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

Abstract

There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves attention. A potential protective influence of exogenous oestrogen exposure, that is, 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. 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. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the Mantel-Haenszel random-effect method. A total of five studies were included. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR 5 0.75; 95% CI: 0.58-0.98), and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR 5 0.76; 95% CI: 0.57-1.00). In conclusion, HRT and OC use seems to be associated with a decreased risk of OAC. However, further research is warranted.Oesophageal adenocarcinoma (OAC) is up to nine times more common in men than women, yet the reasons behind this pattern remain unclear. 1,2 Gastro-oesophageal reflux and high body mass index (BMI), the two main risk factors for OAC, seem to influence the risk of developing OAC similarly in both genders, and might not explain the male predominance. [3][4][5][6] The typical male fat distribution, with mainly abdominal adiposity, is a stronger risk factor for OAC than BMI alone, 7 but it is uncertain if this exposure contributes the sex ratio of OAC. 8 It has also been hypothesised that female sex hormones, mainly oestrogen, are protective. This oestrogen hypothesis is supported by a 20-year delay in the onset of OAC in women compared to men, 9 and a particularly high male-to-female ratio during women's reproductive years. 10 Individual investigations of the potential role of exogenous hormonal therapy in women, including hormone replacement therapy (HRT) and oral contraceptives (OC), in the aetiology of OAC have failed to provide conclusive results. 11-15 The low incidence of OAC in women has hampered the statistical precision in the available studies. HRT is used to mitigate discomfort caused by decreased levels of circulating oestrogen and progesterone after menopause. Combined HRT includes both oestrogens and progesterone, and is recommended to women with an intact uterus, as it counteracts endometrial hyperplasia associated with oestrogen therapy. Oestrogen only HRT is recommended to women who have undergone hysterectomy. 16,17 The most commonly used OCs contain both oestrogen and progesterone. The often called 'mini pill' contains progesterone only, 18 and is recommended during breastfeeding as oestrogen reduces the amount of breast milk. 19 With the purpose of improving the knowledge of the relationship between HRT and OC exposure and risk of OAC, we conducted a systematic review and meta-analysis. Material a...

Hormonal and reproductive factors and risk of esophageal cancer in women: a meta-analysis

“…Women using sex hormones, such as HRT after menopause and OC, may be less susceptible to EC. A recent meta‐analysis of five independent studies has implicated that OC and HRT use seemed to reduce the risk of EAC . On the contrary, no significant association between OC and HRT use and the risk of EAC was found in our meta‐analysis of six individual publications.…”

Menopausal hormone therapy and the risk of esophageal and gastric cancer

“…Original studies examining MHT and risk of esophageal and gastric adenocarcinoma have typically been under‐powered, have mostly examined one or two cancers per study and arrived at inconsistent findings . However, meta‐analyses comparing ever‐users of MHT with non‐users have shown statistically significantly decreased relative risk estimates of esophageal adenocarcinoma, gastric adenocarcinoma and also of esophageal squamous cell carcinoma . We hypothesized that MHT decreases the risk of esophageal and gastric adenocarcinoma, but not of esophageal squamous cell carcinoma.…”

Hormonal and reproductive factors and risk of upper gastrointestinal cancers in men: A prospective cohort study within the UK Biobank

“…Similar to our study although, Lu et al found no significant relationship for increasing number of children fathered. 23 In women, although results from individual studies have been inconsistent, pooled analyses have found positive associations for menopause 31 and inverse associations for breastfeeding, 31,32 longer years of fertility 33 and HRT use, 31,33,34 providing some support that endogenous and exogenous oestrogen exposure may lower oesophageal and gastric cancer risk in women. The weak evidence of an association between frontal baldness and gastric cancer risk is difficult to interpret and requires confirmation.…”