The Anabolic Effect of Testosterone on Pelvic Floor Muscles

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Menopause; Stress Urinary Incontinence
• Intervention / Treatment: Drug: Testosterone cypionate; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Grace Huang, MD; Phone Number: 6175259192; Email: ghuang7@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Testosterone; Testosterone Cypionate 25-mg weekly by intramuscular injection	Drug: Testosterone cypionate; weekly by intramuscular injection
Placebo Comparator: Placebo; Placebo intramuscular injections weekly	Drug: Placebo; weekly by intramuscular injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Grace Huang, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: menopause; pelvic floor disorders; stress urinary incontinence; testosterone therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Incontinence; Enuresis; Urinary Incontinence, Stress; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 2023P002632; R01DK136904 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No