Better survival in female patients with hepatocellular carcinoma: oral contraceptive pills related?

BACKGROUND: Hepatocellular carcinoma (HCC) has an indisputable male predominance. "Gender" as an independent prognostic factor for survival is, however, controversial. GOALS: Determine the influence of gender on survival in HCC patients, and identify factors that may account for the difference.
METHODS: A retrospective analysis on a prospectively collected database in a 15-year period, from 1989 to 2003.
RESULTS: A total of 3,171 HCC patients were managed in our institution (946 with curative treatment, 1,388 with palliative treatment, and 837 with supportive treatment) and studied. Female patients (n = 520) were 4.3 years older (P = 0.000), had a lower proportion of smokers and drinkers (P = 0.000), and were less likely to be hepatitis B carriers (P = 0.000). There was no difference in Child-Pugh status, tumor size, and the use of different treatments between genders. The overall median survival was 25.7 months longer in females after curative treatment (73.6 vs. 47.9 months; P = 0.012). The survival benefit in female patients was observed in early-stage diseases and persisted when only hepatitis B surface antigen-positive patients were analyzed (96.4 vs. 47.9 months; P = 0.044). With multivariate analysis, gender, indocyanine green test value at 15 minutes, number of tumor nodules, size of tumor, major vascular invasion, invasion of adjacent organs, and tumor rupture were the independent variables for survival. More importantly, in female patients, history of using oral contraceptive was an independent factor with survival benefit (P = 0.004).
CONCLUSION: Gender is an independent variable for survival after curative treatment of HCC. A survival benefit was observed in females. History of using oral contraceptive is associated with a better long-term survival in female patients.