Menstrual Factors, Reproductive History and Liver Cancer Risk: Findings from a Prospective Cohort Study in Chinese Women

Background: Many studies suggested that menstrual and repro-ductive 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 asso-ciation 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 reproduc-tive 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 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.