後期発症のレバー遺伝光神経病と前立腺がんの抗アンドロゲン薬:因果関係はあるのか?
Giulia Amore1,2, Michele Carbonelli3, Diego D'Angeli3
1Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy.
Frontiers in neurology
|September 2, 2025
まとめ
アンドロゲン欠乏療法 (ADT) は,前立腺がんの男性において,遅発のレバー遺伝視神経病 (LHON) を引き起こす可能性があります. このホルモンの不均衡,特に低エストロゲンのレベルは,ミトコンドリアDNA複製数の減少と視力喪失につながる可能性があります.
科学分野:
- 眼科について
- 遺伝学
- 内分泌学
背景:
- レベルの遺伝性視神経病 (LHON) は,母性遺伝によるミトコンドリアDNA疾患で,典型的には若い男性に影響を与え,おそらくエストロゲンによる女性の保護効果を示している.
- 遅発のLHONはしばしば毒性被曝と関連しているが,これらの要因とは無関係な症例はあまり理解されていない.
研究 の 目的:
- 前立腺がんの高齢者における LHON の2つの異常な症例を報告します
- アンドロゲン欠乏療法 (ADT) がこれらの患者でLHONを誘発する可能性を調査する.
主な方法:
- 遅発LHONの2人の患者の詳細な臨床症例報告
- ホルモンプロファイル (ゴナドトロピン,エストロゲン,アンドロゲン) とミトコンドリアDNA (mtDNA) の複製数の分析
主要な成果:
- 両方の患者は,進行した前立腺がんに対するADT (エンザルタミドとルプロリド) を開始した後,LHONを発症しました.
- エストロゲンとアンドロゲンの血清濃度が非常に低く,ADTと一致していました.
- コントロール群と比較して,mtDNAの複製数が著しく減少した.
結論:
- ADTは,ホルモンのバランス (エストロゲン-アンドロゲン比) を変化させ,潜在的にmtDNAの複製数を減らすことで,感受性の高い個体で遅発のLHONを引き起こす可能性があります.
- これは,LHONの病原性におけるホルモン状態とミトコンドリア機能の複雑な相互作用を示唆する.
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