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

Menopause Clinical Trial

— PET  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01778985
• Other study ID #: STU-042011-101
• Status: Completed
• Phase: Phase 4
• First received: January 23, 2013
• Last updated: September 18, 2014
• Start date: December 2012
• Est. completion date: April 2013

Study information

• Verified date: September 2014
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Menopause
• Pelvic Organ Prolapse
• Prolapse

Intervention

Drug:
• Premarin

Other:
• Placebo

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	American Urogynecologic Society Foundation Astellas Research Award

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vaginal Wall Composition: Epithelium (Intention to Treat)	Will assess vaginal wall histology - thicknesses of epithelium	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Vaginal Wall Composition: Epithelium (Per-Protocol)	Will assess vaginal wall histology - thicknesses of epithelium	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Vaginal Wall Composition: Muscularis (Intention to Treat)	Will assess vaginal wall histology - thicknesses of muscularis	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Vaginal Wall Composition: Muscularis (Per-Protocol)	Will assess vaginal wall histology - thicknesses of muscularis	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	hCOL1A1, Per-Protocol	Data represent ratio of total mRNA relative to postmenopausal external control.	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Total Collagen Content in Vaginal Muscularis, (Per-Protocol)	Will assess hydroxy-proline assays as index of amount of collagen	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Vaginal Wall Degradative Activity, Muscularis, MMP-9	Will assess zymograms for total matrix metalloprotease (MMP) 9 activity	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Vaginal Wall Composition: Lamina Propria (Intention to Treat)	Will assess vaginal wall histology - thickness of lamina propria.	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Vaginal Wall Composition: Lamina Propria (Per-Protocol)	Will assess vaginal wall histology - thickness of lamina propria	Time of surgery, i.e. 6-8 weeks of intervention	No
Primary	hCOL3, (Per-Protocol)	Data represent ratio of total mRNA relative to postmenopausal external control.	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Lysyl Oxidase (LOX) (Per-Protocol)	Data represent ratio of total mRNA relative to postmenopausal external control.	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	LOXL1 (Per-Protocol)	Data represent ratio of total mRNA relative to postmenopausal external control.	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Tropoelastin (Per-Protocol)	Data represent ratio of total mRNA relative to postmenopausal external control.	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	TGFB1 (Per-Protocol)	Data represent ratio of total mRNA relative to postmenopausal external control.	Time of surgery, i.e. after 6-8 weeks of intervention	No
Primary	Vaginal Wall Degradative Activity, Mucosa, MMP-9	Will assess zymograms for total matrix metalloprotease (MMP) 9 activity	Time of surgery, i.e. after 6-8 weeks of intervention	No
Secondary	Serum Estrone Levels, Baseline		Baseline	No
Secondary	Serum Estrone Levels, Surgery		Time of surgery	No
Secondary	Serum Estradiol Levels, Baseline		Baseline	No
Secondary	Serum Estradiol Levels, Surgery		Time of surgery	No
Secondary	Estimated Blood Loss	Intraoperative estimated blood loss	Time of surgery, i.e. after 6-8 weeks of intervention	No