Hormone replacement therapy and risk of glioma: A nationwide nested case–control study

Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma in a nationwide setting. Methods: Using population-based registries we conducted a case–control study nested in the Danish female population. We identified all women aged 55–84 years with a first diagnosis of histologically verified brain glioma during 2000–2009. Using risk-set sampling, each case was matched on birth year to eight population controls. Ever use of HRT was defined as ≥2 HRT prescriptions and categorized according to type (oestrogens only, combined oestrogen-progestagen and progestagen only) and duration of use (<1, ≥1 to <5, ≥5 to <10, and ≥10 years). We used conditional logistic regression to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with HRT use, adjusting for potential confounders. Results: We identified 658 cases and 4350 controls. Ever use of HRT was associated with an OR of 0.9 (95% CI: 0.8–1.1) for glioma. For long-term use (≥10 years) we found ORs of 1.1 (95% CI: 0.7–1.7) for HRT overall, 1.6 (95% CI: 0.9–2.6) for oestrogen only, 0.8 (0.4–1.6) for combined oestrogen-progestagen, and 2.2 (0.9–5.5) for progestagen. Tests for trends were statistically non-significant in all strata. Conclusion: Use of HRT overall was not associated with an increased risk of glioma. However, our findings indicate that prolonged use of oestrogen only or progestagen may be associated with an increased risk of glioma.