Oral vs transdermal estrogen therapy and vascular events: A systematic review and meta-analysis

Khaled Mohammed, Abd Moain Abu Dabrh, Khalid Benkhadra, Alaa Al Nofal, Barbara G. Carranza Leon, Larry J. Prokop, Victor Manuel Montori, Stephanie S. Faubion, Mohammad H Murad

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 metaanalysis 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; I2 = 53%), DVT (RR, 2.09; 95% CI, 1.35-3.23; I2 = 0 %), andpossibly stroke (RR, 1.24;95%CI, 1.03-1.48; a single case-controlled study), but notMI(RR, 1.17; 95% CI, 0.80-1.71; I2 = 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.

Original languageEnglish (US)
Pages (from-to)4012-4020
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number11
DOIs
StatePublished - Nov 1 2015

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Blood Vessels
Meta-Analysis
Estrogens
Odds Ratio
Confidence Intervals
Venous Thromboembolism
Venous Thrombosis
Therapeutics
Stroke
Myocardial Infarction
Pulmonary Embolism
Observational Studies
Longitudinal Studies
Databases
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

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 Manuel; Faubion, Stephanie S.; Murad, Mohammad H.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 11, 01.11.2015, p. 4012-4020.

Research output: Contribution to journalArticle

Mohammed, Khaled ; Abu Dabrh, Abd Moain ; Benkhadra, Khalid ; Al Nofal, Alaa ; Carranza Leon, Barbara G. ; Prokop, Larry J. ; Montori, Victor Manuel ; Faubion, Stephanie S. ; Murad, Mohammad H. / Oral vs transdermal estrogen therapy and vascular events : A systematic review and meta-analysis. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 11. pp. 4012-4020.
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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 metaanalysis 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; I2 = 53{\%}), DVT (RR, 2.09; 95{\%} CI, 1.35-3.23; I2 = 0 {\%}), andpossibly stroke (RR, 1.24;95{\%}CI, 1.03-1.48; a single case-controlled study), but notMI(RR, 1.17; 95{\%} CI, 0.80-1.71; I2 = 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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T2 - A systematic review and meta-analysis

AU - Mohammed, Khaled

AU - Abu Dabrh, Abd Moain

AU - Benkhadra, Khalid

AU - Al Nofal, Alaa

AU - Carranza Leon, Barbara G.

AU - Prokop, Larry J.

AU - Montori, Victor Manuel

AU - Faubion, Stephanie S.

AU - Murad, Mohammad H

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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 metaanalysis 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; I2 = 53%), DVT (RR, 2.09; 95% CI, 1.35-3.23; I2 = 0 %), andpossibly stroke (RR, 1.24;95%CI, 1.03-1.48; a single case-controlled study), but notMI(RR, 1.17; 95% CI, 0.80-1.71; I2 = 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.

AB - 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 metaanalysis 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; I2 = 53%), DVT (RR, 2.09; 95% CI, 1.35-3.23; I2 = 0 %), andpossibly stroke (RR, 1.24;95%CI, 1.03-1.48; a single case-controlled study), but notMI(RR, 1.17; 95% CI, 0.80-1.71; I2 = 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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