Physical activity associated with age at menopause: A Mendelian randomization study

Area of Science:

• Reproductive Endocrinology
• Genetics
• Epidemiology

Background:

• Observational studies suggest physical activity influences age at menopause (ANM), but causal links are unclear.
• Understanding the relationship between lifestyle factors and ANM is crucial for women's health.
• Potential mediating factors like BMI, insomnia, hypertension, and hyperglycemia require investigation.

Purpose of the Study:

• To investigate the causal relationship between physical activity and age at menopause (ANM) using Mendelian randomization (MR).
• To identify potential mediating factors, including BMI, insomnia, hypertension, and hyperglycemia, in the physical activity-ANM relationship.
• To provide evidence-based recommendations for maintaining women's reproductive health.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis to assess the causal effect of physical activity on ANM.
• Two-step MR analysis to evaluate the mediating roles of BMI, insomnia, hypertension, and hyperglycemia.
• Utilized Inverse Variance Weighted (IVW) and other MR methods with sensitivity analyses for result robustness.

Main Results:

• Moderate physical activity was causally associated with a delayed age at menopause (β = 0.64, P = 0.04).
• No significant causal relationship was found between vigorous physical activity and ANM (P = 0.68).
• Body mass index (BMI) significantly mediated the effect of physical activity on delaying ANM (proportion mediated = 4.9%, P = 0.02).

Conclusions:

• Moderate physical activity is a protective factor, delaying the age at menopause.
• Body mass index (BMI) acts as a significant mediator in this relationship.
• Findings support lifestyle interventions for preventing premature ovarian failure and promoting reproductive health.