Sustained Maternal Hyperandrogenism During PCOS Pregnancy Reduced by Metformin in Non-obese Women Carrying a Male Fetus

Abstract

Context Large, longitudinal studies on androgen levels in pregnant women with polycystic ovary syndrome (PCOS) are lacking. While metformin has a mild androgen-lowering effect in non-pregnant women with PCOS, its effects on maternal androgen levels in pregnancy are less well understood.

Objective To describe androgen patterns in pregnant women with PCOS and in healthy control women, and to explore the potential effects of metformin on maternal androgen levels in PCOS.

Design and Setting A post hoc analysis from a randomized, placebo-controlled, multicenter study carried out at 11 secondary care centers and a longitudinal single-center study on healthy pregnant women in Norway.

Participants A total of 262 women with PCOS and 119 controls.

Intervention The participants with PCOS were randomly assigned to metformin (2 g daily) or placebo, from first trimester to delivery.

Main Outcome Measures Androstenedione (A4), testosterone (T), sex-hormone binding globulin (SHBG), and free testosterone index (FTI) at 4 time points in pregnancy.

Results Women with PCOS versus healthy controls had higher A4, T, and FTI, and lower SHBG at all measured time points in pregnancy. In the overall cohort of women with PCOS, metformin had no effect on A4, T, SHBG, and FTI. In subgroup analyses, metformin reduced A4 (P = 0.019) in nonobese women. Metformin also reduced A4 (P = 0.036), T (P = 0.023), and SHBG (P = 0.010) levels through pregnancy in mothers with a male fetus.

Conclusion Metformin had no effect on maternal androgens in PCOS pregnancies. In subgroup analyses, a modest androgen-lowering effect was observed in nonobese women with PCOS. In PCOS women carrying a male fetus, metformin exhibited an androgen-lowering effect.