ArticleResearch and practice in thrombosis and haemostasis2021
Bias in animal studies of estrogen effects on cardiovascular disease: A systematic review and meta-analysis.
Article in Research and practice in thrombosis and haemostasis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.
- Systematic review and meta-analysis of the antidepressant-like effects of ginsenosides in animal models: comparative behavioral profiles and exploratory dose-stratified analysis.Frontiers in pharmacology · 2026Pooled it
- Evaluation of TyG index and TG/HDL-C ratio in HBeAg negative chronic hepatitis B infected patients.Biomolecules & biomedicine · 2023Article
- Does publication bias explain the divergent findings on menopausal hormone therapy and cardioprotection in the literature?Research and practice in thrombosis and haemostasis · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRandomized controlled trials on menopausal hormone therapy in humans have not confirmed the benefit of estrogens on cardiovascular disease found in animal studies. Flawed methodology or publication bias in animal studies may explain the dicrepancy.
objectivesThe aim of this study was to investigate whether publication of the randomized controlled trials Heart and Estrogen/Progestin Replacement Study and Women's Health Initiative influenced study authors' assessment of research findings (confirmation bias) as well as to investigate publication bias and small-study effects in animal studies of estrogen effects on atherosclerosis.
methodsThe data source for this study was PubMed from inception to 2018. We selected animal studies with cardiovascular outcomes comparing 17-β-estradiol, its natural metabolites, or conjugated equine estrogen with control. Qualitative data were extracted on authors' conclusions about estrogen effects on cardiovascular disease, as well as quantitative data for atherosclerosis outcomes. Fixed- and random-effects meta-analyses were used. Publication bias/small-study effects were assessed using funnel plots and Egger's regression. Trim-and-fill plots and extrapolation from Egger's regression were used to adjust for publication bias. The main outcomes and measures were the primary study authors' interpretation of their own results, and estrogen effects on cardiovascular disease in general before and after publication of the Women's health Initiative study (2003). The effects of estrogens on atherosclerosis were measured as standardized mean difference between intervention and control.
resultsOf 1925 studies retrieved, 360 were eligible for analyses. Study-specific statements concluded that estrogens were protective against cardiovascular disease in 75% of studies before 2003 and 78% after, but the percentage of general statements about estrogens being cardioprotective changed from 70% to 40%. Meta-analyses showed less atherosclerosis in estrogen-treated animals. Extremely skewed funnel plots and
conclusionsWe found substantial evidence of publication bias but not of confirmation bias. Publication bias and flawed small studies may partly explain why findings differ between animal studies and clinical trials on the effect of estrogens on cardiovascular disease.
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Registered trials
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