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

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Authors:

Rohan R. Chodankar, M.D., Alison Murray, Ph.D., Moira Nicol, Ph.D., Lucy H.R. Whitaker, M.D., Alistair R.W. Williams, M.D., Hilary O.D. Critchley, M.D. 

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)

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.