Long or irregular menstrual cycles were found to be associated with increased risk of prevalent and incident nonalcoholic fatty liver disease (NAFLD) among young, premenopausal women, according to the results of a study published in the Journal of Clinical Endocrinology & Metabolism.
The finding is based on analysis of data from the Kangbuk Samsung Health Study, which included premenopausal Korean women aged younger than 40 years. The women underwent comprehensive health examinations from 2011 to 2017, as well as at least 1 follow-up examination by December 31, 2019. The primary outcome was development of NAFLD.
The cross-sectional analysis included 72,092 women, and the longitudinal analysis included a subgroup of 51,118 women without NAFLD at baseline. The women were categorized according to menstrual cycle (<21 days, 21-25 days, 26-30 days, 31-39 days, and ≥40 days or irregular). Mean ages in the groups ranged from 31.3 years in those with a menstrual cycle <21 days to 33.5 years in those with a menstrual cycle ranging from 21 to 35 days.
At baseline, 7.1% of the women had prevalent NAFLD, and 27.7% had long (≥40-day) or irregular menstrual cycles. Women with menstrual cycles less than 21 days, 31 to 39 days, and at least 40 days or irregular had a higher prevalence of NAFLD, with age-adjusted prevalence ratios (95% CIs) of 1.21 (1.07-1.36), 1.35 (1.29-1.41), and 1.89 (1.83-1.95), respectively, compared with women who had menstrual cycles ranging from 26 to 30 days as the reference.
After further adjustment for center, examination year, alcohol consumption, smoking status, health-enhancing physical activity, education level, parity, age at menarche, body mass index, and homeostatic model assessment of insulin resistance (HOMA-IR), 31- to 39-day and at least 40-day or irregular cycles were associated with NAFLD, with prevalence ratios (95% CIs) of 1.27 (1.19-1.36) and 1.35 (1.28-1.42), respectively.
Among women without NAFLD at baseline, 4524 incident cases of NAFLD occurred after a mean follow-up of 4.4 years. Regarding longitudinal associations between menstrual cycle categories and incident NAFLD, less than 21-day, 31- to 39-day, and at least 0-day or irregular menstrual cycles were associated with NAFLD, with age-adjusted hazard ratios (95% CIs) of 1.54 (1.19-1.99), 1.13 (1.03-1.24), and 1.26 (1.18-1.35), respectively. Time-dependent analysis revealed that 31-day to 39-day and at least 40-day or irregular cycles were associated with increased risk of incident NAFLD, with hazard ratios (95% CIs) of 1.27 (1.15-1.39) and 1.49 (1.38-1.60), respectively, compared with the reference group.
In subgroup analyses, 31-day to 39-day and at least 40-day or irregular menstrual cycles were associated with increased risk of NAFLD with HOMA-IR less than 2.5, with adjusted hazard ratios (95% CIs) of 1.18 (1.08-1.30) and 1.27 (1.18- 1.37), respectively, but not with HOMA-IR of at least 2.5 (P for interaction = .001).
Among the women with pelvic ultrasonography data and gynecologic assessments available, after exclusion of 300 participants with suspected polycystic ovary syndrome (PCOS), in the cross-sectional analysis, 31-day to 39-day and at least 40-day or irregular menstrual cycles were associated with NAFLD, with adjusted prevalence ratios (95% CIs) of 1.28 (1.11-1.46) and 1.42 (1.27-1.58), respectively. For the longitudinal analysis of 14,378 women without NAFLD or suspected PCOS at baseline, the adjusted hazard ratios (95% CIs) for 31-day to 39-day and at least 40-day or irregular menstrual cycles were 1.23 (1.03-1.47) and 1.32 (1.15-1.52), respectively.
Among several study limitations, menstrual cycle was assessed with use of self-administered questionnaires, and the researchers did not have information regarding women’s sex hormone or prolactin levels or biochemical hyperandrogenism. In addition, the cohort included only relatively healthy, young premenopausal Korean women.
“Screening for NAFLD and counseling to promote healthy lifestyle behaviors may benefit women with a history of long or irregular menstrual cycles,” the researchers commented.
Cho IY, Chang Y, Kang J-H, et al. Long or irregular menstrual cycles and risk of prevalent and incident nonalcoholic fatty liver disease. J Clin Endocrinol Metab. Published online March 3, 2022. doi: 10.1210/clinem/dgac068