Raloxifene increases the risk of gastroesophageal reflux disease, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis

Benjamin D Liu; Sharon C Udemba; Sherif Saleh; Hannah Hill; Gengqing Song; Ronnie Fass

doi:10.1111/nmo.14689

Raloxifene increases the risk of gastroesophageal reflux disease, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis

Neurogastroenterol Motil. 2023 Dec;35(12):e14689. doi: 10.1111/nmo.14689. Epub 2023 Oct 9.

Authors

Benjamin D Liu¹, Sharon C Udemba¹, Sherif Saleh¹, Hannah Hill², Gengqing Song³, Ronnie Fass³

Affiliations

¹ Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
² Population Health and Equity Research Institute, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
³ Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.

PMID: 37807850
DOI: 10.1111/nmo.14689

Abstract

Background and aims: Estrogen-based therapies may increase the risk of gastroesophageal reflux (GERD) and its complications. We aimed to determine the effect of raloxifene on the development of GERD, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis.

Methods: This was a population-based, propensity-matched cohort study using the TriNetX platform. Patients 50 years and older with a diagnosis of "menopause" and "osteoporosis" were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for new GERD, esophageal stricture and Barrett's esophagus after raloxifene exposure. The control cohort consisted of patients who did not start any hormonal replacement therapy. We conducted a multivariable logistic regression analysis to evaluate the effect of confounding variables and also addressed common confounding medications with 1:1 propensity score-matching. Internal validity was confirmed by comparing to negative controls (lisinopril, atorvastatin) and positive controls (metformin, ibuprofen, aspirin).

Results: Five thousand four hundred and seventy two postmenopausal women with osteoporosis were on raloxifene of which 1908 (34.86%) developed GERD, compared to 296,067 postmenopausal who were not on raloxifene of which 90,643 (30.62%) developed GERD (OR 1.2; 95% CI 1.10-1.31, p < 0.0001). This persisted after adjusting for common medications known to affect GERD. Raloxifene was identified as a risk factor for GERD in a multivariate analysis, controlling for factors including age, obesity, smoking, and alcohol use (OR 1.51, 95% Wald CI 1.47-1.53). Raloxifene was associated with esophageal stricture (OR 1.60; 95% Wald CI 1.51-1.69) and Barrett's esophagus (OR 1.50; 95% Wald CI 1.37-1.63) in multivariate analysis. These associations persisted using sensitivity analyses.

Conclusion: Raloxifene increases the risk of GERD, esophageal stricture and Barrett's esophagus in postmenopausal women with osteoporosis. Further studies are needed to confirm our findings.

Keywords: Barrett's esophagus; esophageal stricture; gastroesophageal reflux disease; postmenopausal women; raloxifene.

MeSH terms

Barrett Esophagus* / diagnosis
Barrett Esophagus* / epidemiology
Case-Control Studies
Cohort Studies
Esophageal Stenosis*
Female
Gastroesophageal Reflux* / complications
Gastroesophageal Reflux* / diagnosis
Gastroesophageal Reflux* / drug therapy
Humans
Osteoporosis* / complications
Postmenopause
Raloxifene Hydrochloride / adverse effects
Risk Factors

Substances

Raloxifene Hydrochloride