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The establishment of the safe hormone replacement therapy that can reduce arteriosclerosis risk

Research Project

Project/Area Number 21K09546
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Ito Fumitake  京都府立医科大学, 医学(系)研究科(研究院), 講師 (60756849)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsホルモン補充療法 / 動脈硬化 / エストロゲン / en face解析 / aortic root解析 / エストラジオール / エクイリン / 接着分子 / イソフラボン / 接着因子 / プロゲストーゲン
Outline of Research at the Start

当領域においてステロイドホルモンによる動脈硬化病変への影響を検証したin vivoでの基礎研究はこれまでに報告がないが、研究代表者らはモデルマウスを用いたin vivoで評価する系を確立させることに成功した。一方で、エストロゲン様物質であるイソフラボンの動脈硬化に対する影響を基礎的実験により明らかにした報告はこれまでにない。本研究により各種エストロゲンおよびエストロゲン様物質による動脈硬化リスクへの影響に関して基礎的データの蓄積がなされその機序が解明されれば、より安全なHRTの確立に寄与することが考えられる。

Outline of Final Research Achievements

In this study, in vivo experiments were conducted to examine the actual risk of atherosclerosis induced by E2 and Eq used in hormone replacement therapy. E2 and Eq were subcutaneously administered. Aorta and its branches were examined for atherosclerotic lesions using en face analysis and aortic root analysis. The results showed that E2 showed an inhibitory effect on atherosclerosis compared to the control group, but the effect of Eq was weaker than that of E2, although a certain degree of inhibition was observed.

Academic Significance and Societal Importance of the Research Achievements

本研究では、EqおよびE2の経皮投与は脂質プロファイルを変化させることなくアテローム性動脈硬化病変の形成を阻害し、E2の方がより優れた効果を示した。これらの結果は、Eqを含むCEEよりもE2の短期および長期の使用が、動脈硬化の発生に対してより優れた抑制効果を有する可能性を示唆している。しかしながら、ホルモン補充療法に併用される酢酸メドロキシプロゲステロン(MPA)および天然型のP4を含むプロゲスチンの動脈硬化発症に対する効果は未解明なためさらに詳しい検討が必要であり、動脈硬化予防のための最適なHRTレジメンを解明するためのさらなる研究が必要である可能性を示した。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (15 results)

All 2023 2022 2021 2020

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 4 results) Book (1 results)

  • [Journal Article] Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis2023

    • Author(s)
      Shimura K, Tarumi Y, Fujii M, Ogawa K, Maeda E, Tanaka Y, Okimura H, Kataoka H, Takaoka O, Ito F, Koshiba A, Khan KN, Kusuki I, Kitawaki J, Mori T.
    • Journal Title

      Reprod Sci.

      Volume: 30 Issue: 4 Pages: 1094-1102

    • DOI

      10.1007/s43032-022-01089-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Postoperative Pregnancy Outcomes Following Laparoscopic Surgical Management in Women with Stage III/IV Endometriosis: A Single-Center Follow-Up Study2023

    • Author(s)
      Fujii M, Koshiba A, Ito F, Kusuki I, Kitawaki J, Mori T.
    • Journal Title

      Gynecol Minim Invasive Ther

      Volume: 12 Issue: 3 Pages: 153-160

    • DOI

      10.4103/gmit.gmit_132_22

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepcidin as a key regulator of iron homeostasis triggers inflammatory features in the normal endometrium2023

    • Author(s)
      Izumi Yuko、Kataoka Hisashi、Koshiba Akemi、Ito Fumitake、Tanaka Yukiko、Takaoka Osamu、Maeda Eiko、Okimura Hiroyuki、Sugahara Takuya、Tarumi Yosuke、Shimura Koki、Khan Khaleque N.、Kusuki Izumi、Mori Taisuke
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 209 Pages: 191-201

    • DOI

      10.1016/j.freeradbiomed.2023.10.402

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dienogest does not augment the gene expression of adhesion molecules, MCP-1, and monocyte adherence in human endothelial cells2023

    • Author(s)
      Tahara N, Ito F, Kawamata M, Otani M, Mori T.
    • Journal Title

      Gynecological Endocrinology

      Volume: 40 Issue: 1 Pages: 2270621-2270621

    • DOI

      10.1080/09513590.2023.2270621

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in the proportion of regulatory T cell subpopulations during menstrual cycle and early pregnancy2022

    • Author(s)
      Okimura H, Tanaka Y, Fujii M, Shimura K, Maeda E, Ito F, Khan KN, Nakamura Y, Mori T, Kitawaki J.
    • Journal Title

      Am J Reprod Immunol.

      Volume: 88 Issue: 6

    • DOI

      10.1111/aji.13636

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis2022

    • Author(s)
      Tarumi Y, Mori T, Shimura K, Izumi Y, Okimura H, Kataoka H, Kokabu T, Ito F, Koshiba A, Khan KN, Kusuki I, Kitawaki J.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 107 Issue: 6 Pages: 1552-1559

    • DOI

      10.1210/clinem/dgac118

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Robot-assisted laparoscopic hysterectomy for early-stage endometrial cancer with massive uterine leiomyomas: A case report2022

    • Author(s)
      Kakibuchi A, Ito F, Kokabu T, Okimura H, Takaoka O, Mori T.
    • Journal Title

      Int J Surg Case Rep

      Volume: 97 Pages: 107473-107473

    • DOI

      10.1016/j.ijscr.2022.107473

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary ovarian leiomyoma associated with multiple uterine leiomyomas2021

    • Author(s)
      Ito Fumitake、Kitamura Yoshihiro、Kokabu Tetsuya、Mori Taisuke、Kusuki Izumi、Kitawaki Jo
    • Journal Title

      Gynecology and Minimally Invasive Therapy

      Volume: 10 Issue: 1 Pages: 50-50

    • DOI

      10.4103/gmit.gmit_97_19

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Severe coronavirus disease pneumonia in a pregnant woman at 25 weeks' gestation: A case report2021

    • Author(s)
      Waratani Miyoko、Ito Fumitake、Tanaka Yukiko、Mabuchi Aki、Mori Taisuke、Kitawaki Jo
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 47 Issue: 4 Pages: 1583-1588

    • DOI

      10.1111/jog.14701

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin‐9 produced by helper T cells stimulates interleukin‐8 expression in endometriosis2020

    • Author(s)
      Tarumi Yosuke、Mori Taisuke、Okimura Hiroyuki、Maeda Eiko、Tanaka Yukiko、Kataoka Hisashi、Ito Fumitake、Koshiba Akemi、Kusuki Izumi、Kitawaki Jo
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: - Issue: 3

    • DOI

      10.1111/aji.13380

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Daidzein-rich isoflavone aglycones inhibit HSD17beta 1 in endometriosis.2021

    • Author(s)
      Takoka O, Mori T, Shimura K, Ogawa K, Okimura H, Kataoka H, Ito F, Koshiba A, Kusuki I, Kitawaki J.
    • Organizer
      73th Annual Congress of Japan Society of Obstetrics and Gynecology.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Low expression of progesterone receptor acts as a predictive factor for recurrence of ovarian endometrioma and concurrence of deep endometriosis.2021

    • Author(s)
      Tarumi Y, Mori T, Koshiba A, Shimura K, Okimura H, Kataoka H, Ito F, Khan KN, Kusuki I, Kitawaki J.
    • Organizer
      73th Annual Congress of Japan Society of Obstetrics and Gynecology.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Local variation of regulatory T cells during menstrual cycle in endometriosis.2021

    • Author(s)
      Fujii M, Tanaka Y, Okimura H, Sugahara T, Maeda E, Kataoka H, Ito F, Koshiba A, Khan KN, Mori T, Kusuki I, Kitawaki J.
    • Organizer
      73th Annual Congress of Japan Society of Obstetrics and Gynecology.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of laparoscopic surgery with complete excision of deep endometriosis on pregnancy rate of non-assites reproductive technology.2021

    • Author(s)
      Fujii M, Koshiba A, Shimura K, Otani M, Ito F, Mori T, Kusuki I, Kitawaki J.
    • Organizer
      22th Annual Congress of the Asia Pacific Association for Gynecologic Endoscopy and Minimally Invasive Therapy (APAGE 2021).
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Book] §20-30 早発閉経. 1252専門家による 私の治療 [2021-22年度版].2021

    • Author(s)
      伊藤文武, 北脇 城.
    • Total Pages
      2
    • Publisher
      日本医事新報社
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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