Abstract
Background: Dysmenorrhea is a common gynecological symptom among reproductive-aged women, associated with substantial pain and decreased quality of life. Previous studies have suggested that inflammatory and hormonal fluctuations linked to dysmenorrhea may influence endometrial cancer (EC) risk though causality remains uncertain. This study aimed to investigate potential causal relationships between dysmenorrhea (including pain severity, analgesic use, endometriosis, and related pelvic pain) and EC risk using a Mendelian randomization (MR) approach. Methods: A two-sample MR analysis was conducted using genome-wide association study (GWAS) data, selecting single nucleotide polymorphisms (SNPs) significantly associated with dysmenorrhea to assess EC risk. Primary analysis was performed with the inverse-variance weighted (IVW) method, while weighted median and MR-Egger analyses were conducted to enhance robustness. Results: The IVW analysis showed a significant inverse association between dysmenorrhea and EC risk (OR = 0.883; 95% CI: 0.794-0.983; and p=0.023), which remained significant after adjusting for confounders (OR = 0.868; 95% CI: 0.775-0.971; and p=0.0136). Sensitivity analyses supported this protective association. Other factors, including pain severity, analgesic use, endometriosis, and related pelvic pain, showed no significant association with EC. Conclusion: This study indicates a potential inverse relationship between dysmenorrhea and EC risk. These findings provide novel causal evidence for understanding complex associations in female reproductive health, underscoring the need for further research on dysmenorrhea in EC prevention.