The Anabolic Effect of Testosterone on Pelvic Floor Muscles

Study Overview
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Brief Summary
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Stress urinary incontinence is the most common female pelvic floor disorder encountered in clinical practice with significant negative impact on quality of life. The prevalence of urinary incontinence increases with aging, and weakness of the pelvic floor muscles contributes to the development of stress urinary incontinence. Given that androgen receptors are expressed throughout the pelvic floor, the anabolic effects of androgens on pelvic floor muscles may provide a therapeutic option in women with stress urinary incontinence. The investigators are conducting a randomized, double-blind, placebo-controlled proof-of-concept trial in older postmenopausal women with stress urinary incontinence to assess whether testosterone therapy can increase pelvic floor muscles and improve urinary function.

Detailed Description
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The investigators are conducting a 12-week double-blind, randomized-controlled, proof-of-concept pilot trial to determine the anabolic effect of testosterone therapy on pelvic floor muscles in postmenopausal women, 60 years and older, with stress urinary incontinence. The first aim is to compare the efficacy of testosterone supplementation versus placebo on the volume of levator ani muscles of the pelvic floor, assessed by magnetic resonance imaging (MRI). The second aim is to assess the efficacy of testosterone supplementation in improving indices of urodynamic function (i.e., bladder, urethra, and sphincter function), assessed by urodynamic testing. These urodynamic measures include Valsava leak point pressure, urethral pressure profile, cystometry and electromyography. As an exploratory aim, the efficacy of testosterone treatment relative to placebo will be assessed using self-reported urinary symptoms assessed by the Urogenital Distress Inventory (UDI) and quality of life assessed by the Incontinence Impact Questionnaire (IIQ).

Official Title
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A Pilot Study to Evaluate the Anabolic Effect of Testosterone on Muscles of the Pelvic Floor in Older Women With Stress Urinary Incontinence

Conditions
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Stress Urinary Incontinence, Menopause

Intervention / Treatment
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* Drug: Testosterone cypionate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women, age 60 years and older. Medically documented pure stress urinary incontinence on physical exam or urodynamic testing. Normal mammogram within the last 12 months Endometrial thickness of ≤4 mm in women with an intact uterus assessed by endometrial ultrasound. Ability and willingness to provide informed consent. Exclusion Criteria: • Medically documented urge or mixed urinary incontinence (stress and urge) on physical exam or urodynamic testing. Participating in pelvic floor muscle training (PFMT) therapy currently or in the past 3 months Previous pelvic surgery (i.e., hysterectomy, pelvic organ prolapse repair, mid-urethral sling placement, injection of urethral bulking agents) or radiation treatment to the pelvis. History of ≥ Grade 3 pelvic organ prolapse Neurologic disorder causing UI or bladder dysfunction (i.e., multiple sclerosis, Parkinson's disease, stroke, cerebral palsy, spinal cord injury) Current urinary tract infection History of breast or endometrial cancer Use of systemic estrogen therapy in the past 3 months Baseline hematocrit >48%, serum creatinine >2.5 mg/dL; HbA1c >8.0%; BMI >40 kg/m2 Uncontrolled hypertension defined as an average of two blood pressure readings of greater than 160/100. Subjects who are on insulin therapy will be excluded. Uncontrolled congestive heart failure Myocardial infarction, acute coronary syndrome, revascularization surgery or stroke within 6 months History of pulmonary embolism, deep vein thrombosis or a genetic thromboembolic disorder History of bipolar disorder, schizophrenia or untreated major depression Presence of metallic implants (pacemakers, aneurysm clips, etc.) that preclude the patient from undergoing MRI

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Testosterone<br>Testosterone Cypionate 25-mg weekly by intramuscular injection | Drug: Testosterone cypionate<br>* weekly by intramuscular injection<br>|
| Placebo Comparator: Placebo<br>Placebo intramuscular injections weekly | Drug: Placebo<br>* weekly by intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pelvic floor muscle volume | volume of levator ani muscles of the pelvic floor, assessed by magnetic resonance imaging (MRI) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in abdominal leak point pressure | abdominal leak point pressure will be measured by a urodynamic function study | 12 weeks | 
| Change in urine flow rate | urine flow rate will be measured by urodynamic function a study | 12 weeks | 
| Change in bladder pressure | bladder pressure will be measured during filling, storage and voiding by urodynamic study | 12 weeks | 
| Change in post void residual urine volume | post void residual urine volume will be measured using bladder ultrasound | 12 weeks | 
| Change in urinary symptoms | self-reported urinary symptoms will be assessed by the Urogenital Distress Inventory (UDI). Total score ranges from 6-24 with higher scores indicating higher severity of symptoms | 12 weeks | 
| Change in quality of life | quality of life will be assessed by the Incontinence Impact Questionnaire (IIQ). Total score ranges from 0-21 with higher scores indicating worse impact on quality of life. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stress urinary incontinence, testosterone therapy, menopause, pelvic floor disorders