Colorectal Cancer Incidence and Postmenopausal Hormone Use by Type, Recency, and Duration in Cancer Prevention Study II

Hildebrand, Janet S.; Jacobs, Eric J.; Campbell, Peter T.; McCullough, Marjorie L.; Teras, Lauren R.; Thun, Michael J.; Gapstur, Susan M.

doi:10.1158/1055-9965.epi-09-0596

Cited by 40 publications

(38 citation statements)

References 39 publications

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“…1). 4,5,13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Figure 2 shows the RR estimates reported by individual studies as well as the random effects pooled estimates for both ET and EPT. The pooled RRs of CRC were 0.79 (0.69-0.91) for ET ever use and 0.74 (0.68-0.81) for EPT ever use.…”

Section: Resultsmentioning

confidence: 99%

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

Lin

Cheung

Lai

et al. 2011

Intl Journal of Cancer

151

104

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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...

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Section: Resultsmentioning

confidence: 99%

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

Lin

Cheung

Lai

et al. 2011

Intl Journal of Cancer

151

104

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality

Simon

Chlebowski

Wactawski‐Wende

et al. 2012

JCO

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A B S T R A C T PurposeDuring the intervention phase in the Women's Health Initiative (WHI) clinical trial, use of estrogen plus progestin reduced the colorectal cancer diagnosis rate, but the cancers were found at a substantially higher stage. To assess the clinical relevance of the findings, analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up. Patients and MethodsThe WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were randomly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n ϭ 8,506) or matching placebo (n ϭ 8,102). Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed. ResultsAfter a mean of 5.6 years (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1 years) of total follow-up, fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group (diagnoses/year, 0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P ϭ .014). Bowel screening examinations were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (50.5% v 28.6%; P Ͻ .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P ϭ .003). Although not statistically significant, there was a higher number of colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths; 0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P ϭ .320). ConclusionThe findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer.

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“…Specifically, female predominance and a diagnosis at old age have been observed in proximal colon cancer cases, while men have demonstrated a predominance of distal colon cancer. This evidence suggests that sex hormones may play a role in the pathogenic pathways of colorectal cancer and via subtypes, but whether this role is protective or not is controversial [3][4][5][6][7][8][9][10]. Interestingly, some studies have found positive associations between endogenous hormones and risk of colorectal adenocarcinoma [11,12].…”

Section: Introductionmentioning

confidence: 99%

Increased risk of colorectal cancer in patients diagnosed with breast cancer in women

Segelman

Nordgren

et al. 2016

Cancer Epidemiology

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Colorectal Cancer Incidence and Postmenopausal Hormone Use by Type, Recency, and Duration in Cancer Prevention Study II

Cited by 40 publications

References 39 publications

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

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

Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality

Increased risk of colorectal cancer in patients diagnosed with breast cancer in women

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