Abstract 879: Menopausal hormone therapy and risk of primary liver cancer in the UK Clinical Practice Research Datalink

Background: The incidence of primary liver cancer (PLC) is three to four times higher among males than females in almost all countries. The discrepancy in rates is particularly notable prior to menopause, suggesting that estrogen exposure may be associated with lower risk. The relationship of menopausal hormone therapy (MHT) use to risk of PLC among women, however, has not been extensively examined. Methods: We conducted a nested case-control study among women in the U.K.9s Clinical Practice Research Datalink (CPRD). Women diagnosed with primary liver cancer (n = 339) between 1988 and 2011 were matched to controls at a 4:1 ratio on age, index year, general practice and length of history in the CPRD. Odds ratios (OR) and 95% confidence intervals (95%CI) for associations of MHT with PLC were estimated using conditional logistic regression. All models were conditioned on the matching factors and adjusted for body mass index, HBV, HCV, smoking, alcohol-related disorders, diabetes, rare metabolic disorders, history of a bilateral oophorectomy, and use of certain medications, including paracetamol, aspirin, anti-diabetes therapies, and statins. Results: Use of MHT for 6 months or longer was associated with a significantly lower risk of PLC (OR = 0.60, 95%CI = 0.39-0.92). Examination by length of MHT use found that use between 6-30 months was associated with significantly reduced risk (OR = 0.47, 95%CI = 0.24-0.91), while use greater than 30 months did not attain statistical significance (OR = 0.68, 95%CI = 0.41-1.13). When MHT was stratified by formulation (estrogen-only vs estrogen/progesterone), estrogen-only use was associated with significantly lower risk of PLC (OR = 0.51, 95%CI = 0.26-0.97) while estrogen/progesterone use did not attain statistical significance (OR = 0.65, 95%CI = 0.39-1.08). Conclusion: MHT use, in particular estrogen-only MHT use, may be associated with lower risk of PLC. These findings are consistent with rodent models which have reported suppression of both fatty liver and hepatocarcinogenesis with administration of estrogen. As the association in the current study was apparent among users of 6-30 months, even short-term use of estrogen-only MHT may reduce risk. Citation Format: Katherine A. McGlynn, Katrina Hagberg, Jie Chen, Susan Jick, Vikrant V. Sahasrabuddhe. Menopausal hormone therapy and risk of primary liver cancer in the UK Clinical Practice Research Datalink. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 879. doi:10.1158/1538-7445.AM2015-879