Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women

Kwang Kon Koh, Dong Kyu Jin, Seong Hee Yang, Seon Kyu Lee, Hee Young Hwang, Moon Ho Kang, Wan Kim, Dae Sung Kim, In Suck Choi, Eak Kyun Shin

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Background - Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. Methods and Results - In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). Conclusions - CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.

Original languageEnglish (US)
Pages (from-to)1961-1966
Number of pages6
JournalCirculation
Volume103
Issue number15
DOIs
StatePublished - Apr 17 2001
Externally publishedYes

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Conjugated (USP) Estrogens
Progestins
Blood Vessels
Medroxyprogesterone Acetate
Analysis of Variance
Progesterone
Estrogens
E-Selectin
Vascular Cell Adhesion Molecule-1
Thromboplastin
Intercellular Adhesion Molecule-1
Progesterone Congeners
Therapeutics
Antigens
Endothelium-Dependent Relaxing Factors
Chemokine CCL2
Plasminogen Activator Inhibitor 1
Hyperemia
Fibrinolysis
Hemostasis

Keywords

  • Atherosclerosis
  • Cell adhesion molecules
  • Endothelium
  • Fibrinolysis
  • Proteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women. / Koh, Kwang Kon; Jin, Dong Kyu; Yang, Seong Hee; Lee, Seon Kyu; Hwang, Hee Young; Kang, Moon Ho; Kim, Wan; Kim, Dae Sung; Choi, In Suck; Shin, Eak Kyun.

In: Circulation, Vol. 103, No. 15, 17.04.2001, p. 1961-1966.

Research output: Contribution to journalArticle

Koh, KK, Jin, DK, Yang, SH, Lee, SK, Hwang, HY, Kang, MH, Kim, W, Kim, DS, Choi, IS & Shin, EK 2001, 'Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women', Circulation, vol. 103, no. 15, pp. 1961-1966. https://doi.org/10.1161/01.CIR.103.15.1961
Koh, Kwang Kon ; Jin, Dong Kyu ; Yang, Seong Hee ; Lee, Seon Kyu ; Hwang, Hee Young ; Kang, Moon Ho ; Kim, Wan ; Kim, Dae Sung ; Choi, In Suck ; Shin, Eak Kyun. / Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women. In: Circulation. 2001 ; Vol. 103, No. 15. pp. 1961-1966.
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abstract = "Background - Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. Methods and Results - In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). Conclusions - CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.",
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AU - Jin, Dong Kyu

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AU - Lee, Seon Kyu

AU - Hwang, Hee Young

AU - Kang, Moon Ho

AU - Kim, Wan

AU - Kim, Dae Sung

AU - Choi, In Suck

AU - Shin, Eak Kyun

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N2 - Background - Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. Methods and Results - In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). Conclusions - CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.

AB - Background - Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. Methods and Results - In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). Conclusions - CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.

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