{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:42:03Z","timestamp":1788356523735,"version":"build-2803163510"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4292,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Hepatocellular 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\u2013control 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)\u2013positive and \u2013negative 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\u2013degree female relatives of patients with HCC. The risk of HCC was inversely related to the number of full\u2013term pregnancies (FTP) (<jats:italic toggle=\"yes\">P<\/jats:italic>\n                                 <jats:sub>trend<\/jats:sub> = .0216) and age at natural menopause (<jats:italic toggle=\"yes\">P<\/jats:italic>\n                                 <jats:sub>trend<\/jats:sub> = .0251 among women aged 45\u201355 without prior surgical menopause). Oophorectomy at age \u226450 during premenopausal years was also a risk factor (multivariate\u2013adjusted OR, 2.57; 95% CI, 1.42\u20134.63). Use of hormone replacement therapy (HRT) (multivariate\u2013adjusted OR, 0.46; 95% CI, 0.27\u20130.79) was associated with a lower risk of HCC, and there was a trend in the risk with increasing duration of HRT (<jats:italic toggle=\"yes\">P<\/jats:italic>\n                                 <jats:sub>trend<\/jats:sub> = 0.0013). All reproductive factors had a similar impact on HBsAg\u2013positive and \u2013negative women except for an early menarche (\u226412 vs. \u226516 years), which increased HCC risk in HBsAg carriers (multivariate\u2013adjusted OR, 6.96; 95% CI, 2.52\u201319.18) but posed no increased risk in noncarriers (<jats:italic toggle=\"yes\">P<\/jats:italic>\n                                 <jats:sub>interaction<\/jats:sub> = .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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1016\/j.hep.2003.09.041","type":"journal-article","created":{"date-parts":[[2003,11,25]],"date-time":"2003-11-25T20:29:01Z","timestamp":1069792141000},"page":"1393-1400","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":41,"title":["Role of Reproductive Factors in Hepatocellular Carcinoma: Impact on Hepatitis B- and C-Related 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