Abstract
Background
Vaginal atrophy (VA) is a prevalent disorder in postmenopausal women that is characterized
by decreased epithelial thickness, reduced vaginal maturation index (VMI) and increased
vaginal pH. Current medical therapy consists of local or systemic replacement of estrogens.
Objective
The goal of this study was to understand, at a molecular level, the effect of estradiol
(E2) on the vaginal epithelium.
Methods
Nineteen women were treated with E2 delivered through a skin patch at a dose of 0.05 mg/day for 12 weeks. The diagnosis of VA was confirmed by a VMI with ≤5% superficial
cells and vaginal pH > 5.0. Vaginal biopsy samples were collected at baseline and after treatment. Differentially
expressed mRNA transcripts in these biopsies were determined by microarray analysis.
Results
All 19 subjects had increased VMI (>5%) and/or reduced pH (≤5) following treatment.
Most subjects also had increased serum E2 levels and reduced serum FSH levels. Transcriptional
profiling of vaginal biopsies identified over 3000 E2-regulated genes, including those
involved in several key pathways known to regulate cell growth and proliferation,
barrier function and pathogen defense.
Conclusions
E2 controls a plethora of cellular pathways that are concordant with its profound
effect on vaginal physiology. The data presented here are a useful step toward understanding
the role of E2 in vaginal tissue and the development of novel therapeutics for the
treatment of VA.
Abbreviations:
VA (vaginal atrophy), VMI (vaginal maturation index), E2 (17β-estradiol), FSH (follicle stimulating hormone), FDR (false discovery rate)Keywords
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Article info
Publication history
Published online: October 16, 2007
Accepted:
September 17,
2007
Received in revised form:
September 11,
2007
Received:
May 23,
2007
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
