The effect of estrogen vs. combined estrogen‐progestogen therapy on the risk of colorectal cancer

Abstract

Studies suggest that estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) may have different associations with colorectal cancer (CRC) risk, but data are conflicting. Prior meta-analyses did not distinguish between ET and EPT. We conducted a meta-analysis to summarize the relative risks (RR) of CRC due to ET versus EPT among peri-or postmenopausal women. From a total of 2,661 articles, four randomized controlled trials, eight cohort and eight case-control studies were included. Variables assessed included study characteristics, duration and recency of menopausal hormone therapy (HT) use, method of assessment of HT use, outcome definition and its ascertainment method. RRs were synthesized by random-effects models. We found that EPT ever use was associated with a decreased risk of CRC (RR 0.74, 95% CI 0.68-0.81), and so was ET ever use (RR 0.79, 95% CI 0.69-0.91). While current use of ET was associated with a significantly reduced risk of CRC (RR 0.70, 95% CI 0.57-0.85), former use was not (RR 0.86, 95%CI 0.67-1.11). Recency did not significantly modify the association between EPT and CRC risk. EPT former use was associated with a lower RR of CRC compared to ET former use (p 5 0.008) but no such difference was observed between EPT and ET current use (p 5 0.12). Overall, we found consistent evidence supporting the association between EPT and CRC risk reduction, regardless of recency. While literature for the association between ET and CRC risk is heterogeneous, our analyses suggest only current use of ET is associated with a decreased CRC risk.Menopausal hormone therapy (HT) is indicated for shortterm control of intolerable menopausal symptoms and it has a limited role in the treatment of osteoporosis for selected woman. While HT was found to increase the risks of venous thromboembolism, breast cancer and stroke, studies have also suggested that it may be associated with a reduced risk of colorectal cancer (CRC).1 Grodstein et al. conducted a meta-analysis of 18 observational studies that summarized the effect of HT on CRC risk, and showed an overall inverse association, with a pooled relative risk (RR) of 0.80 (95% CI 0.74-0.86).2 Another meta-analysis published by Nanda et al. revealed similar results.3 The explanation for the observed association has been controversial, however, because selective prescribing of HT to healthier subjects (i.e., healthy user bias) may have accounted for superior outcomes in the HT group. This concern was partly settled by the Women's Health Initiative (WHI) study, a large-scale randomized controlled trial (RCT), which found that the use of conjugated equine estrogens plus medroxyprogesterone acetate was associated with a reduction in CRC risk. 4 In contrast, one study did not find a significant association between the use of conjugated equine estrogen alone and CRC risk, although the small number of CRC cases may have limited its interpretation and generalizability. 5 In fact, the WHI study results were not directly comparable with previous observational studies an...

Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality

“…3,12,[19][20][21][22][23][24][25][26][27] In both a meta-analysis of eight such studies 27 and this meta-analysis incorporating 10 studies, a modest but statistically significant lower colorectal cancer incidence is associated with combined hormone therapy use. Such results agree with the current randomized clinical trial results regarding diagnosis rates but do not address the question of clinical relevance of the findings, since Abbreviation: SD, standard deviation.…”

“…1 However, during the intervention phase of the trial, there was a statistically significant 44% lower rate of colorectal cancer diagnoses in the estrogen plus progestin group, 2 a finding in agreement with the preponderance of observational studies. 3 Consequently, review articles, 4,5 position statements, 6-10 and executive summaries 11 of professional societies commonly listed reduction of colorectal cancer risk as a benefit of estrogen plus progestin use.…”

Colorectal Cancer Risk Associated with Hormone Use Varies by Expression of Estrogen Receptor-β

“…In a recent meta-analysis of 4 randomized controlled trials, 8 cohorts and 8 case-control studies, ever use of a combined estrogen-progestagen therapy was associated with a 26% decreased risk for colorectal cancer [OR, 0.74; 95% confidence interval (CI), 0.68-0.81] and a similar result was observed with ever use of estrogen monotherapy (OR, 0.79; 95% CI, 0.69-0.91; ref. 3). The results of a meta-analysis investigating the association between ever use of oral contraceptives and colorectal cancer risk indicated also an inverse relationship, with a risk reduction of 19% (OR, 0.81; 95% CI, 0.72-0.92; ref.…”

Survival Impact of Extracolorectal Malignancies in Colorectal Cancer Patients

“…In contrast, according to GLOBOCAN 2012, which compiled data on the cancer incidence and mortality estimates in 184 countries worldwide, the most common primary cancer site other than the colorectum in Asia was the lung, followed by the stomach, breast and liver [16] . Most notably, the [17][18][19] , whereas they promote the development and progression of breast cancer [20][21][22] , and this might explain the relatively low incidence of breast cancer in CRC patients. Although several reports from other Asian countries have demonstrated a high frequency of CRC in hepatocellular carcinoma patients [23,24] , the incidence of hepatocellular carcinoma was low in the present study, and we speculate that ethnic differences might have affected these distributions of EMs.…”