Bidirectional causality between female reproductive traits and temporomandibular disorders

Temporomandibular disorders (TMD) are common, particularly in females of reproductive age, but it remains unclear if TMD and female reproductive traits directly influence each other. Previous studies have suggested links between reproductive factors, such as the menstrual cycle and menopause, and TMD, yet any causal link is unconfirmed. This study seeks to delineate the reciprocal causal interplay between female reproductive traits and TMD.

A bidirectional Mendelian randomization (MR) approach was applied to assess five reproductive traits-age at menarche, first sexual intercourse, first birth, last birth, and menopause-considering TMD as the outcome in one analysis and the exposure in the reverse. Statistical methods, including the inverse variance-weighted method, MR Egger, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), Cochran's Q test, and leave-one-out analyses, were used to examine pleiotropy and heterogeneity.

Later age at first sexual intercourse (odds ratio (OR) = 0.51, 95% confidence intervals (CI) 0.37-0.71, p = 6.46 × 10^-5), first birth (OR = 0.86, 95% CI 0.78-0.95, p = 0.003), and last birth (OR = 0.37, 95% CI 0.17-0.78, p = 0.009) were identified to be protective against TMD. No significant associations emerged for age at menarche or menopause. However, TMD onset may contribute to delayed menarche (Beta = 0.04, 95% CI 0.01-0.06, p = 0.035) without affecting other reproductive traits.

Genetically determined later timing of first sexual intercourse, first birth, and last birth may protect against TMD, while TMD onset may delay menarche, suggesting a bidirectional relationship between reproductive timing and TMD.