Introduction

The incidence of oesophago-gastric cancer has an age-dependent male predominance mirroring physiological changes in sex hormonal levels. Some previous studies suggest that menopausal hormone therapy (MHT) counteracts the occurrence of these tumours, but larger studies with longer follow-up and adjustment for confounders are needed, which prompted the present study.

Aims & Methods

To investigate the hypothesis that MHT decreases the risk of developing oesophago-gastric cancer, especially oesophageal adenocarcinoma.
This population-based case-control study included women aged ≥45 years in all five Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) between 1995-2020. Prospectively collected data came from national complete registries for medications, cancer, diagnoses, total populations, and death. The study included 19,518 case patients with oesophago-gastric cancer and 195,094 randomly identified control participants matched for age, country and calendar year. The participants were categorised into three equal-sized groups (tertiles) of defined daily doses (DDD) of MHT, with non-users as the reference group. MHT was also categorized as systemic or local, and oestrogen only or oestrogen combined with progesterone MHT. Oesophago-gastric cancer was divided into oesophageal or cardia adenocarcinoma, oesophageal squamous cell carcinoma, and gastric non-cardia adenocarcinoma as separate outcomes. Conditional logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, calendar year, country, obesity, gastroesophageal reflux disease, smoking, alcohol, Helicobacter pylori eradication, use of statins and non-steroidal anti-inflammatory drugs.

Results

​Compared to non-users of MHT, the adjusted ORs of oesophageal or cardia adenocarcinoma were 0.74 (95% CI 0.67-0.81) for low MHT-use (<158 DDDs), 0.68 (95% CI 0.61-0.75) for intermediate MHT-use (158-848 DDDs), and 0.68 (95% CI 0.61-0.75) for high MHT-use (>848 DDDs). The corresponding ORs were 0.69 (95% CI 0.62-0.77), 0.70 (95% CI 0.62-0.77), and 0.71 (95% CI 0.64-0.79) for oesophageal squamous cell carcinoma, and 0.90 (95% CI 0.84-0.96), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86) for gastric non-cardia adenocarcinoma.

Table. Odds ratios (OR) and 95% confidence intervals (CI) of oesophago-gastric cancer by tertiles of defined daily doses (DDD) of menopausal hormone therapy (MHT), MHT hormonal constitution and administration of MHT.

Conclusion

This study provides support for the hypothesis of an inverse association between MHT and risk of developing oesophago-gastric cancer, and particularly for oesophageal adenocarcinoma where the association was seemingly dose-dependent and stronger for combined oestrogen and progesterone MHT and for systemic MHT. A limitation to the study was the inability to adjust for socioeconomic factors as confounders.

Introduction

Treatment response in patients with severe erosive gastroesophageal reflux disease (eGERD) is often inadequate using regular doses of proton pump inhibitors (PPIs), thus necessitating escalation of dosing. High-dose PPIs improve compliance in such patients, leading to better outcomes. However, comparative data on effectiveness of high-dose PPIs is limited.

Aims & Methods

This interim analysis assessed symptomatic improvement of regurgitation in an ongoing, prospective, real-world, observational study to compare the effectiveness of rabeprazole 40mg to pantoprazole 80mg and omeprazole 40mg/esomeprazole 80mg. Adult patients with endoscopically confirmed severe eGERD were enrolled. Patients shifted from low-dose PPIs or started on high-dose PPIs were included; those with complications of GERD were excluded.

Results

A total of 260 patients (rabeprazole, 130; omeprazole/esomeprazole, 65; pantoprazole, 65) from 37 sites in India were analyzed. Although symptomatic improvement of diurnal and nocturnal regurgitation based on patient-reported severity scores was observed among the three arms after 4±1 weeks of treatment, the complete-resolution rate of diurnal regurgitation was significantly higher with rabeprazole (17.97%) compared to omeprazole/esomeprazole (5.08%; p=0.018) and higher than pantoprazole (8.20%; p=0.077). Similarly, complete resolution of nocturnal regurgitation was significantly higher with rabeprazole (14.06%) compared to omeprazole/esomeprazole (1.59%; p=0.007) and higher than pantoprazole (7.94%; p=0.221). Among patients with associated work-related stress (n=132), one-fifth in the rabeprazole arm experienced complete resolution of diurnal regurgitation compared to none in the omeprazole/esomeprazole (p=0.013) or pantoprazole (p=0.030) arms. Patients with lack of regular physical exercise (83.08%) exhibited higher rate of complete resolution of nocturnal regurgitation with rabeprazole (13.73%) compared to the other PPIs. Overall, elderly patients >60 years of age (mean±SD, 68.82±6.54 years) treated with rabeprazole showed significantly higher complete-resolution rates of diurnal regurgitation compared to pantoprazole (36.67% vs. 0%; p=0.003). For complete resolution of nocturnal regurgitation, rabeprazole proved to be significantly better when compared to omeprazole/esomeprazole (31.25% vs. 0%; p=0.015) in elderly patients (Table 1).

Conclusion

The interim results showed that rabeprazole led to significantly higher complete-resolution rates of diurnal and nocturnal regurgitation at 4±1 weeks of treatment than omeprazole/esomeprazole in adults with severe eGERD. In elderly patients, rabeprazole showed significant resolution over pantoprazole.

Disclosure

Study funded by: Dr. Reddy's Laboratories Ltd., Hyderabad, Telangana, India