Menopausal hormone therapy and risk of oesophageal adenocarcinoma in a population-based cohort study

Oesophageal adenocarcinoma is characterised by a strong male predominance. We aimed to test the hypothesis that menopausal hormonal therapy decreases the risk of oesophageal adenocarcinoma.

This population-based cohort study included all women who used systemic menopausal hormonal therapy (exposed) in Sweden between 2005 and 2018. For each exposed participant, five randomly selected female age-matched non-users of menopausal hormonal therapy (unexposed) were included. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking-related diagnoses, Helicobacter pylori eradication, use of non-steroidal anti-inflammatory drugs/aspirin, use of statins and hysterectomy.

The study included 296,964 users of menopausal hormonal therapy and 1,484,820 non-users. Ever-users of menopausal hormonal therapy had an overall decreased risk of oesophageal adenocarcinoma (HR 0.78, 95% CI 0.63-0.97), which remained unchanged after further adjustment for gastro-oesophageal reflux disease (HR 0.78, 95% CI 0.63-0.97) and obesity/diabetes (HR 0.79, 95% CI 0.63-0.98). Decreased HRs were indicated both in users of oestrogen only (HR 0.82, 95% CI 0.60-1.12) and oestrogen combined with progestogen (HR 0.75, 95% CI 0.56-1.00). The risk reduction was more pronounced in users younger than 60 years (HR 0.57, 95% CI 0.38-0.86).

Menopausal hormone therapy in women may decrease the risk of oesophageal adenocarcinoma.