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Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert

OBJECTIVE: To evaluate endometrial progesterone receptor (PGR) expression in menopausal women who used vaginal 4-μg and 10-μg estradiol (E2) inserts or placebo. METHODS: REJOICE was a randomized, placebo-controlled trial investigating vaginal E2 inserts in women with moderate to severe dyspareunia d...

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Autores principales: Mirkin, Sebastian, Simon, James A., Liu, James H., Archer, David F., Castro, Patricia D., Graham, Shelli, Bernick, Brian, Komm, Barry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386586/
https://www.ncbi.nlm.nih.gov/pubmed/34054104
http://dx.doi.org/10.1097/GME.0000000000001801
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author Mirkin, Sebastian
Simon, James A.
Liu, James H.
Archer, David F.
Castro, Patricia D.
Graham, Shelli
Bernick, Brian
Komm, Barry
author_facet Mirkin, Sebastian
Simon, James A.
Liu, James H.
Archer, David F.
Castro, Patricia D.
Graham, Shelli
Bernick, Brian
Komm, Barry
author_sort Mirkin, Sebastian
collection PubMed
description OBJECTIVE: To evaluate endometrial progesterone receptor (PGR) expression in menopausal women who used vaginal 4-μg and 10-μg estradiol (E2) inserts or placebo. METHODS: REJOICE was a randomized, placebo-controlled trial investigating vaginal E2 inserts in women with moderate to severe dyspareunia due to menopause. In this post hoc analysis, 25 eligible women with endometrial biopsies were randomly selected from each treatment group (4-μg and 10-μg E2 vaginal inserts and placebo). Endometrial biopsy sections were immunostained using an anti-PR (A and B) monoclonal antibody. Cell staining was quantified using an artificial intelligence feature-recognition algorithm. Mean PGR expression levels were analyzed between baseline and week 12. RESULTS: PGR expression results were available for 22 women in the 4-μg E2 group, and 25 women each for the 10-μg E2 and placebo groups. Similar PGR expression levels were observed at baseline (0.301-0.470 pmol/mg) and after 12 weeks of treatment (0.312-0.432 pmol/mg) for all treatment groups, with no significant differences between baseline and week 12. CONCLUSIONS: No meaningful differences in endometrial PGR expression were observed with the vaginal E2 (4- and 10-μg) inserts at week 12 from baseline, supporting the hypothesis that local exposure to E2 from a low-dose, vaginal insert placed near the vaginal introitus will not be sufficient to upregulate endometrial PGR expression. Coupled with the lack of histologic changes and systemic absorption, our data suggest that these softgel vaginal E2 inserts would not be expected to stimulate endometrial hyperplasia leading to a potential endometrial safety issue in postmenopausal women with moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy. Further study on the endometrial safety of softgel vaginal E2 inserts is under way.
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spelling pubmed-83865862021-09-01 Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert Mirkin, Sebastian Simon, James A. Liu, James H. Archer, David F. Castro, Patricia D. Graham, Shelli Bernick, Brian Komm, Barry Menopause Original Studies OBJECTIVE: To evaluate endometrial progesterone receptor (PGR) expression in menopausal women who used vaginal 4-μg and 10-μg estradiol (E2) inserts or placebo. METHODS: REJOICE was a randomized, placebo-controlled trial investigating vaginal E2 inserts in women with moderate to severe dyspareunia due to menopause. In this post hoc analysis, 25 eligible women with endometrial biopsies were randomly selected from each treatment group (4-μg and 10-μg E2 vaginal inserts and placebo). Endometrial biopsy sections were immunostained using an anti-PR (A and B) monoclonal antibody. Cell staining was quantified using an artificial intelligence feature-recognition algorithm. Mean PGR expression levels were analyzed between baseline and week 12. RESULTS: PGR expression results were available for 22 women in the 4-μg E2 group, and 25 women each for the 10-μg E2 and placebo groups. Similar PGR expression levels were observed at baseline (0.301-0.470 pmol/mg) and after 12 weeks of treatment (0.312-0.432 pmol/mg) for all treatment groups, with no significant differences between baseline and week 12. CONCLUSIONS: No meaningful differences in endometrial PGR expression were observed with the vaginal E2 (4- and 10-μg) inserts at week 12 from baseline, supporting the hypothesis that local exposure to E2 from a low-dose, vaginal insert placed near the vaginal introitus will not be sufficient to upregulate endometrial PGR expression. Coupled with the lack of histologic changes and systemic absorption, our data suggest that these softgel vaginal E2 inserts would not be expected to stimulate endometrial hyperplasia leading to a potential endometrial safety issue in postmenopausal women with moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy. Further study on the endometrial safety of softgel vaginal E2 inserts is under way. Lippincott Williams & Wilkins 2021-05-28 /pmc/articles/PMC8386586/ /pubmed/34054104 http://dx.doi.org/10.1097/GME.0000000000001801 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Studies
Mirkin, Sebastian
Simon, James A.
Liu, James H.
Archer, David F.
Castro, Patricia D.
Graham, Shelli
Bernick, Brian
Komm, Barry
Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert
title Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert
title_full Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert
title_fullStr Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert
title_full_unstemmed Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert
title_short Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert
title_sort evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert
topic Original Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386586/
https://www.ncbi.nlm.nih.gov/pubmed/34054104
http://dx.doi.org/10.1097/GME.0000000000001801
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