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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pelvic Organ Prolapse
• Intervention / Treatment: Drug: Vaginal estrogen; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital, University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Improvement	The Patient Global Impression of Improvement (PGI-I) is a global index that may be used to rate the response of a condition to a therapy (transition scale). It is a simple, direct, easy to use scale that is intuitively understandable to clinicians. Potential Responses: Very Much Better; Much Better; A Little Better; No Change 5, A Little Worse 6. Much Worse 7. Very Much Worse Lower scores indicate more imiprovment / better outcome.	6 months after starting vaginal cream

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pelvic Floor Symptoms	Pelvic Floor Symptoms, using the PFDI-20. The Pelvic Floor Distress Inventory is a condition specific quality of life instrument that assesses distress from pelvic organ prolapse, colorectal-anal, and urinary symptoms. Higher scores indicate greater disease burden. Range: 0 to 300	6 months
General Quality of Life	Quality of Life, using the PFIQ-7 The Pelvic Floor Impact Questionnaire assesses how bladder, bowel, and vaginal symptoms affect activity, relationships, ad feelings. Higher numbers indicate greater disease burden. Score range: 0 to 300	6 months
Pelvic Organ Prolapse Stage	Pelvic Organ Prolapse Stage, using the POP-Q exam. The Pelvic Organ Prolapse Quantification System use 9 measurements in the vagina to assess prolapse stage. Higher stage indicates greater prolapse. Range: 0 to 4	6 months
Collagenase Activity	Collagenase Activity, via vaginal swabs collected from the posterior fornix will be used for biochemical analysis.	6 months
Sexual Function	Sexual Function, using the PISQ-12 The Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire evaluates sexual function in patients with incontinence and/or vaginal prolapse. Higher scores indicate greater disease burden. Scale: 0 to 48	6 months

Collaborators and Investigators

• Sponsor: Pamela Moalli
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Pfizer; National Institutes of Health (NIH); American Urogynecologic Society
• Investigators: Study Director: Laura C Skoczylas, MD, MS, University of Pittsburgh; Principal Investigator: Pamela Moalli, MD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 2, 2023
• Study Completion (Actual): March 2, 2023

Study Registration Dates

• First Submitted: July 19, 2012
• First Submitted That Met QC Criteria: July 23, 2012
• First Posted (Estimated): July 24, 2012

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 13, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Placebo; Pelvic organ prolapse; Pelvic floor physical therapy; Vaginal estrogen
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Prolapse; Pelvic Organ Prolapse; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens
• Other Study ID Numbers: STUDY19030408; R01HD061811 (U.S. NIH Grant/Contract)