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Postmenopausal hormone replacement therapy for prevention of coronary heart disease

Research Project

Project/Area Number 14571567
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKOCHI MEDICAL SCHOOL

Principal Investigator

WAKATSUKI Akihiko  Kochi Medical School, Department of Obstetrics and Gynecology, Associate professor, 医学部附属病院・周産母子センター, 助教授 (90191717)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordspostmenopausal women / transdermal HRT / coronary heart disease / vascular inflammation / エストロゲン補充 / 中性脂肪 / LDLサイズ
Research Abstract

(Objectives) Postmenopausal hormorie replacement therapy(HRT) decreases the incidence of coronary heart disease(CHD). According to the recent studies, however, HRT increased the risk of CHD in postmenopausal women. We previously demonstrated that oral HRT increases vascular inflammatory markers such as C-reactive protein(CRP) concentrations. In the present study, we evaluated whether oral HRT have a pro-inflammatory effect and investigated the effects of transdermal HRT on vascular inflammatory markers.
(Methods and Results) Postmenopausal women received no treatment or were treated with 0.625mg oral conjugated equine estrogen daily or with transdermal estradiol(25μg/day,n=15) for 3 months. Oral ERT significantly increased plasma concentrations of CRP, serum amyloid A protein(SAA), and matrix metalloproteinase(MMP)-3, but significantly decreased tissue inhibitor of MMP(TIMP)-1 concentrations by 8.6%. In contrast, transdermal ERT significantly decreased CRP concentrations and tended to increase TIMP-1 concentrations. Oral ERT significantly, decreased p-selectin concentrations, but the concentrations of intercellular adhesion molecule(ICAM-1) and vascular cell adhesion molecule(VCAM-1) did not change significantly. Transdermal ERT, however, significantly decreased all cell adhesion molecule concentrations.
(Conclusion) Oral HRT may have a pro-inflammatory effect by increasing vascular inflammatory markers. Oral HRT-induced increases in inflammatory markers and imbalances between MMP and TIMP-1 might be reversed by transdermal administration of estrogen. Because transdermally administered estrogen decreased cell adhesion molecule concentrations, the anti-inflammatory effect of transdermal HRT may actually be responsible for the favorable effect of estrogen on cell adhesion molecule, concentrations in postmenopausal women.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T: "Effect of medroxyprogesterone acetate on vascular inflammatory markers in postmenopausal women receiving estrogen."Circulation. 105. 1436-1439 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Ogawa Y, Saibara T, Fukaya T: "Size and oxidative susceptibility of low-density lipoprotein particles in breast cancer patients with tamoxifen-induced fatty liver."J Clin Endocrinol Metab. 87. 3676-3681 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T: "Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women."Circulation. 106. 1771-1776 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T: "Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women."Circulation. 105. 1436-1439 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T: "The antiinflammatory properties of medroxyprogesterone acetate."Circulation. 106. e185 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T: "Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance"Circulation. 107. e197 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T: "Effect of transdermal estradiol and oral conjugated equine estrogen on C-reactive protein in retinoid-placebo trial in healthy women."Circulation. 107. e127-e128 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Ikenoue N, Shinohara K, Watanabe K, Fukaya T: "Different effects of oral and transdermal estrogen replacement therapy on matrix metalloproteinase and their inhibitor in postmenopausal women."Arterioscler Thromb Vasc Biol. 23. 1948-1949 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Shinohara K, Watanabe K, Fukaya T: "Effect of lower dose of oral conjugated equine estrogen on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women."Circulation. 108. 808 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A: "Postmenopausal hormone replacement therapy and cardiovascular disease."Progress in Hormone Replacement Therapy Research. Nova Science Publishers, USA.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T.: "Effect of medroxyprogesterone acetate on vascular inflammatory markers in postmenopausal women receiving estrogen."Circulation. 105. 1436-1439 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Ogawa Y, Saibara T, Okatani Y, Fukaya T.: "Size and oxidative susceptibility of low-density lipoprotein particles in breast cancer patients with tamoxifen-induced fatty liver."J Gin Endocrinol Metab.. 87. 3676-3681 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T.: "Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women."Circulation. 106. 1771-1776 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T.: "Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women."Circulation. 105. 1436-1439 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T.: "The antiinflammatory properties of medroxyprogesterone acetate."Circulation. 106. e185 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T.: "Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance."Circulation. 107. e197 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T: "Effect of transdermal estradiol and oral conjugated equine estrogen on C-reactive protein in retinoid-placebo trial in healthy women."Circulation. 107. e127-e128 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Ikenoue N, Shinohara K, Watanabe K, Fukaya T: "Different effect of oral and transdermal estrogen replacement therapy on matrix metalloproteinase and their inhibitor in postmenopausal women."Arterioscler Thromb Base Biol. 23. 1948-1949 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, Shinohara K, Watanabe K, Fukaya T.: "Effect of lower dose of oral conjugated equine estrogen on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women."Circulation. 108. 808-813 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A.: "Postmenopausal hormone replacement therapy and cardiovascular disease.(Progress in Hormone Replacement Therapy Research)"Nova Science Publishers, USA(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T: "Effect of transdermal estradiol and oral conjugated equine estrogen on C-reactive protein in retinoid-placebo trial in healthy women"Circulation. 107. 127-128 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wakatsuki A, Ikenoue N, Shinohara K, Watanabe K, Fukaya T: "Different effects of oral and transdermal estrogen replacement therapy on matrix metalloproteinase and their inhibitor in psotmenopausal women"Arterioscler Thromb Vasc Biol. 23. 1948-1949 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wakatsuki A, Okatani Y, Ikenoue N, et al.: "Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women"Circulation. 106. 1771-1776 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wakatsuki A, Okatani Y, Fukaya T: "Effect of transdermal estradiol and oral conjugated equine estrogen on C-reactive protein in retinoid-placebo trial in healthy women"Circulation. (in press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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