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

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Abstract
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.

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