Thyroid Status During Pregnancy in Women With Polycystic Ovary Syndrome and the Effect of Metformin

Anastasia Trouva, Michael Alvarsson, Jan Calissendorff, Bjørn Olav Åsvold, Eszter Vanky, Angelica Lindén Hirschberg, Anastasia Trouva, Michael Alvarsson, Jan Calissendorff, Bjørn Olav Åsvold, Eszter Vanky, Angelica Lindén Hirschberg

Abstract

Objective: Polycystic ovary syndrome (PCOS) and hypothyroidism are related conditions, and both are associated with adverse pregnancy outcomes. Knowledge is lacking about the complex interaction between thyroid status and PCOS during pregnancy. We investigated the thyroid status and its association with pregnancy complications in PCOS, and in relation to metformin treatment.

Design: Post-hoc analyses of two randomized, double-blind, placebo-controlled trials.

Methods: 288 pregnant women with PCOS were randomized to treatment with metformin or placebo from first trimester to delivery. We measured serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) at gestational week (gw) 5-12, 19, 32 and 36 and related to metformin treatment and pregnancy complications. Thyroid peroxidase antibodies (TPO-ab) were analyzed at inclusion and at gw 36.

Results: The overall prevalence of subclinical and overt hypothyroidism was 1.5% and 0%, respectively. The TSH level was not affected by metformin, whereas fT4 was significantly higher in the metformin group with less decrease throughout pregnancy compared to placebo, p<0.001. A lower decrease in fT4 during pregnancy correlated to less weight gain (r= -0.17, p=0.020) and tended to be associated with reduced odds ratio for gestational diabetes (OR 0.85 per 1 pmol/L, 95% CI 0.71;1.02).

Conclusions: In women with PCOS, metformin treatment during pregnancy was associated with less decrease in fT4 compared to placebo, while it did not affect TSH. A smaller decrease in fT4 correlated to less weight gain and tended to be associated with a lower risk of gestational diabetes.

Clinical trial registration: ClinicalTrials.gov, identifier NCT00159536 (The PregMet study); identifier NCT03259919 (The pilot study).

Keywords: PCOS (polycystic ovarian syndrome); hypothyroidism; metformin; pregnancy; pregnancy outcome.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Trouva, Alvarsson, Calissendorff, Åsvold, Vanky and Hirschberg.

Figures

Figure 1
Figure 1
Flowchart of the study design.
Figure 2
Figure 2
Thyroid status of all participants at inclusion in 1st trimester. Continuous lines represent the first trimester reference range recommended by ATA 2017 for TSH and reference limits for non-pregnant individuals for fT4.
Figure 3
Figure 3
Serum levels of TSH (mIU/L) at baseline, gestational week 19, 32 and 36 in the metformin and placebo groups presented as medians and 25th-75th percentiles.
Figure 4
Figure 4
Serum levels of fT4 (pmol/L) at baseline, gestational week 19, 32 and 36 in the metformin and placebo groups presented as geometric means and their 95% confidence intervals. **p

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