J. Vrbikova et al., The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome, EUR J ENDOC, 144(6), 2001, pp. 619-628
Objective: To evaluate adrenal and ovarian steroidogenesis before and after
long-term treatment with metformin in women with polycystic ovary syndrome
(PCOS).
Design and Methods: Twenty-four women with PCOS were evaluated before and a
fter treatment (27 +/- 4 weeks) with metformin (1000 mg/day) using adrenoco
rticotrophin (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 cyclici
ty was observed. No significant change in basal steroid levels was found. A
fter ACTH stimulation, a significant decrease in the activity of 3 beta -hy
droxysteroid dehydrogenase in C-21 steroids (P < 0.05) and in 17<beta>-hydr
oxysteroid 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 significa
nt growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P < 0.05
) was detected. With regard to ovarian steroidogenesis, a significant decre
ase in the stimulated levels of testosterone (P < 0.05), index of free test
osterone (P < 0.01), LH (P < 0.05) and oestradiol (P < 0.01), and an increa
se in the levels of 17-hydroxypregnenolone (P < 0.05) were detected. In the
indices of ovarian enzyme activities, we observed a significant decrease i
n 3<beta>-hydroxysteroid dehydrogenase in C-21 steroids (P < 0.01), in C17.
20-lyase in the 115 pathway (P < 0.01), in 17 beta -hydroxysteroid dehydrog
enase (P < 0.05) and in aromatase. In glucose metabolism, a tendency toward
s reduction in the homeostasis model assessment (HOMA)-R (for insulin resis
tance) 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 enzymati
c activities both in the ovary and the adrenal glands, without apparent cha
nges in basal steroid levels and in insulin sensitivity.