Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma

Abstract

Background & Aims Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. We investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. Methods We performed a case–control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls), from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. Results The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% CI, 0.32–0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5±0.9 years) vs non-users (mean, 59.2±1.1 years) (P=.001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20– 0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67–11.44) vs AOR for non-users, 17.60 (95% CI, 3.88–79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40–0.77) (P=.01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7–41.3 months) and 24.1 months for non-users (95% CI, 19.02–29.30 months) (P=.008). Conclusion In a case–control study of women with HCC vs female controls at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.

Nomograms to predict the long‐time prognosis in patients with alpha‐fetoprotein negative hepatocellular carcinoma following radical resection

“…Interestingly, sex represented a large weighting in the nomogram for RFS and was significantly associated with HCC recurrence. Previous studies have found that men were more likely to develop HCC than women, and male patients were more prone to relapse than female patients in 2 years after hepatectomy . This sex difference may be related to sex hormones and requires additional study.…”

Sex Hormone-Dependent Physiology and Diseases of Liver

“…The HBV contagion and subsequent consequences of infection are different in males and females [83][84][85][86][87][88][89]. The effects of sex differences, especially sex hormones, on the innate immune response to HBV are largely unknown, which is at least partly due to the lack of appropriate research models.…”

Impact of gender as a prognostic factor in HBV-related Hepatocellular Carcinoma: the survival strength of female patients in BCLC stage 0-B

“…Different male to female ratios can also be observed in different locations [4] . Sex hormones play an important role in these gender-related incidences i.e., androgens stimulate the androgen signaling pathway while estrogen probably plays a protective role during HCC development or outcome [7][8][9] . However, there has been some controversy about the role of gender with respect to HCC prognosis in recent years.…”