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. 2024 Mar 22:15:1364157.
doi: 10.3389/fendo.2024.1364157. eCollection 2024.

Thyroid function and polycystic ovary syndrome: a Mendelian randomization study

Zhendan Zhao  1 , Yuehua Gao  1 , Xiaoqing Pei  1 , Wenhao Wang  1 , Ruixian Wang  1 , Huawei Zhang  1
Affiliations

Thyroid function and polycystic ovary syndrome: a Mendelian randomization study

Zhendan Zhao et al. Front Endocrinol (Lausanne). .

Abstract

Background: Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted.

Methods: Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses.

Results: The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS.

Conclusions: Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.

Keywords: Mendelian randomization; free thyroxine; hyperthyroidism; hypothyroidism; polycystic ovary syndrome; thyroid-stimulating hormone.

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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.

Figures

Figure 1
Figure 1
Flow chart of overall design in the present study.
Figure 2
Figure 2
MR analysis for the causal effect of thyroid function on PCOS. IVW, inverse variance weighted; SNP, single-nucleotide polymorphism; OR, odds ratio; CI, confidence interval; PCOS, polycystic ovary syndrome; TSH, thyroid-stimulating hormone; FT4, free thyroxine.
Figure 3
Figure 3
MR analyses for the causal effect of PCOS on thyroid function. (A): Casual analyses of PCOS to FT4 and TSH. (B): Casual analyses of PCOS to hypothyroidism and hyperthyroidism. IVW, inverse variance weighted; SNP, single-nucleotide polymorphism; OR, odds ratio; CI, confidence interval; PCOS, polycystic ovary syndrome; TSH, thyroid-stimulating hormone; FT4, free thyroxine.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Shandong province nature funded projects (NO: ZR2023QH508 and ZR2023MH002).