dysregulation.