[Current and future medical treatment for endometriosis]
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by claude@2026-06, 2026-06-08
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This paper reviews current treatments for endometriosis and proposes inhibitor of apoptotic protein (IAP) inhibitors, such as parthenolide and SERMs, as novel therapeutic agents by targeting NF-κB activation and reducing inflammation.
Abstract
Endometriosis is a chronic, progressive inflammatory disease that occurs in approximately 10% of women of reproductive age, resulting in a decreased quality of life due to dysmenorrhea, chronic pain, and other problems. The primary treatment is pain control and fertility preservation, and while preserving ovarian function through drug therapy and surgery, assisted reproductive technology (ART), including in vitro fertilization (IVF), is also utilized. Hormonal therapies such as low-dose estrogen/progestin (LEP), progestins, and GnRH analogs are often the drug of choice. We presented that IAP (inhibitor of apoptotic protein) inhibitors can potentially be novel agents for treating endometriosis. Our studies using cultured cells derived from human endometriotic lesions and mouse models have revealed that inflammatory cytokines and antiapoptotic factors (IAPs) produced by peritoneal macrophages or endometriosis cells are crucial and that NF-κB (nuclear factor-kappa B) plays a central role in the pathogenesis of endometriosis. The high expression of IAPs in human endometriotic tissues, its facilitative role in ectopic survival, and the effect of IAPs on drug-resistant apoptosis of human endometriotic cells indicate its potential as a novel drug for IAP inhibitors. We found that the medicinal herb parthenolide and selective estrogen receptor modulators (SERM) can reduce lesions through NF-κB inhibition. Recently, new findings were obtained by non-invasive observation of early lesions using bioluminescence technology and by applying knockout mouse models. We will show the possibility of new therapeutic agents for endometriosis.
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抄録
子宮内膜症は生殖年齢女性の約10%に認められる慢性の進行性炎症疾患であり,月経困難症・骨盤痛などによるQOL低下が問題となる.症状の進行により,不妊の原因(排卵障害・卵管障害),妊娠後の産科合併症(早産・前期破水・前置胎盤など)が増加することに加え,稀ではあるが卵巣がんへの進展を起こすことも知られている.少子化対策・女性活躍推進が叫ばれる昨今の社会情勢において重要視されている疾患の1つである.治療の基本は,疼痛抑制と妊孕性温存であり,薬物療法と手術療法により卵巣機能の温存を図りながら,体外受精をはじめとする生殖補助医療(ART)を駆使する.薬物療法は,低用量ピル(低用量エストロゲン・プロゲスチン配合薬:LEP),黄体ホルモン,GnRHアナログなどのホルモン療法が選択されることが多い.これまで,ヒト子宮内膜症病変組織由来の培養細胞や子宮内膜症モデルマウスを用いて研究をすすめ,腹腔マクロファージや子宮内膜症細胞が産生する炎症性サイトカインや抗アポトーシス因子(IAP)が病態形成に重要であること,そこではNF-κBが中心的役割を有することを明らかにした.ヒト子宮内膜症組織ではIAP発現が高く異所性生存に促進的に関与すること,IAPがヒト子宮内膜症細胞の薬剤抵抗性アポトーシスに作用することから,IAP阻害薬の新規薬剤としての可能性を示した.さらには,薬用ハーブ・パルテノライドや選択的エストロゲン受容体調節剤が,NF-κB阻害により病変を縮小させることを示した.最近では,生物発光技術による非侵襲的な初期病変の観察や,ノックアウトマウスを応用したモデルマウスにより新知見を得た.本稿では,これまでの研究成果を掲示し,新たな子宮内膜症治療薬の可能性について考察する.
© 2024 公益社団法人 日本薬理学会
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Condition tags
endometriosisdysmenorrhea
MeSH descriptors
Endometriosis
Endometriosis
Endometriosis
Endometriosis
Endometriosis
Endometriosis
Endometriosis
Endometriosis
Animals
Animals
Animals
Animals
Animals
Animals
Animals
Female
Female
Female
Female
Female
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- europepmc
- last seen: 2026-06-11T06:19:48.454388+00:00
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- last seen: 2026-05-21T00:32:12.502489+00:00
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