The Anabolic Effect of Testosterone on Pelvic Floor Muscles

Mass General Brigham

Status and phase: Not yet enrolling; Phase 2

Conditions: Menopause; Stress Urinary Incontinence

Treatments: Drug: Testosterone cypionate; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06111209

2023P002632

R01DK136904 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 30 estimated patients

Sex: Female

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups, including a placebo group

Testosterone

Active Comparator group

Description:

Testosterone Cypionate 25-mg weekly by intramuscular injection

Treatment:

Drug: Testosterone cypionate

Placebo

Placebo Comparator group

Description:

Placebo intramuscular injections weekly

Treatment:

Drug: Placebo