MING-WHEI YUChang H.-C.Chang S.-C.Liaw Y.-F.Lin S.-M.CHUN-JEN LIULee S.-D.Lin C.-L.PEI-JER CHENLin S.-C.Chen C.-J.2021-07-032021-07-0320030270-9139https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984593075&doi=10.1016%2fj.hep.2003.09.041&partnerID=40&md5=16cf59da08037e550bbdea99c25361e0https://scholars.lib.ntu.edu.tw/handle/123456789/568761Hepatocellular carcinoma (HCC) is more prevalent in men than in women. Estrogen may play some role in the development of HCC. We conducted a multicenter case-control study to evaluate the effects of reproductive factors on HCC risk, and to assess whether the association between each factor and HCC differs between hepatitis B surface antigen (HBsAg)-positive and -negative women, in which hepatitis C virus (HCV) is the major cause of HCC. The study included 218 women with HCC and 729 control women selected from nonbiological and first-degree female relatives of patients with HCC. The risk of HCC was inversely related to the number of full-term pregnancies (FTP) (P trend = .0216) and age at natural menopause (Ptrend = .0251 among women aged 45-55 without prior surgical menopause). Oophorectomy at age<50 during premenopausal years was also a risk factor (multivariate-adjusted OR, 2.57; 95% CI, 1.42-4.63). Use of hormone replacement therapy (HRT) (multivariate-adjusted OR, 0.46; 95% CI, 0.27-0.79) was associated with a lower risk of HCC, and there was a trend in the risk with increasing duration of HRT (Ptrend = 0.0013). All reproductive factors had a similar impact on HBsAg-positive and -negative women except for an early menarche (? 12 vs. > 16 years), which increased HCC risk in HBsAg carriers (multivariate-adjusted OR, 6.96; 95% CI, 2.52-19.18) but posed no increased risk in noncarriers (Pinteraction = .0053). In conclusion, increased exposure to estrogen during adulthood may provide a protective effect against HCC. Nevertheless, an early menarche, which results in early estrogen exposure, does not confer protection for HBsAg carriers.[SDGs]SDG3adult; aged; article; controlled study; disease association; female; genetic heterogeneity; hepatitis B; Hepatitis B virus; hepatitis C; Hepatitis C virus; hormone substitution; human; liver cell carcinoma; major clinical study; menarche; menopause; multivariate analysis; ovariectomy; pregnancy; priority journal; risk factorjournal article10.1016/j.hep.2003.09.041146470502-s2.0-84984593075