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Completed

NCT Number: NCT01778985

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

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.

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Key information

Conditions

Pelvic Organ Prolapse Menopause Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Prolapse

Age range

40 year–70 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Premarin

Drug

Other names: Conjugated equine estrogen

Placebo

Other

Other names: Placebo cream

Primary outcomes

  1. Vaginal Wall Composition: Epithelium (Intention to Treat)

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

    Will assess vaginal wall histology - thicknesses of epithelium

  2. Vaginal Wall Composition: Epithelium (Per-Protocol)

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

    Will assess vaginal wall histology - thicknesses of epithelium

  3. Vaginal Wall Composition: Muscularis (Intention to Treat)

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

    Will assess vaginal wall histology - thicknesses of muscularis

  4. Vaginal Wall Composition: Muscularis (Per-Protocol)

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

    Will assess vaginal wall histology - thicknesses of muscularis

  5. hCOL1A1, Per-Protocol

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

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

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

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

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

  7. Vaginal Wall Degradative Activity, Muscularis, MMP-9

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

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

  8. Vaginal Wall Composition: Lamina Propria (Intention to Treat)

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

    Will assess vaginal wall histology - thickness of lamina propria.

  9. Vaginal Wall Composition: Lamina Propria (Per-Protocol)

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

    Will assess vaginal wall histology - thickness of lamina propria

  10. hCOL3, (Per-Protocol)

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

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

  11. Lysyl Oxidase (LOX) (Per-Protocol)

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

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

  12. LOXL1 (Per-Protocol)

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

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

  13. Tropoelastin (Per-Protocol)

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

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

  14. TGFB1 (Per-Protocol)

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

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

  15. Vaginal Wall Degradative Activity, Mucosa, MMP-9

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

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

Secondary outcomes

  1. Serum Estrone Levels, Baseline

    Time frame: Baseline

  2. Serum Estrone Levels, Surgery

    Time frame: Time of surgery

  3. Serum Estradiol Levels, Baseline

    Time frame: Baseline

  4. Serum Estradiol Levels, Surgery

    Time frame: Time of surgery

  5. Estimated Blood Loss

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

    Intraoperative estimated blood loss

Sponsors and collaborators

Lead sponsor

University of Texas Southwestern Medical Center

Other

Collaborators

  • American Urogynecologic Society Foundation Astellas Research Award

Registry information

Acronym: PET

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Jan 29, 2013
Registry last updated
Oct 2, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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