Hormone Replacement Therapy and Oral Contraceptives and Risk of Oesophageal Adenocarcinoma: A Systematic Review and Meta-analysis

INTRODUCTION: There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC).  A potential protective influence of exogenous oestrogen exposure, i.e. hormone replacement therapy (HRT) and oral contraceptives (OC) has been addressed only in studies of limited statistical power, and the individual studies have not provided conclusive results.

METHODS : We conducted a systematic literature search and meta-analysis on HRT and OC and the risk of OAC. We used the databases PubMed and the Web of Science (1960-2013). Pooled odds ratios (ORs) and 95% confidence intervals (CIs), estimated by the Mantel-Haenszel random-effect method. Statistical heterogeneity was assessed by the I-square test.

RESULTS : The search identified 463 articles, of which 5 eligible studies published between 2006-2011, including a total of 451 women with OAC and 367,033 female controls. Two studies were cohort studies, and 3 were case-control studies. All studies addressed HRT exposure, while 3 studies also presented data on OC exposure. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR=0.75; 95% CI: 0.58-0.98) and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR=0.76; 95% CI: 0.57-1.00). Statistical heterogeneity was low (I²=0%).

CONCLUSIONS : This study suggests that use of HRT, and possibly also OC, decreases the risk of OAC, thus providing support for the hypothesis that exogenous oestrogen exposure counteracts OAC in women. These findings require more research before any causal association can be established. This meta-analysis was limited by the low number of studies, and there was insufficient data to allow sub-group analysis of duration, type or dosage of HRT and OC use, or adjust for potential confounding. The rough categorisation into ever or never use should, however, dilute true effects rather than enhance them since potential misclassification was likely to be non-differential.