Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
- Registration Number
- NCT01778985
- Lead Sponsor
- University of Texas Southwestern Medical Center
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 30
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Premarin Premarin Premarin cream 0.625mg/1gm. Applied to vagina by applicator as 1gm nightly for 2 weeks then 1gm 2 nights per week for 4-6 weeks or until day of surgery. Placebo Placebo Placebo cream, applied to vagina by applicator as 1gm nightly for 2 weeks then 1gm 2 nights per week for 4-6 weeks or until day of surgery.
- Primary Outcome Measures
Name Time Method hCOL1A1, Per-Protocol Time of surgery, i.e. after 6-8 weeks of intervention Data represent ratio of total mRNA relative to postmenopausal external control.
Vaginal Wall Composition: Epithelium (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Will assess vaginal wall histology - thicknesses of epithelium
Vaginal Wall Composition: Muscularis (Intention to Treat) Time of surgery, i.e. after 6-8 weeks of intervention Will assess vaginal wall histology - thicknesses of muscularis
Total Collagen Content in Vaginal Muscularis, (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Will assess hydroxy-proline assays as index of amount of collagen
Vaginal Wall Composition: Epithelium (Intention to Treat) Time of surgery, i.e. after 6-8 weeks of intervention Will assess vaginal wall histology - thicknesses of epithelium
Vaginal Wall Composition: Muscularis (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Will assess vaginal wall histology - thicknesses of muscularis
Vaginal Wall Composition: Lamina Propria (Per-Protocol) Time of surgery, i.e. 6-8 weeks of intervention Will assess vaginal wall histology - thickness of lamina propria
Lysyl Oxidase (LOX) (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Data represent ratio of total mRNA relative to postmenopausal external control.
Tropoelastin (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Data represent ratio of total mRNA relative to postmenopausal external control.
Vaginal Wall Degradative Activity, Muscularis, MMP-9 Time of surgery, i.e. after 6-8 weeks of intervention Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
Vaginal Wall Composition: Lamina Propria (Intention to Treat) Time of surgery, i.e. after 6-8 weeks of intervention Will assess vaginal wall histology - thickness of lamina propria.
TGFB1 (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Data represent ratio of total mRNA relative to postmenopausal external control.
Vaginal Wall Degradative Activity, Mucosa, MMP-9 Time of surgery, i.e. after 6-8 weeks of intervention Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
hCOL3, (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Data represent ratio of total mRNA relative to postmenopausal external control.
LOXL1 (Per-Protocol) Time of surgery, i.e. after 6-8 weeks of intervention Data represent ratio of total mRNA relative to postmenopausal external control.
- Secondary Outcome Measures
Name Time Method Serum Estradiol Levels, Baseline Baseline Estimated Blood Loss Time of surgery, i.e. after 6-8 weeks of intervention Intraoperative estimated blood loss
Serum Estrone Levels, Baseline Baseline Serum Estrone Levels, Surgery Time of surgery Serum Estradiol Levels, Surgery Time of surgery
Trial Locations
- Locations (1)
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States