Effect of Preoperative Estrogen Treatment on Connective Tissues of the Pelvic Floor
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- hCOL1A1, Per-Protocol
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Premarin
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.
干预措施: Premarin (Drug)
Placebo
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.
干预措施: Placebo (Other)
结局指标
主要结局
hCOL1A1, Per-Protocol
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Data represent ratio of total mRNA relative to postmenopausal external control.
Vaginal Wall Composition: Epithelium (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess vaginal wall histology - thicknesses of epithelium
Vaginal Wall Composition: Muscularis (Intention to Treat)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess vaginal wall histology - thicknesses of muscularis
Total Collagen Content in Vaginal Muscularis, (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess hydroxy-proline assays as index of amount of collagen
Vaginal Wall Composition: Epithelium (Intention to Treat)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess vaginal wall histology - thicknesses of epithelium
Vaginal Wall Composition: Muscularis (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess vaginal wall histology - thicknesses of muscularis
Vaginal Wall Composition: Lamina Propria (Per-Protocol)
时间窗: Time of surgery, i.e. 6-8 weeks of intervention
Will assess vaginal wall histology - thickness of lamina propria
Lysyl Oxidase (LOX) (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Data represent ratio of total mRNA relative to postmenopausal external control.
Tropoelastin (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Data represent ratio of total mRNA relative to postmenopausal external control.
Vaginal Wall Degradative Activity, Muscularis, MMP-9
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
Vaginal Wall Composition: Lamina Propria (Intention to Treat)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess vaginal wall histology - thickness of lamina propria.
TGFB1 (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Data represent ratio of total mRNA relative to postmenopausal external control.
Vaginal Wall Degradative Activity, Mucosa, MMP-9
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Will assess zymograms for total matrix metalloprotease (MMP) 9 activity
hCOL3, (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Data represent ratio of total mRNA relative to postmenopausal external control.
LOXL1 (Per-Protocol)
时间窗: Time of surgery, i.e. after 6-8 weeks of intervention
Data represent ratio of total mRNA relative to postmenopausal external control.
次要结局
- Serum Estradiol Levels, Baseline(Baseline)
- Estimated Blood Loss(Time of surgery, i.e. after 6-8 weeks of intervention)
- Serum Estrone Levels, Baseline(Baseline)
- Serum Estrone Levels, Surgery(Time of surgery)
- Serum Estradiol Levels, Surgery(Time of surgery)
研究者
David Rahn, MD
Assistant Professor, Dept. of Obstetrics & Gynecology
University of Texas Southwestern Medical Center