The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome.
OBJECTIVE
To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS).


METHODS
Twenty-four women with PCOS were evaluated before and after treatment (27+/-4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used.


RESULTS
In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3 beta-hydroxysteroid dehydrogenase in C(21) steroids (P<0.05) and in 17 beta-hydroxysteroid dehydrogenase (P<0.01) was observed, as was an increase in the activity of C17,20-lyase in the Delta(4) pathway (P<0.01). A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P<0.05) was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone (P<0.05), index of free testosterone (P<0.01), LH (P<0.05) and oestradiol (P<0.01), and an increase in the levels of 17-hydroxypregnenolone (P<0.05) were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3 beta-hydroxysteroid dehydrogenase in C21 steroids (P<0.01), in C17,20-lyase in the Delta 5 pathway (P<0.01), in 17 beta-hydroxysteroid dehydrogenase (P<0.05) and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for beta cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed (P<0.01).


CONCLUSIONS
Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.
Vrbíková
J
J
Institute of Endocrinology, Prague, Czech Republic. jvrbikova@endo.cz
Hill
M
M
Stárka
L
L
Cibula
D
D
Bendlová
B
B
Vondra
K
K
Sulcová
J
J
Snajderová
M
M
D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone; D000328:Adult; D005260:Female; D005951:Glucose Tolerance Test; D007987:Gonadotropin-Releasing Hormone; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008687:Metformin / Q000627:therapeutic use*; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*
D007004:Hypoglycemic Agents; D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D008687:Metformin