Background: Gynecologic cancers, including cervical, endometrial, and ovarian cancers, remain a major global health burden. Although histamine-2 receptor antagonists (H2RAs) are inexpensive and widely accessible agents with reported anticancer properties, their associations with gynecologic cancer risk remain unclear. This study evaluated the potential of H2RAs for repurposing in chemoprevention.
Methods: A nationwide, population-based case-control study was conducted using Taiwan's National Health Insurance claims and Cancer Registry data from 2002 to 2016. A total of 97,736 women with newly diagnosed gynecologic cancer were matched 1:4 with controls by sex, age (±5 years), and month and year of diagnosis. H2RA exposure was defined as >60 days of use within two years before the index date. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression, adjusting for age, Charlson Comorbidity Index, and use of metformin, aspirin, and statins.
Results: H2RA use was associated with reduced risks of cervical (aOR 0.80), endometrial (0.68), and ovarian cancers (0.78). Age-stratified analyses showed lower risks of cervical and endometrial cancers across all age groups, while reduced ovarian cancer risk was most evident in women aged 40-64. Individual H2RA agents showed protective effects in the overall population, with cimetidine demonstrating the broadest reduction.
Conclusions: Long-term H2RA use was associated with lower risks of major gynecologic cancers, with notable age- and agent-specific differences. Prospective studies are warranted to confirm causality and inform clinical application.
Impact: Findings support repurposing H2RAs as accessible chemopreventive candidates for further translational application in women.