Metformin has direct effects on human ovarian steroidogenesis.
OBJECTIVE
To investigate the possibility of direct effects of metformin on ovarian steroidogenesis.


METHODS
Cultured ovarian cells.


METHODS
Academic research environment.


METHODS
Women undergoing bilateral salpingoophorectomy for benign gynecological disease.


METHODS
Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium.


RESULTS
The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude.


CONCLUSIONS
These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).
Mansfield
Rebecca
R
St. George's Hospital Medical School, Tooting, London, United Kingdom.
Galea
Ray
R
Brincat
Mark
M
Hole
David
D
Mason
Helen
H
D000328:Adult; D000735:Androstenedione / Q000096:biosynthesis*; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism
D007004:Hypoglycemic Agents; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D008687:Metformin