配体-孕激素受体通路调节的子宫内膜反应是可逆的。

The endometrial response to modulation of ligand-progesterone receptor pathways is reversible.

机构信息

Medical Research Council Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, United Kingdom.

出版信息

Fertil Steril. 2021 Sep;116(3):882-895. doi: 10.1016/j.fertnstert.2021.02.008. Epub 2021 Apr 14.

DOI:10.1016/j.fertnstert.2021.02.008

PMID:33865567

Abstract

OBJECTIVE

To study the impact of the progesterone receptor modulator (PRM), ulipristal acetate (UPA), on endometrial morphology and function.

DESIGN

Cross-sectional.

SETTING

University Research Institute.

PATIENT(S): Endometrial biopsies from 16 patients with heavy menstrual bleeding with a structurally normal uterus or in association with structural abnormalities identified on radiological imaging (fibroids, adenomyosis or a combination of fibroids and adenomyosis).

INTERVENTION(S): Participants received UPA (5 mg once daily) for three 12-week courses, each separated by 4 weeks without treatment.

MAIN OUTCOME MEASURE(S): Gene expression by real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and digital image analysis were analyzed to investigate the endometrial impact of modulation of progesterone receptor pathways upon expression of steroid receptors, steroid metabolizing enzymes, cell proliferation, and progesterone-regulated genes in the same patients at 3 time points: before, during, and after discontinuation of PRM treatment.

RESULT(S): Ulipristal acetate treatment resulted in increased messenger ribonucleic acid (mRNA) levels of steroid receptors compared with pretreatment secretory endometrium; decreased mRNA levels of 17- and 11-beta-hydroxysteroid dehydrogenases compared with pretreatment proliferative endometrium and pretreatment secretory endometrium; reduced cell proliferation compared with pretreatment proliferative endometrium; and altered mRNA levels of progesterone-regulated genes. A strong consistency between immunohistochemistry-digital image analysis and real-time quantitative reverse transcription polymerase chain reaction results was evident. Alterations in the mRNA levels and endometrial morphology returned to a pretreatment phenotype after the cessation of PRM exposure.

CONCLUSION(S): The endometrial impact of the modulation of progesterone receptor pathways with PRM (UPA) treatment is reversible.

CLINICAL TRIAL REGISTRATION NUMBER

Ulipristal acetate versus conventional management of heavy menstrual bleeding (UCON) trial (EudraCT 2014-003408-65; REC14/LO/1602).

摘要

目的

研究孕激素受体调节剂（PRM）醋酸乌利司他（UPA）对子宫内膜形态和功能的影响。

设计

横断面研究。

地点

大学研究所。

患者

16 例因月经过多而就诊的患者，这些患者的子宫结构正常或在影像学检查（肌瘤、腺肌病或肌瘤和腺肌病的组合）中发现结构异常。

干预措施

参与者接受 UPA（每天一次 5mg）治疗，共三个 12 周疗程，每个疗程之间间隔 4 周无治疗。

主要观察指标

通过实时定量逆转录聚合酶链反应、免疫组织化学和数字图像分析来研究孕激素受体途径调节对甾体受体、甾体代谢酶、细胞增殖和孕激素调节基因表达的影响，同一患者在 3 个时间点（治疗前、治疗期间和治疗结束后）的子宫内膜影响。

结果

与治疗前分泌期子宫内膜相比，醋酸乌利司他治疗导致甾体受体的信使核糖核酸（mRNA）水平升高；与治疗前增殖期子宫内膜和治疗前分泌期子宫内膜相比，17-和 11-β-羟甾脱氢酶的 mRNA 水平降低；与治疗前增殖期子宫内膜相比，细胞增殖减少；孕激素调节基因的 mRNA 水平发生改变。免疫组织化学-数字图像分析和实时定量逆转录聚合酶链反应结果之间具有很强的一致性。停止 PRM 暴露后，mRNA 水平和子宫内膜形态恢复到治疗前的表型。