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

NCT01778985 | Completed Phase 4 Results

• 1 other identifier: STU-042011-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Pelvic Organ Prolapse; Menopause

Keywords

Pelvic organ prolapse; Menopause; Estrogen; Premarin

Outcome Measures

Primary Outcomes (15)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (5)

• Serum Estrone Levels, Baseline

  Baseline

• Serum Estrone Levels, Surgery

  Time of surgery

• Serum Estradiol Levels, Baseline

  Baseline

• Serum Estradiol Levels, Surgery

  Time of surgery

• Estimated Blood Loss

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

Study Arms (2)

Premarin

EXPERIMENTAL

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.

Drug: Premarin

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Premarin DRUG

Also known as: Conjugated equine estrogen

Premarin

Placebo OTHER

Also known as: Placebo cream

Placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• American Urogynecologic Society Foundation Astellas Research Award: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• 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.

  PMID: 24947034 DERIVED

MeSH Terms

Conditions

Pelvic Organ Prolapse

Interventions

Estrogens, Conjugated (USP)

Condition Hierarchy (Ancestors)

Prolapse; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

4 patients nonadherent to study protocol in the Premarin arm.

Results Point of Contact

• Title: David D. Rahn, M.D.
• Organization: University of Texas Southwestern Medical Center

david.rahn@utsouthwestern.edu

214-648-6430

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Dept. of Obstetrics & Gynecology

Study Record Dates

• First Submitted: January 23, 2013
• First Posted: January 29, 2013
• Study Start: December 1, 2012
• Primary Completion: March 1, 2013
• Study Completion: April 1, 2013
• Last Updated: October 2, 2014
• Results First Posted: September 10, 2014

Record last verified: 2014-09

Locations

US (1)