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

University of Texas Southwestern Medical Center30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Pelvic Organ Prolapse Menopause

Interventions

Eligibility

Sex: FEMALEMin age: 40 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Vaginal Wall Composition: Epithelium (Intention to Treat)

Will assess vaginal wall histology - thicknesses of epithelium

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Vaginal Wall Composition: Epithelium (Per-Protocol)

Will assess vaginal wall histology - thicknesses of epithelium

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Vaginal Wall Composition: Muscularis (Intention to Treat)

Will assess vaginal wall histology - thicknesses of muscularis

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Vaginal Wall Composition: Muscularis (Per-Protocol)

Will assess vaginal wall histology - thicknesses of muscularis

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

hCOL1A1, Per-Protocol

Data represent ratio of total mRNA relative to postmenopausal external control.

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Total Collagen Content in Vaginal Muscularis, (Per-Protocol)

Will assess hydroxy-proline assays as index of amount of collagen

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Vaginal Wall Degradative Activity, Muscularis, MMP-9

Will assess zymograms for total matrix metalloprotease (MMP) 9 activity

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Vaginal Wall Composition: Lamina Propria (Intention to Treat)

Will assess vaginal wall histology - thickness of lamina propria.

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Vaginal Wall Composition: Lamina Propria (Per-Protocol)

Will assess vaginal wall histology - thickness of lamina propria

Time frame: Time of surgery, i.e. 6-8 weeks of intervention

hCOL3, (Per-Protocol)

Data represent ratio of total mRNA relative to postmenopausal external control.

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Lysyl Oxidase (LOX) (Per-Protocol)

Data represent ratio of total mRNA relative to postmenopausal external control.

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

LOXL1 (Per-Protocol)

Data represent ratio of total mRNA relative to postmenopausal external control.

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Tropoelastin (Per-Protocol)

Data represent ratio of total mRNA relative to postmenopausal external control.

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

TGFB1 (Per-Protocol)

Data represent ratio of total mRNA relative to postmenopausal external control.

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Vaginal Wall Degradative Activity, Mucosa, MMP-9

Will assess zymograms for total matrix metalloprotease (MMP) 9 activity

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

Secondary Outcomes

Serum Estrone Levels, Baseline

Time frame: Baseline

Serum Estrone Levels, Surgery

Time frame: Time of surgery

Serum Estradiol Levels, Baseline

Time frame: Baseline

Serum Estradiol Levels, Surgery

Time frame: Time of surgery

Estimated Blood Loss

Intraoperative estimated blood loss

Time frame: Time of surgery, i.e. after 6-8 weeks of intervention

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes