This article is more than 5 years old. Information may no longer be current.

Postmenopausal estrogen use reduces risk for HCC

New data revealed an association between postmenopausal estrogen use and a reduced risk for hepatocellular carcinoma and increased overall survival time in women with HCC.

“In view of the notable male predominance of HCC, several investigators raised the question about the importance of sex hormones in HCC risk and prognosis. The liver expresses estrogen and androgen receptors, both of which may act as transcription factors and may regulate expression of several regulatory genes involved in several pathways including those associated with cell proliferation and immune response,” the researchers wrote. “This study demonstrates 50% reduction in HCC risk development among women who used [menopause hormone therapy].”

Between Jan. 1, 2004, and May 31, 2015, the researchers enrolled 234 women with HCC and 282 women controls for the study. Patients were asked about their age of menarche, age of menopause and the history and details of hysterectomy, any birth control use and of pregnancy.

Significant demographic risk factors associated with HCC in women included non-white ethnicity (adjusted odds ratio = 0.27; 95% CI, 0.14-0.55), HCV (aOR = 71.6; 95% CI, 9.6-536.04), positive HBsAg (aOR = 13.95; 95% CI, 1.28-151.58) or anti-HBc (aOR = 2.98; 95% CI, 1.1-8.07), alcohol consumption (aOR = 2.9; 95% CI, 1.81-4.64), history of diabetes (aOR = 3.84; 95% CI, 1.96-7.5), obesity (aOR = 2.35; 95% CI 1-5.18), hypothyroidism (aOR = 2.43; 95% CI, 1.43-4.16) and family history of cancer (aOR = 1.79; 95% CI, 1.07-2.98).

Among the patients with HCC, 146 reported previous use of hormonal birth control. Use of progesterone was not associated with a reduced risk for HCC in the study cohort. Sixty-three patients with HCC reported using estrogen alone and this was associated with a reduced risk for HCC (aOR = 0.5; 95% CI, 0.29-0.86), compared with non-users. Use of any estrogen by duration remained significant in association with reduced risk for HCC at 5 years or less (aOR = 0.56; 95% CI, 0.34-1.02), 6 to 10 years (aOR = 0.32; 95% CI, 0.13-0.77) and more than 10 years (aOR = 0.45; 95% CI, 0.24-0.85).

Estrogen use was mainly found in patients (87 of 94) and controls (177 of 179) who were postmenopausal. Mean age of HCC onset was higher in patients with history of estrogen use compared with non-users (64.5 vs. 59.2 years; P = .001). Overall survival time was longer among patients with history of estrogen use compared with non-users (P = .008). After controlling for all confounding factors of HCC overall survival, estrogen use was significantly associated with a 45% reduced mortality rate (adjusted hazard ratio = 0.55; 95% CI, 0.4-0.77).

“This study provides robust epidemiological evidence for the benefits of postmenopausal use of estrogen replacement against HCC development and has been corroborated by previous studies,” the researchers wrote. “This study ... [highlights] survival improvement among women with HCC who used estrogen replacement, after controlling for clinical prognostic factors, which raises the questions of whether similar effects can be observed in men who ever experienced hormonal exposure and whether estrogen can be used in targeted therapy for a selected population based on tumor expression and types of estrogen receptors.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.