Clinical trial NCT06111209: The Anabolic Effect of Testosterone on Pelvic Floor Muscles
Official title: A Pilot Study to Evaluate the Anabolic Effect of Testosterone on Muscles of the Pelvic Floor in Older Women With Stress Urinary Incontinence
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Stress Urinary Incontinence
Menopause
Keywords: stress urinary incontinence
testosterone therapy
menopause
pelvic floor disorders
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-11-01
Enrollment: 30
Sex: FEMALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in pelvic floor muscle volume
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in abdominal leak point pressure
timeFrame: 12 weeks
measure: Change in urine flow rate
timeFrame: 12 weeks
measure: Change in bladder pressure
timeFrame: 12 weeks
measure: Change in post void residual urine volume
timeFrame: 12 weeks
measure: Change in urinary symptoms
timeFrame: 12 weeks
measure: Change in quality of life
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Grace Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: