Associations Between Reproductive and Hormone-related Factors and Risk of Nonalcoholic Fatty Liver Disease in a Multiethnic Population

Abstract Background & Aims Despite apparent sex differences in the prevalence and incidence of nonalcoholic fatty liver disease (NAFLD), there are limited epidemiologic data regarding the associations of reproductive and hormone-related factors with NAFLD. We examined the associations of these factors and exogenous hormone use with NAFLD risk in African American, Japanese American, Latino, Native Hawaiian, and white women. Methods We conducted a nested case–control study (1861 cases and 17,664 controls) in the Multiethnic Cohort Study. NAFLD cases were identified using Medicare claims data; controls were selected among participants without liver disease and individually matched to cases by birth year, ethnicity, and length of Medicare enrollment. Reproductive and hormone-related factors and covariates were obtained from the baseline questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs. Results Later age at menarche was inversely associated with NAFLD (Ptrend=.01). Parity, regardless of number of children or age at first birth, was associated with increased risk of NAFLD (OR, 1.25; 95% CI, 1.05–1.48). Oral contraceptive use was also linked to increased risk of NAFLD (OR, 1.14; 95% CI, 1.01–1.29; duration of use Ptrend=.04). Compared to women with natural menopause, those with oophorectomy (OR, 1.41; 95% CI, 1.18–1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11–1.60) had an increased risk of NAFLD. Longer duration of menopause hormone therapy (only estrogen therapy) was linked with increasing risk of NAFLD (OR per 5 years of use, 1.08, 95% CI, 1.01–1.15). Conclusions Findings from a large multiethnic study support the concept that menstrual and reproductive factors, as well as use of exogenous hormones, associate with risk of NAFLD.