The treatment of insulin resistance does not improve adrenal cytochrome P450c17alpha 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 P450c17alpha enzyme in patients with PCOS.


METHODS
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 (free 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 P450c17alpha enzyme and insulin resistance. It seems that there is no direct relationship between insulin resistance and adrenal P450c17alpha enzyme dysregulation.
Unlühizarci
K
K
Department of Endocrinology, Erciyes University School of Medicine, Kayseri, Turkey.
Keleştimur
F
F
Sahin
Y
Y
Bayram
F
F
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000735:Androstenedione / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D007527:Isoenzymes / Q000378:metabolism*; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007527:Isoenzymes; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D008687:Metformin