The Anabolic Effect of Testosterone on Pelvic Floor Muscles

Menopause Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06111209
• Other study ID #: 2023P002632
• Secondary ID: R01DK136904
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2024
• Est. completion date: July 2026

Study information

• Verified date: October 2023
• Source: Brigham and Women's Hospital
• Contact: Grace Huang, MD
• Phone: 6175259192
• Email: ghuang7[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Enuresis
• Menopause
• Stress Urinary Incontinence
• Urinary Incontinence
• Urinary Incontinence, Stress

Intervention

Drug:
• Testosterone cypionate
weekly by intramuscular injection
• Placebo
weekly by intramuscular injection

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pelvic floor muscle volume	volume of levator ani muscles of the pelvic floor, assessed by magnetic resonance imaging (MRI)	12 weeks
Secondary	Change in abdominal leak point pressure	abdominal leak point pressure will be measured by a urodynamic function study	12 weeks
Secondary	Change in urine flow rate	urine flow rate will be measured by urodynamic function a study	12 weeks
Secondary	Change in bladder pressure	bladder pressure will be measured during filling, storage and voiding by urodynamic study	12 weeks
Secondary	Change in post void residual urine volume	post void residual urine volume will be measured using bladder ultrasound	12 weeks
Secondary	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
Secondary	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