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Systemic estradiol levels with low-dose vaginal estrogens

OBJECTIVES: To critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women. METHODS: Pu...

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Autores principales: Santen, Richard J., Mirkin, Sebastian, Bernick, Brian, Constantine, Ginger D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott-Raven Publishers 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050796/
https://www.ncbi.nlm.nih.gov/pubmed/31794498
http://dx.doi.org/10.1097/GME.0000000000001463
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author Santen, Richard J.
Mirkin, Sebastian
Bernick, Brian
Constantine, Ginger D.
author_facet Santen, Richard J.
Mirkin, Sebastian
Bernick, Brian
Constantine, Ginger D.
author_sort Santen, Richard J.
collection PubMed
description OBJECTIVES: To critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women. METHODS: PubMed was searched for studies reporting systemic estradiol levels with lower-dose vaginal estrogens (≤25 μg estradiol or 0.3 mg conjugated equine estrogens). Estradiol levels at baseline and during treatment, area under the curve, and maximum estradiol concentrations were summarized by dose within assay type. A proposed range of systemic estradiol in normal, untreated, postmenopausal women was estimated by conservatively pooling means and standard deviations from published studies. RESULTS: Mean basal estradiol levels were 3.1 to 4.9 pg/mL using liquid or gas chromatography/mass spectroscopy (LC or GC/MS/MS) with a range of undetectable to 10.5 pg/mL using radioimmunoassay. Systemic estradiol levels with vaginal estrogens reflected their doses as measured with LC or GC/MS/MS in different studies: 7.1 to 9.1 pg/mL and 16.7 to 22.7 pg/mL with a 25-μg softgel capsule insert and a tablet insert, respectively; 4.6 to 7.4 pg/mL and 6.6 to 14.8 pg/mL with a 10-μg softgel capsule and a tablet insert, respectively; and 3.6 to 3.9 pg/mL with a 4-μg softgel capsule insert. A mean systemic estradiol concentration ranging from undetectable to 10.7 pg/mL is proposed as an estimate for basal estradiol levels in normal, untreated, postmenopausal women. Systemic estradiol absorption may be influenced by the placement of estradiol higher (as with an applicator) versus lower (as without an applicator) in the vagina, as estradiol transport to the uterus would be more likely further away than closer to the introitus. CONCLUSION: Serum estradiol concentrations were generally lower when measured with more specific and sensitive assays. Estradiol absorption was dose-dependent, and may be influenced by dose, formulation, and positioning in the vagina. Very low systemic estradiol absorption with low/ultralow-dose vaginal estrogens may potentially decrease any adverse events that may be associated with higher doses of vaginal estrogens used for treating moderate to severe VVA due to less estradiol exposure.
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spelling pubmed-70507962020-03-19 Systemic estradiol levels with low-dose vaginal estrogens Santen, Richard J. Mirkin, Sebastian Bernick, Brian Constantine, Ginger D. Menopause Review Articles OBJECTIVES: To critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women. METHODS: PubMed was searched for studies reporting systemic estradiol levels with lower-dose vaginal estrogens (≤25 μg estradiol or 0.3 mg conjugated equine estrogens). Estradiol levels at baseline and during treatment, area under the curve, and maximum estradiol concentrations were summarized by dose within assay type. A proposed range of systemic estradiol in normal, untreated, postmenopausal women was estimated by conservatively pooling means and standard deviations from published studies. RESULTS: Mean basal estradiol levels were 3.1 to 4.9 pg/mL using liquid or gas chromatography/mass spectroscopy (LC or GC/MS/MS) with a range of undetectable to 10.5 pg/mL using radioimmunoassay. Systemic estradiol levels with vaginal estrogens reflected their doses as measured with LC or GC/MS/MS in different studies: 7.1 to 9.1 pg/mL and 16.7 to 22.7 pg/mL with a 25-μg softgel capsule insert and a tablet insert, respectively; 4.6 to 7.4 pg/mL and 6.6 to 14.8 pg/mL with a 10-μg softgel capsule and a tablet insert, respectively; and 3.6 to 3.9 pg/mL with a 4-μg softgel capsule insert. A mean systemic estradiol concentration ranging from undetectable to 10.7 pg/mL is proposed as an estimate for basal estradiol levels in normal, untreated, postmenopausal women. Systemic estradiol absorption may be influenced by the placement of estradiol higher (as with an applicator) versus lower (as without an applicator) in the vagina, as estradiol transport to the uterus would be more likely further away than closer to the introitus. CONCLUSION: Serum estradiol concentrations were generally lower when measured with more specific and sensitive assays. Estradiol absorption was dose-dependent, and may be influenced by dose, formulation, and positioning in the vagina. Very low systemic estradiol absorption with low/ultralow-dose vaginal estrogens may potentially decrease any adverse events that may be associated with higher doses of vaginal estrogens used for treating moderate to severe VVA due to less estradiol exposure. Lippincott-Raven Publishers 2019-12-02 /pmc/articles/PMC7050796/ /pubmed/31794498 http://dx.doi.org/10.1097/GME.0000000000001463 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society. http://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
spellingShingle Review Articles
Santen, Richard J.
Mirkin, Sebastian
Bernick, Brian
Constantine, Ginger D.
Systemic estradiol levels with low-dose vaginal estrogens
title Systemic estradiol levels with low-dose vaginal estrogens
title_full Systemic estradiol levels with low-dose vaginal estrogens
title_fullStr Systemic estradiol levels with low-dose vaginal estrogens
title_full_unstemmed Systemic estradiol levels with low-dose vaginal estrogens
title_short Systemic estradiol levels with low-dose vaginal estrogens
title_sort systemic estradiol levels with low-dose vaginal estrogens
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050796/
https://www.ncbi.nlm.nih.gov/pubmed/31794498
http://dx.doi.org/10.1097/GME.0000000000001463
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