A Pilot Study To Evaluate The Effect of Testosterone Enanthate On Structural and Functional Characteristics of Pelvic Floor Muscles In Postmenopausal Women With Urinary Incontinence
Overview
- Phase
- Phase 3
- Intervention
- Testosterone Enanthate
- Conditions
- Urinary Incontinence
- Sponsor
- Brigham and Women's Hospital
- Primary Endpoint
- Change in pelvic floor muscle volume
- Status
- Withdrawn
- Last Updated
- 3 years ago
Overview
Brief Summary
An proof-of-concept study to determine whether administration of testosterone enanthate weekly results in greater improvements in structural and functional characteristics of pelvic floor muscles and urodynamic parameters in postmenopausal women with urinary incontinence than that associated with placebo administration
Detailed Description
Androgen therapy has been widely promoted in women with low serum testosterone levels for the treatment of sexual dysfunction and also for potentially improving body composition, muscle performance, bone mineral density and cognition. Androgens are known to exert direct anabolic effects on skeletal muscle. Testosterone supplementation results in dose-dependent increases in both muscle mass and strength in men. Similarly, our group has also demonstrated that 24-weeks of testosterone administration in hysterectomized women with low testosterone levels was associated with dose and concentration-dependent gains in lean body mass, chest-press power and loaded stair-climb power. Given that androgen receptors have been shown to be expressed throughout the pelvic floor and lower urinary tract, the anabolic effects of androgens on pelvic floor muscles and urethral sphincter may provide a therapeutic option in women with urinary incontinence. In spite of the recognition of the important role of androgens in regulation of pelvic floor muscle mass and function, no randomized trials of the effects of testosterone or selective androgen receptor modulators have been published. Towards our long-term goal of conducting such a randomized efficacy trial of the effect of androgens in women with urinary incontinence, this initial pilot study will provide important data as a proof-of-the concept that the mass and function of levator ani and other pelvic floor muscles can be increased meaningfully by administration of testosterone, and that the increase in the mass and function of pelvic floor muscles will be associated with significant improvements in urodynamic parameters. Although MRI has been used clinically to evaluate pelvic floor anatomy, dynamic MRI of the pelvic floor muscles coupled with urodynamic studies has not been standardized previously; an important aim of this pilot study is to optimize the procedures for dynamic MR imaging of the pelvic floor structures and couple them with evaluation of urodynamics of the urinary bladder, bladder sphincter, and the urethra. Furthermore, the preliminary estimates of effect size and variance generated in this pilot study will guide the estimates of sample size and statistical power in subsequent larger randomized efficacy trials of androgens in women with urinary incontinence.
Investigators
Grace Huang
Principal Investigator
Brigham and Women's Hospital
Eligibility Criteria
Inclusion Criteria
- •Medically stable, ambulatory, postmenopausal women, 60 years of age or older
- •A normal mammogram in the preceding 12 months of study entry will be required. Women will be asked to either provide documentation of their last mammogram results or, with their permission, sign a medical release form to allow us to obtain the results of their last mammogram.
- •Able to give informed consent
- •Women with either stress urinary incontinence, or mixed urinary incontinence (stress and urgency)
Exclusion Criteria
- •Women with endometrial stripe \>4 mm on pelvic ultrasound
- •≥ 1 first-degree relative with breast cancer
- •Previous pelvic surgery (ie. hysterectomy)
- •Women with history of radiation treatment to the pelvis
- •Any neurologic disorder causing urinary incontinence or bladder dysfunction (ie. multiple sclerosis)
- •Estrogen therapy currently or in the past 3 months
- •Women who have been diagnosed with major psychoses or bipolar disorders and/or untreated depression
- •Women with severe depression and/or severe anxiety as measured by the Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory (BAI), respectively
- •Any acute or subacute illness that required hospitalization in the last three months
- •Cancers that require active therapy (not in remission for at least two years) including those with a life expectancy less than 5 years
Arms & Interventions
Treatment Arm
weekly IM administration of 25 mg Testosterone Enanthate for 12 weeks
Intervention: Testosterone Enanthate
Control Arm
Weekly IM administration of placebo for 12 weeks
Intervention: Placebo
Outcomes
Primary Outcomes
Change in pelvic floor muscle volume
Time Frame: 12 weeks
Pelvic floor muscle volume will be measured by 3-dimensional dynamic pelvic floor magnetic resonance imaging (MRI)
Secondary Outcomes
- Change in urine flow(12 weeks)
- Change in urethral sphincter contraction strength(12 weeks)
- Change in urine volume at first desire to void(12 weeks)
- Change in urine volume at first urge to void(12 weeks)
- Change in maximum cystometric capacity (when the patient feels she can no longer delay micturition)(12 weeks)
- Change in urine leak point pressure(12 weeks)
- Change in self-reported urinary incontinence(12 weeks)