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Is thyroid function associated with polycystic ovary syndrome? A bidirectional Mendelian randomization study.

Qinnan Zhang1, Wencai Ke2, Jun Ye3

  • 1Department of Endocrinology, Fifth People's Hospital of Shanghai Fudan University, Shanghai, China.

Endocrine
|March 13, 2024
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Summary

This study explored the causal link between thyroid function and polycystic ovary syndrome (PCOS) using Mendelian randomization. While normal thyroid-stimulating hormone (TSH) showed a protective association, no definitive causal relationship was established after rigorous statistical correction.

Keywords:
Causal associationMendelian randomizationPolycystic ovary syndromeThyroid function

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Area of Science:

  • Endocrinology
  • Genetics
  • Reproductive Medicine

Background:

  • Observational studies suggest a link between thyroid function and polycystic ovary syndrome (PCOS).
  • The causal nature of this association requires further investigation.
  • Understanding this relationship is crucial for managing PCOS and thyroid disorders.

Purpose of the Study:

  • To investigate the underlying causal association between thyroid function status and PCOS.
  • To differentiate between observational associations and true causal links.
  • To utilize Mendelian randomization for robust genetic evidence.

Main Methods:

  • Bidirectional Mendelian randomization (MR) analysis was performed.
  • Utilized large-scale genome-wide association study (GWAS) data for thyroid function (TSH, FT4, hyperthyroidism, hypothyroidism) and PCOS.
  • Included primary analysis of 10,074 PCOS cases and 103,164 controls, with validation in independent cohorts.

Main Results:

  • A nominal association was observed between normal TSH levels and a reduced risk of PCOS (OR=0.78, P=0.029).
  • Meta-analysis suggested PCOS may contribute to hyperthyroidism (OR=1.37, P=0.012).
  • No statistically significant causal relationships were confirmed after Bonferroni correction.

Conclusions:

  • Mendelian randomization analysis did not establish a definitive genetic causal link between thyroid function and PCOS.
  • The potential protective role of normal TSH warrants further exploration.
  • Future research should examine subgroups based on age and BMI to clarify the complex relationship.