The treatment of insulin resistance does not improve adrenal cytochrome P450c17 alpha 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 r esistance and hyperinsulinemia while body weight is maintained. Also we aim ed to see whether the reduction in insulin levels attenuates the activity o f adrenal P450c17 alpha enzyme in patients with PCOS. Design: We investigated the 17-hydroxyprogesterone (17-OHP) and androstened ione responses to ACTH, insulin responses to an oral glucose tolerance test (OGTT) and glucose disposal rate in an insulin tolerance test before and a fter metformin therapy (500 mg, orally, twice daily: for 12 weeks), Methods: The presence of hyperinsulinemia in 15 women with PCOS was demonst rated 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 response s 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 v s 7.9 +/- 0.6 nmol/l: androstenedione 11.8 +/- 0.8 vs 8.2 +/- 0.6 nmol/l) a nd 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. Metform in therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels. But 17-OHP and androstenedi one 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 relat ionship between insulin resistance and adrenal P450c17 alpha enzyme dysregu lation.