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The Potential Impact of Histamine-2 Receptor Antagonists on Gynecologic Cancer Risk: A Population-Based Study of 23
Chao-Jung Chiang1, Nhi Thi Hong Nguyen2,3, Chih-Wei Huang4,5
1School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Background:
Gynecologic cancers, including cervical, endometrial, and ovarian cancers, remain a major global health burden. Although histamine-2 receptor antagonists (H2RA) 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 (aOR) and 95% confidence intervals 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, whereas the reduced ovarian cancer risk was most evident in women aged 40 to 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.
Insights
Histamine-2 receptor antagonists (H2RAs) show promise in lowering the risk of cervical, endometrial, and ovarian cancers. These findings suggest H2RAs could be repurposed for gynecologic cancer chemoprevention.
Area of Science:
- Oncology
- Pharmacology
- Epidemiology
Background:
- Gynecologic cancers pose a significant global health challenge.
- Histamine-2 receptor antagonists (H2RAs) have demonstrated anticancer properties but their role in gynecologic cancer prevention is not well-established.
Purpose of the Study:
- To investigate the association between H2RA use and the risk of developing cervical, endometrial, and ovarian cancers.
- To evaluate the potential of repurposing H2RAs for chemoprevention strategies in women.
Main Methods:
- A population-based case-control study utilizing nationwide health insurance and cancer registry data (2002-2016).
- 97,736 women with gynecologic cancer were matched 1:4 with controls.
- H2RA exposure defined as >60 days use within two years prior to diagnosis; adjusted logistic regression analysis was performed.
Main Results:
- H2RA use was linked to reduced risks of cervical (aOR 0.80), endometrial (aOR 0.68), and ovarian cancers (aOR 0.78).
- Protective effects were observed across various age groups, with notable differences for ovarian cancer risk in women aged 40-64.
- Cimetidine showed the most significant protective effect among individual H2RA agents.
Conclusions:
- Long-term H2RA use is associated with decreased risks of major gynecologic cancers.
- Age and specific H2RA agents influence the protective effects.
- H2RAs represent potential candidates for accessible chemoprevention and warrant further clinical investigation.
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