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

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 501 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 11 vs. no HT prescriptions, 0.68, 95% CI 0.53-0.88; p 5 0.004), gastric cancer (0.75, 0.54-1.05; p 5 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 5 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 HTassociated increased risk of breast cancer.Although the use of certain types of hormone therapy (HT) for the menopause has been associated with increased risk of cancers of the reproductive tract, including breast, ovary and endometrium, 1,2 there is also evidence for a reduced risk of colorectal cancer in HT users. [3][4][5][6][7] However it is unclear whether the association with colorectal cancer differs by HT type or pattern of use, or by cancer site. [8][9][10] Epidemiological evidence for an association between HT use and risk of the less common cancers of the gastrointestinal tract is limited, with most published results showing non-significant reductions in risk in HT users both for oesophageal cancer [11][12][13][14] and for gastric cancer. 12,13,[15][16][17] We report here on the relation between prospectively recorded prescribing information for HT and the subsequent incidence of cancers of the oesophagus, stomach and colorectum in the UK General Practice Research Database (GPRD) cohort. We also report the results of meta-analyses combining our findings with other published data on the relation between HT use and the risk of each of the three gastrointestinal cancers.

Menopausal hormone therapy and risks of colorectal adenomas and cancers in the French E3N prospective cohort: true associations or bias?

“…Our findings of an inverse association between MHT use and cancer risk that was restricted to estrogens alone were similar to some [12,22,25,46] but not all [15,21,47] observational studies, and were not in line with results of the WHI trial [6,9]. Recent meta-analyses summarized the available evidence regarding colorectal cancer risk and MHT use, including type of MHT [16,17]. They concluded to the absence of a significant heterogeneity between estrogens used alone or with a progestagen, but did not compare oral and transdermal estrogens [16,17]; results regarding estrogens alone were heterogeneous across studies [16].…”

“…Recent meta-analyses summarized the available evidence regarding colorectal cancer risk and MHT use, including type of MHT [16,17]. They concluded to the absence of a significant heterogeneity between estrogens used alone or with a progestagen, but did not compare oral and transdermal estrogens [16,17]; results regarding estrogens alone were heterogeneous across studies [16]. One meta-analysis described associations by site; they were similar for the colon and rectal sites but no data were available regarding left versus right colon [17].…”

“…Among the other recent cohort studies, one observed a significant inverse association, but only with use of estrogens alone [12], another did not find any association with estrogens or estrogens combined with a progestagen [13] and two studies observed an inverse association with use of both estrogens alone and estrogens combined with a progestagen [14,15]. Finally, two recent meta-analyses reported a significantly decreased risk of colorectal cancer associated with both estrogens alone and estrogens combined with progestagens [16,17]. Results concerning the effect of the route of administration of estrogens [13,[18][19][20][21][22] or the site of the tumour [12,13,[23][24][25] are also conflicting.…”

Sex and Gender Differences in Gastroesophageal Reflux Disease

“…120 In a metaanalysis, risks for HRT use vs. never use of HRT significantly decreased for esophageal cancers (RR, 0.68; 95% CI, 0.55-0.84; P < 0.001) (Table). 121 However, a population-based retrospective cohort study for men who were exposed to quite a lot of estrogen has shown that there is no reduction in the risk of EAC by estrogen treatment. 110 The role of estrogen as an anti-inflammatory agent remains uncertain.…”

Overexpression of ERα inhibits proliferation and invasion of MKN28 gastric cancer cells by suppressing β-catenin

“…Furthermore, men who have been treated with estrogen for prostate cancer also have a decreased risk. In a meta-analyses, risks for ever vs. never use of hormone treatment (HT) were significantly reduced for gastric cancer (RR 0.78, confidence interval (CI) 0.65-0.94; P= 0.008) (17). A nested case-control study of hormone replacement therapy (HRT) demonstrated that a greater than 50% reduced risk of gastric adenocarcinoma was found among users of HRT compared to nonusers [odds ratio (OR), 0.48, 95% CI 0.29-0.79] (18).…”