NIH: National Institutes of Health Bethesda, Maryland, USA.
Curr Opin Endocrinol Diabetes Obes. 2022 Aug 1;29(4):406-412. doi: 10.1097/MED.0000000000000753. Epub 2022 Jul 2.
This review is intended to provide perspective on the history of selective progesterone receptor modulators (SPRMs) and progesterone antagonists, their current availability, therapeutic promise and safety concerns.
Despite keen interest in synthesis of these compounds, only a handful have had clinical test results allowing for commercialization. Mifepristone is well tolerated and effective for single dose first trimester at-home pregnancy termination and is available in much of the world. Ulipristal acetate, at single doses, is well tolerated and effective for emergency contraception, with less availability. Chronic use of these agents has been associated with abnormal liver enzymes, and rarely, with hepatic failure; causality is not understood.
SPRMs and progesterone antagonists have great therapeutic promise for use in other reproductive disorders, including breast cancer, endometriosis, adenomyosis, estrogen-free contraception and cervical ripening but require additional study. Alternative formulations, whether local (topical breast or intrauterine) or extended-release may reduce the incidence of liver function abnormalities and should be explored.
本文旨在从历史角度审视选择性孕激素受体调节剂（SPRMs）和孕激素拮抗剂的发展，讨论它们的临床应用前景、安全性问题和目前的应用现状。
尽管人们热衷于合成这些化合物，但只有少数几种具有商业化的临床测试结果。米非司酮耐受性良好，可有效终止妊娠，并且在世界大部分地区都有应用。左炔诺孕酮单次剂量应用于紧急避孕效果良好，但供应有限。这些药物的长期使用与肝酶异常有关，极少数情况下与肝衰竭有关；但因果关系尚不清楚。
SPRMs 和孕激素拮抗剂在治疗其他生殖系统疾病方面具有广阔的应用前景，包括乳腺癌、子宫内膜异位症、子宫腺肌病、无雌激素避孕和宫颈成熟，但仍需要进一步研究。替代制剂，无论是局部（乳房或子宫内局部）还是缓释制剂，可能会降低肝功能异常的发生率，应加以探索。
