# Bidirectional causality between female reproductive traits and temporomandibular disorders

## TL;DR

This study finds a two-way link between female reproductive traits and temporomandibular disorders, suggesting that later events like first birth may reduce TMD risk, while TMD might delay menarche.

## Contribution

The study provides novel evidence of bidirectional causality between reproductive traits and TMD using Mendelian randomization.

## Key findings

- Later age at first sexual intercourse, first birth, and last birth are protective against TMD.
- TMD onset may delay menarche but does not affect other reproductive traits.
- No significant associations were found for age at menarche or menopause with TMD.

## Abstract

Background: 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. Methods: 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. Results: 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.
Conclusions: 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.