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Cited by 183Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsVenous Thromboembolism Diagnosis and Management

Oral vs Transdermal Estrogen Therapy and Vascular Events: A Systematic Review and Meta-Analysis

Mohammed, Khaled, Abu Dabrh, Abd Moain, Benkhadra, Khalid, Al Nofal, Alaa, Carranza Leon, Barbara G., Prokop, Larry J., Montori, Victor M., Faubion, Stephanie S. +1 more·2015·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2015-2237
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Abstract

BACKGROUND: Menopausal hormone therapy is widely used to alleviate climacteric symptoms but may increase the risk of venous and arterial vascular events. OBJECTIVE: The objective was to synthesize the evidence about the risk of vascular events in postmenopausal women who use oral estrogen therapy (ET) and transdermal ET. METHODS: We searched bibliographical databases through August 2013 for longitudinal comparative studies that enrolled postmenopausal women using either oral or transdermal ET and reported the outcomes of interest: venous thromboembolism (VTE), pulmonary embolism, deep venous thrombosis (DVT), myocardial infarction (MI), and stroke. Two reviewers independently selected and appraised studies. Outcomes were pooled using random effects meta-analysis and were reported as risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included 15 observational studies at moderate risk of bias with follow-up of 3 to 20.25 years. When compared to transdermal ET, oral ET was associated with increased risk of a first episode of VTE (RR, 1.63; 95% CI, 1.40-1.90; I(2) = 53%), DVT (RR, 2.09; 95% CI, 1.35-3.23; I(2) = 0 %), and possibly stroke (RR, 1.24; 95% CI, 1.03-1.48; a single case-controlled study), but not MI (RR, 1.17; 95% CI, 0.80-1.71; I(2) = 74%). CONCLUSION: Observational evidence warranting low confidence suggests that compared to transdermal ET, oral ET may be associated with increased risk of VTE and DVT, but not MI.

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  • The increased risk of estrogen-associated thrombosis depends on both the dose and the mode of delivery of the hormone.

    “The increased risk is dependent both on the dose and well as the mode of delivery of the hormone, and studies identify alterations in numerous aspects of the hemostatic and fibrinolytic pathways that contribute to the generation of a prothrombotic milieu.”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [89]

  • Oral estrogen therapy is associated with a higher risk of first episode of VTE (RR, 1.63; 95% CI, 1.40-1.90) and deep venous thrombosis (RR, 2.09; 95% CI, 1.35-3.23) compared to transdermal estrogen therapy in postmenopausal women.

    “Finally, a meta-analysis of 15 observational studies showed that oral estrogen therapy was associated with a higher risk of first episode of VTE (RR, 1.63; 95% CI, 1.40–1.90) and deep venous thrombosis (DVT) (RR, 2.09; 95% CI, 1.35–3.23) when compared to transdermal estrogen therapy in post menopausal women.”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [89]

  • The level of evidence for the comparison of oral versus transdermal estrogen and VTE/DVT risk is low because the studies were observational and randomized control studies are not available.

    “The level of evidence is low, since these were only observational studies and randomized control studies are not available [89].”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [89]

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Authors
Mohammed, K., Abu Dabrh, A. M., Benkhadra, K., Al Nofal, A., Carranza Leon, B. G., Prokop, L. J., Montori, V. M., Faubion, S. S., & Murad, M. H.
Affiliations
Mayo Clinic (US)
Corresponding author
Murad, Mohammad Hassan
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2015-11
Volume
100
Issue
11
Pages
4012-4020
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2015-2237
OpenAlex
W2102826076
Cited by
183
References
29
Citations by year
2026: 22 · 2025: 19 · 2024: 15 · 2023: 15 · 2022: 16 · 2021: 14 · 2020: 22 · 2019: 12 · 2018: 21 · 2017: 17 · 2016: 10
FWCI
13.87
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
Keywords
hormone replacement therapy, oral estrogen therapy, vascular events, venous thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, postmenopausal women
MeSH terms
Administration, Oral, Female, Humans, Menopause, Risk Factors, Estrogen Replacement Therapy, Evidence-Based Medicine, Venous Thrombosis, Stroke, Venous Thromboembolism, Transdermal Patch, Observational Studies as Topic

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