子宮内膜症に対する薬物治療の現状と未来.

細川 雅代; 谷口 文紀

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 noninvasive observation of early lesions using bioluminescence technology and by applying knockout mouse models. We will show the possibility of new therapeutic agents for endometriosis.

SELECTIVE estrogen receptor modulators; NF-kappa B; CHILDBEARING age; PERITONEAL macrophages; FERTILITY preservation

Folia Pharmacologica Japonica, 2024, Vol 159, Issue 6, p368

0015-5691

Academic Journal

10.1254/fpj.24059