Menopausal hormone therapy and risk of gastrointestinal cancer: Nested case–control study within a prospective cohort, and meta‐analysis

Use of menopausal hormone therapy (HT) has been associated with reduced risk of colorectal cancer; evidence for its effect on other gastrointestinal cancers is limited. We conducted a nested case-control study within a UK cohort, and meta-analyses combining our results with those from published studies. Our study included women aged 50+ in the UK General Practice Research Database (GPRD): 1,054 with oesophageal, 750 with gastric and 4,708 with colorectal cancer, and 5 age- and practice-matched controls per case. Relative risks (RRs) and 95% confidence intervals (CIs) for cancer in relation to prospectively-recorded HT prescriptions were estimated by conditional logistic regression. Women prescribed HT had a reduced risk of oesophageal cancer (adjusted RR for 1+ vs. no HT prescriptions, 0.68, 95% CI 0.53-0.88; p = 0.004), gastric cancer (0.75, 0.54-1.05; p = 0.1) and colorectal cancer (0.81, 0.73-0.90; p < 0.001). There were no significant differences in cancer risk by HT type, estimated duration of HT use or between past and current users. In meta-analyses, risks for ever vs. never use of HT were significantly reduced for all three cancers (summary RR for oesophageal cancer, 0.68, 0.55-0.84, p < 0.001; for gastric cancer, 0.78, 0.65-0.94, p = 0.008; for colorectal cancer, 0.84, 0.81-0.88, p < 0.001). In high-income countries, estimated incidence over 5 years of these three cancers combined in women aged 50-64 was 2.9/1,000 in HT users and 3.6/1,000 in never users. The absolute reduction in risk of these cancers in HT users is small compared to the HT-associated increased risk of breast cancer.