A study of 17β-estradiol-regulated genes in the vagina of postmenopausal women with vaginal atrophy

MM Cotreau, VM Chennathukuzhi, HA Harris, L Han… - Maturitas, 2007 - Elsevier
MM Cotreau, VM Chennathukuzhi, HA Harris, L Han, AJ Dorner, G Apseloff, U Varadarajan…
Maturitas, 2007Elsevier
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 …
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 0.05mg/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.
Elsevier