Metformin influence on hormone levels at birth, in PCOS mothers and their newborns.
BACKGROUND
Polycystic ovary syndrome (PCOS) tends to run in families and excess intrauterine androgen exposure has been suggested as one possible cause of PCOS. We wanted to study the relationship between maternal and offspring sex hormone levels and the possible effects of metformin treatment in PCOS pregnancies.


METHODS
We performed a post hoc analysis of a trial in which 40 pregnant women with PCOS were randomized in the first trimester, to use either metformin 850 mg twice daily or placebo until delivery. Maternal venous blood and umbilical arterial and venous blood samples were collected at delivery. Outcome measures were levels of androgens, estrogens and sex hormone binding globulin (SHBG).


RESULTS
(i) In newborns, SHBG levels were higher in the metformin group. All other hormones, both in mothers and offspring, were unaffected by metformin treatment. (ii) Mothers, who gave birth to boys, had higher estrone and estradiol levels compared with those who gave birth to girls. (iii) Male newborns had higher levels of testosterone, androstanediol glucuronide and estradiol compared with females. (iv) Positive correlations were found between maternal and newborn levels of androstenedione, dihydrotestosterone and estradiol.


CONCLUSIONS
Intrauterine metformin exposure seems to result in elevated SHBG levels in newborns. However, at birth, maternal and newborn androgen and estrogen levels are unaffected by metformin use in pregnancy. Although androgen and estrogen levels are higher in male newborns compared with females, maternal and newborn androgen and estrogen levels are highly correlated at birth.
Carlsen
S M
SM
Unit of Applied Clinical Research, Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway. sven.carlsen@ntnu.no
Vanky
E
E
D000328:Adult; D000728:Androgens / Q000097:blood; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000097:blood; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy; D011247:Pregnancy; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000728:Androgens; D007004:Hypoglycemic Agents; D012738:Sex Hormone-Binding Globulin; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D008687:Metformin