Abstract
BACKGROUND: Many studies suggested that menstrual and reproductive factors affected the gender disparity in liver carcinogenesis, but the results were inconsistent. Moreover, there are few studies in Asian populations. Therefore, our study was to explore the association of menstrual and reproductive factors on liver cancer risk in Chinese women. METHODS: 72,807 women were recruited in 1996 to 2000 and followed until the end of 2016 in Shanghai, China. Cox regression models were used to estimate HRs and 95% confidence intervals (CIs) for the association of menstrual and reproductive factors with liver cancer. RESULTS: 258 liver cancer cases were identified during 1,269,531 person-years of follow-up. In premenopausal and postmenopausal women, hormone replacement therapy (HRT) and injective contraceptives were positively associated with liver cancer risk respectively (HR, 1.23, 95% CI, 1.15-1.30; HR, 1.23, 95% CI, 1.17-1.30; HR, 1.07, 95% CI, 1.05-1.10; HR, 1.08, 95% CI, 1.05-1.11), while older age at menopause, longer reproductive period and fewer live births were associated with reduced risk, especially among postmenopausal women (Ptrend < 0.05). In addition, liver cancer risk was elevated in postmenopausal women who received hysterectomy (HR, 1.07; 95% CI, 1.04-1.11), oophorectomy (HR, 1.05; 95% CI, 1.01-1.10) or oral contraceptives (HR, 1.06; 95% CI, 1.03-1.08). No association was found between age at menarche and liver cancer risk. Similar results were observed when excluding participants with less than 2 follow-up years. CONCLUSIONS: The findings suggested that female sex hormones could play significant roles in liver carcinogenesis. IMPACT: Our study was the first population-based cohort to provide epidemiology evidence of menstrual and reproductive factors on liver cancer risk in Chinese women.