Vaginal Estrogen and Pelvic Floor Physical Therapy in Women With Symptomatic Mild Prolapse

Study Overview
=================
Brief Summary
-----------------
This is a randomized controlled trial in which women with symptomatic mild pelvic organ prolapse undergoing Pelvic Floor Physical Therapy (PFPT) receive vaginal estrogen versus placebo to see if a combined approach to treatment leads to improvement in clinical outcomes. The investigators predict that PFPT in combination with vaginal estrogen will lead to decreased pelvic floor symptoms and improved anatomical support corroborated by biomarker data.

Detailed Description
-----------------
The pathogenesis of pelvic organ prolapse (POP) is unknown. Few studies have correlated patient symptoms and amount of prolapse with biomarkers. POP has traditionally been managed with a pessary or surgery. Recent studies suggest a reduction in POP symptoms following Pelvic Floor Physical Therapy (PFPT). Vaginally delivered hormones are also commonly used to treat prolapse symptoms, with little evidence supporting a clinical benefit. The investigators hypothesize that the optimal approach to improving prolapse symptoms in the patient with mild prolapse requires re-alignment and strengthening of levator muscles via PFPT, and optimization of tissue integrity via local estrogen therapy. The investigators propose to test this hypothesis in a randomized controlled trial in which women with symptomatic mild prolapse opting for PFPT, receive treatment with PFPT in combination with vaginal estrogen versus placebo. The investigators predict that the combined approach will lead to decreased symptoms and improved anatomical support corroborated by biomarker data.

Official Title
-----------------
Impact of Vaginal Estrogen in the Treatment of Symptomatic Mild Pelvic Organ Prolapse With Pelvic Floor Physical Therapy

Conditions
-----------------
Pelvic Organ Prolapse

Intervention / Treatment
-----------------
* Drug: Vaginal estrogen
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women in good health aged 40-80 Has symptoms of pelvic organ prolapse; answers yes to at least 1 of the following questions: Do you feel or see a vaginal bulge? Do you feel pressure in the vagina? Meets POP-Q criteria on exam for stage I, II, or III prolapse Interested in PFPT for management of POP Normal mammogram within 1 year of enrollment Exclusion Criteria: Prior surgery for prolapse or incontinence Other prior interventions for prolapse (e.g. pessary, PFPT) Previous bilateral salpingo-oophorectomy (women with 1 ovary will be eligible) Known liver dysfunction Connective tissue diseases known to affect collagen or elastin remodeling (including: Lupus, Rheumatoid Arthritis, Scleroderma, Sjogrens syndrome, Marfan syndrome, and Ehlers-Danlos syndrome) Unevaluated abnormal vaginal bleeding or abnormal pap smear in the previous year BMI > 35 kg/m2 Estrogen therapy (including birth control) in the previous year Current or prior breast or pelvic malignancy (ovarian, tubal, uterine, cervical or vaginal) Contraindication to hormone use (i.e. thromboembolic disorder, use of anti-coagulants, coronary artery disease, history of stroke)

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaginal estrogen<br>Patients in the experimental group will receive vaginal estrogen cream | Drug: Vaginal estrogen<br>* 1 gram vaginally for 7 days, followed by 1 gram vaginally twice weekly thereafter<br>* Other names: Premarin vaginal cream;|
| Placebo Comparator: Placebo cream<br>Patients in the comparison group will receive placebo vaginal cream | Drug: Placebo<br>* 1 gram vaginally for 7 days, followed by 1 gram vaginally twice weekly thereafter<br>* Other names: Placebo cream;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global impression of improvement in prolapse symptoms, using the PGI-I | To determine the impact of vaginally delivered estrogen on global impression of improvement in women with symptomatic mild pelvic organ prolapse who are undergoing pelvic floor physical therapy | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pelvic floor symptoms, using the PFDI-20 |  | 6 months | 
| Quality of life, using the PFIQ-7 |  | 6 months | 
| Sexual function, using the PISQ-12 |  | 6 months | 
| Pelvic organ prolapse stage, using the POP-Q exam |  | 6 months | 
| Collagenase activity | Vaginal swabs collected from the posterior fornix will be used for biochemical analysis | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Placebo, Pelvic organ prolapse, Pelvic floor physical therapy, Vaginal estrogen