Clinical trial NCT01778985: Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
Official title: Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pelvic Organ Prolapse
Menopause
Keywords: Pelvic organ prolapse
Menopause
Estrogen
Premarin
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: American Urogynecologic Society Foundation Astellas Research Award
First posted: 2013-01-29
Enrollment: 30
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Vaginal Wall Composition: Epithelium (Intention to Treat)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Vaginal Wall Composition: Epithelium (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Vaginal Wall Composition: Muscularis (Intention to Treat)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Vaginal Wall Composition: Muscularis (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: hCOL1A1, Per-Protocol
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Total Collagen Content in Vaginal Muscularis, (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Vaginal Wall Degradative Activity, Muscularis, MMP-9
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Vaginal Wall Composition: Lamina Propria (Intention to Treat)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Vaginal Wall Composition: Lamina Propria (Per-Protocol)
timeFrame: Time of surgery, i.e. 6-8 weeks of intervention
measure: hCOL3, (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Lysyl Oxidase (LOX) (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: LOXL1 (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Tropoelastin (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: TGFB1 (Per-Protocol)
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
measure: Vaginal Wall Degradative Activity, Mucosa, MMP-9
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
Secondary outcomes:
measure: Serum Estrone Levels, Baseline
timeFrame: Baseline
measure: Serum Estrone Levels, Surgery
timeFrame: Time of surgery
measure: Serum Estradiol Levels, Baseline
timeFrame: Baseline
measure: Serum Estradiol Levels, Surgery
timeFrame: Time of surgery
measure: Estimated Blood Loss
timeFrame: Time of surgery, i.e. after 6-8 weeks of intervention
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
References:
citation: Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab. 2014 Oct;99(10):3728-36. doi: 10.1210/jc.2014-1216. Epub 2014 Jun 20.