Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome.
OBJECTIVE
To determine whether the administration of metformin, an insulin-sensitizing agent, is followed by changes in adrenal steroidogenesis in women with polycystic ovary syndrome (PCOS).


METHODS
Prospective trial.


METHODS
Department of Obstetrics and Gynecology, University of Siena, Siena, Italy.


METHODS
Fourteen women with PCOS.


METHODS
Blood samples were obtained before (-15 and 0 minutes) and after (15, 30, 45, and 60 minutes) the administration of ACTH (250 microg). Metformin then was given at a dosage of 500 mg three times a day for 30-32 days, at which time the pretreatment study was repeated.


METHODS
The adrenal androgen responses to ACTH before and after treatment with metformin.


RESULTS
Ovulation occurred in two women (14%) in response to metformin treatment. A significant reduction in basal concentrations of free testosterone and a significant increase in concentrations of sex hormone-binding globulin were observed. The administration of metformin was associated with a significant reduction in the response of 17alpha-hydroxyprogesterone, testosterone, free testosterone, and androstenedione to ACTH. The ratio of 17alpha-hydroxyprogesterone to progesterone, which indicates 17alpha-hydroxylase activity, and the ratio of androstenedione to 17alpha-hydroxyprogesterone, which indicates 17,20-lyase activity, were significantly lower after a month of metformin treatment, indicating a reduction in the activities of these enzymes.


CONCLUSIONS
The administration of metformin to unselected women with PCOS led to a reduction in the adrenal steroidogenesis response to ACTH. This finding supports the hypothesis that high insulin levels associated with PCOS may cause an increase in plasma levels of adrenal androgens.
la Marca
A
A
Department of Obstetrics and Gynecology, University of Siena, Italy.
Morgante
G
G
Paglia
T
T
Ciotta
L
L
Cianci
A
A
De Leo
V
V
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone; D000328:Adult; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*
D000305:Adrenal Cortex Hormones; D007004:Hypoglycemic Agents; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D008687:Metformin