A hypothesis on the aetiology of adenomyosis: is there an association between cumulative number of menstruations and severity of adenomyosis on ultrasound?

Rationale: Adenomyosis is a common uterine disorder, yet its aetiology remains debated. The tissue injury and repair (TIAR) hypothesis suggests that repeated microtrauma from menstrual contractions damages the endometrial-myometrial interface, thereby contributing to development and progression of adenomyosis. We investigated whether cumulative menstrual exposure is associated with severity of adenomyosis on ultrasound. Methods: This exploratory retrospective study was conducted at Amsterdam University Medical Centre, as a sub-analysis of the prospective Results: We included 119 participants in the final analysis. The median age of the study population was 27 years, of whom 79% were nulliparous and 14% had a history of uterine surgery. Previous hormonal menstruation suppression with the oral contraceptive pill was reported by 87% of participants, with a median duration of use of 7 years. In addition, 32% had previously used a hormonal intrauterine device, with a median duration of use of 3 years. Age was excluded from multivariable analyses due to collinearity (r = 0.72). After adjustment for vaginal births and uterine surgeries, cumulative menstrual exposure was associated with severity of adenomyosis (β=0.003; 95% CI 1.001-1.006; p < 0.05). Conclusion: Higher cumulative menstrual exposure was associated with increased severity of adenomyosis, supporting the TIAR hypothesis. Given the retrospective study design and collinearity with age, results should be interpreted with caution.