Long or Irregular Menstrual Cycles and Risk of Prevalent and Incident Nonalcoholic Fatty Liver Disease

Abstract

Context: The association of menstrual cycle length and irregularity with the risk of non-alcoholic fatty liver disease (NAFLD) is unknown. Objective: We examined this association in large cross-sectional and cohort studies. Methods: The cross-sectional study included 72 092 women younger than 40 years who underwent routine health examinations; the longitudinal analysis included the subset of 51 118 women without NAFLD at baseline. Long or irregular cycles were defined as menstrual cycles of 40 days or longer or too irregular to estimate. Abdominal ultrasonography was performed to identify NAFLD. Multivariable Cox proportional hazard regression analyses were performed to estimate hazard ratios (HRs) and 95% CIs for incident NAFLD according to menstrual cycle regularity and length, with 26- to 30-day cycles as the reference. Results: At baseline, 27.7% had long or irregular menstrual cycles and 7.1% had prevalent NAFLD. Long or irregular menstrual cycles were positively associated with prevalent NAFLD. During a median follow-up of 4.4 years, incident NAFLD occurred in 8.9% of women. After adjustment for age, body mass index, insulin resistance, and other confounders, the multivariable-adjusted HR for NAFLD comparing long or irregular menstrual cycles to the reference group was 1.22 (95% CI, 1.14-1.31); this association strengthened in the time-dependent analysis with an HR of 1.49 (95% CI, 1.38-1.60). Conclusion: Long or irregular menstrual cycles were associated with increased risk of both prevalent and incident NAFLD in young, premenopausal women. Women with long or irregular menstrual cycles may benefit from lifestyle modification advice to reduce the risk of NAFLD and associated cardiometabolic diseases.