Phase 4 N=30 Randomized Quadruple-blind Basic Science

Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor

Pelvic Organ Prolapse · Menopause

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View on ClinicalTrials.gov: NCT01778985 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Sep 2014

Primary outcome: Primary: Vaginal Wall Composition: Epithelium (Intention to Treat) — 413.9; 314.1 microns — p=0.21

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Premarin (Drug); Placebo (Other)
Age: Adult, Older Adult · 40+ yrs
Sex: Female
Sponsor: University of Texas Southwestern Medical Center
Primary completion: Mar 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Vaginal Wall Composition: Epithelium (Intention to Treat)	413.9; 314.1	0.21
PRIMARY Vaginal Wall Composition: Epithelium (Per-Protocol)	550.5; 314.1	0.002 sig
PRIMARY Vaginal Wall Composition: Muscularis (Intention to Treat)	5670.4; 2807.1	0.22
PRIMARY Vaginal Wall Composition: Muscularis (Per-Protocol)	7570.7; 2807.1	0.088
PRIMARY hCOL1A1, Per-Protocol	2.19; 0.37	<0.001 sig
PRIMARY Total Collagen Content in Vaginal Muscularis, (Per-Protocol)	302.6; 94.86	0.10
PRIMARY Vaginal Wall Degradative Activity, Muscularis, MMP-9	37.03; 132.34	0.020 sig
PRIMARY Vaginal Wall Composition: Lamina Propria (Intention to Treat)	1042.3; 895.1	0.53
PRIMARY Vaginal Wall Composition: Lamina Propria (Per-Protocol)	1133.4; 895.1	0.33
PRIMARY hCOL3, (Per-Protocol)	.92; .37	0.05
PRIMARY Lysyl Oxidase (LOX) (Per-Protocol)	.74; .51	0.15
PRIMARY LOXL1 (Per-Protocol)	.64; .69	0.82
PRIMARY Tropoelastin (Per-Protocol)	.78; .69	0.70
PRIMARY TGFB1 (Per-Protocol)	.61; .81	0.25
PRIMARY Vaginal Wall Degradative Activity, Mucosa, MMP-9	8.97; 56.73	0.06
SECONDARY Serum Estrone Levels, Baseline	18.0; 18.5	0.91
SECONDARY Serum Estrone Levels, Surgery	22.8; 24.9	0.78
SECONDARY Serum Estradiol Levels, Baseline	11.1; 8.4	0.51
SECONDARY Serum Estradiol Levels, Surgery	7.8; 11.6	0.24
SECONDARY Estimated Blood Loss	285; 285	1

Summary

This is a study to determine how vaginal estrogen cream given for several weeks before pelvic reconstructive therapy will effect elastic fiber assembly in the muscularis layer of the vaginal wall. Postmenopausal women with at least Stage 2 pelvic organ prolapse will receive either estrogen vaginal cream or placebo cream 6-8 weeks prior to reconstructive surgery. At time of surgery, full thickness biopsies will be obtained from a standardized location at the top of vagina. The investigators will measure the thickness of the vaginal muscularis, elastic fiber number and morphology, and analyze if elastic fiber synthesis or degradation is affected by estrogen therapy. The results will provide important data to support a larger clinical trial to determine if preoperative and maintenance estrogen therapy alter long-term success rates of pelvic reconstructive surgery for pelvic organ prolapse.

Eligibility Criteria

Inclusion Criteria

Women, still with uterus, planning total hysterectomy as part of surgical repair for pelvic organ prolapse
Symptomatic anterior and/or apical vaginal prolapse greater than or equal to Stage 2 (i.e., bulge extends to at least 1 cm of the hymen or beyond)
Women between 1 and 10 years after menopause. Menopause is defined as one year of amenorrhea or surgical ovariectomy.
Age 40-70 years old
No estrogen replacement therapy in the last 1 month
Physically capable of daily application of vaginal cream

Exclusion Criteria

BMI >35
Prior surgical repair of prolapse involving the vaginal cuff.
Prior total hysterectomy
Premenopausal or postmenopausal >10 years
Prior steroid hormone replacement therapy of duration >1 month (oral or vaginal estrogen, testosterone or corticosteroids)
History of connective tissue disease (Ehlers-Danlos, Marfan, etc)
History of vaginal radiation
Contraindications for estrogen replacement therapy (current, or history of, spontaneous deep vein thrombosis, stroke, coronary artery disease, breast or endometrial cancer)
Concurrent use of steroid cream for treatment of Lichen sclerosis
Recent history (within last month) of vaginal infection or vaginitis
Current tobacco use

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Data sourced from ClinicalTrials.gov (NCT01778985). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.