Author(s): Somtochukwu Onwuzo*, Antoine Boustany, Hadi Khaled Abou Zeid, Chidera Onwuzo, Jessy M Monteiro, Favour Lawrence and Imad Asaad
Background and Aim: In the United States, approximately 40% of post-menopausal women use hormone replacement therapy (HRT); estrogen with or without progesterone. Treatment of menopausal symptoms such as hot flashes, urogenital atrophy is an indicator of short-term use of HRT. However, in some cross-sectional studies, it is reported that women use HRTs for far longer than the intended duration. Over the years, results for most studies showing benefits of HRT were only significant for short-term use of the drug. Grodstein et al. reported decreased incidence of coronary artery disease in current users, but not among ever, past or all use groups. We believe hazardous effects of HRTs are seen in among ever, past groups. The risk of breast cancer, endometrial cancer and cholecystitis is established to be associated with increasing duration of use and risk remained elevated even 5 years after discontinuation. Though we have studies highlighting effects of HRT and reproductive malignancies, the impacts of long-term use of HRT and development of gastrointestinal (GI) malignant neoplasms is lacking. Therefore, we decided to carry out a study highlighting the prevalence of upper GI tumors (gastric, esophageal and pancreatic cancers) in postmenopausal women who have used HRT.
Methodology: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized to construct this study. Females aged 65 years and above were included in the study. Patients with autoimmune diseases were excluded. Three separate multivariate regression analyses, assessing the risk of developing esophageal, stomach, and pancreatic cancer, were performed by controlling for potential cofounders. A two-sided P value <0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008).
Results: 79,368,988 individuals were screened in the database and 11,177,050 were selected in the final analysis after accounting for inclusion and exclusion criteria. The baseline characteristics of patients with esophageal, gastric, and pancreatic cancer is seen in Table 1. Three separate multivariate regression analyses were performed to assess the risk of developing esophageal, gastric, and pancreatic cancer. The odds of having Gastric cancer (GC) in HRT users was increased at 1.74 (95% CI 1.51-1.99), Similarly, the odds of have Pancreatic cancer (PC) in HRT user was also increased at 1.40 (95% CI 1.26-1.56 (Table 2).
Conclusion: Our study shows that, even after adjusting for typical risk variables, gastric and pancreatic cancer are frequently observed among HRT users. This adds to the literature to spread awareness to clinics that the effects HRT are not only limited to female reproductive system as it’s use tend to involve parts of the gastrointestinal system
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