Mendelian randomization study of thyroid function and anti-Müllerian hormone levels

Area of Science:

• Endocrinology
• Reproductive Biology
• Genetics

Background:

• Previous studies suggest an association between thyroid function and anti-Müllerian hormone (AMH), a marker of ovarian reserve, but causality remains unclear.
• Investigating the causal relationship between thyroid hormones and AMH is crucial for understanding reproductive health.
• This study addresses the uncertainty surrounding thyroid function's impact on ovarian reserve markers.

Approach:

• Utilized large-scale genetic summary statistics from multiple consortia for robust Mendelian randomization (MR) analyses.
• Employed two-sample MR to assess causality between thyrotropin (TSH), free thyroxine (fT4), hypothyroidism, and hyperthyroidism with AMH levels.
• Conducted sensitivity and subgroup analyses to ensure the reliability of the findings.

Key Points:

• MR analyses revealed no causal relationship between normal or full-range TSH, normal fT4, subclinical hypothyroidism, subclinical hyperthyroidism, or overt hypothyroidism and AMH levels.
• Subgroup analyses, including TSH in individuals under 50, also showed no causal association.
• Sensitivity analyses confirmed the robustness of most results, with a minor exception for fT4 in a specific genetic subgroup.

Conclusions:

• The study concludes that genetically predicted thyroid function is not causally associated with AMH levels in the European population.
• These findings clarify the relationship between thyroid health and ovarian reserve markers.
• No evidence supports a causal link, suggesting other factors may mediate the observed associations.