TPELVIC: Testosterone Effects on Pelvic Floor Muscles

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04026880

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Urinary Incontinence Menopause	Drug: Testosterone Enanthate Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Arm weekly IM administration of 25 mg Testosterone Enanthate for 12 weeks	Drug: Testosterone Enanthate 25 mg testosterone enanthate administered by intramuscular injection weekly for 12 weeks Other Names: Delatestryl
Placebo Comparator: Control Arm Weekly IM administration of placebo for 12 weeks	Drug: Placebo Placebo administered by intramuscular injection weekly for 12 weeks Other Names: Inactive comparator

Arm

Intervention/Treatment

Active Comparator: Treatment Arm

weekly IM administration of 25 mg Testosterone Enanthate for 12 weeks

Drug: Testosterone Enanthate

25 mg testosterone enanthate administered by intramuscular injection weekly for 12 weeks

Other Names:

Delatestryl

Placebo Comparator: Control Arm

Weekly IM administration of placebo for 12 weeks

Drug: Placebo

Placebo administered by intramuscular injection weekly for 12 weeks

Other Names:

Inactive comparator

Outcome Measures

Primary Outcome Measures

Change in pelvic floor muscle volume [12 weeks]
Pelvic floor muscle volume will be measured by 3-dimensional dynamic pelvic floor magnetic resonance imaging (MRI)

Secondary Outcome Measures

Change in urine volume at first desire to void [12 weeks]
Urine volume at first desire to void will be assessed by cystometry
Change in urine volume at first urge to void [12 weeks]
Urine volume at first urge to void will be assessed by cystometry
Change in maximum cystometric capacity (when the patient feels she can no longer delay micturition) [12 weeks]
Maximum Cystometric Capacity will be assessed by cystometry
Change in urine flow [12 weeks]
Rate of urine flow (urine volume voided over time) will be assessed by Uroflowmetry
Change in urethral sphincter contraction strength [12 weeks]
Strength of urethral sphincter contraction will be assessed by urethral pressure profilometry.
Change in urine leak point pressure [12 weeks]
Urine leak point pressure will be assessed by cystometry
Change in self-reported urinary incontinence [12 weeks]
Urinary Incontinence will be assessed by the Urogenital Distress Inventory (UDI-6 Short Form). The UDI-6 Short Form is a questionnaire with 6 questions that assess the presence and severity of urinary incontinence symptoms. Each question has a potential score of 1 to 4. The final UDI-6 score is calculated by adding all scores as explained above, and dividing the result by 6 to obtain a mean value which is in turn multiplied by 25 to obtain the scale score. The total scaled score can range from 0 to 100, higher scores indicating more severe urinary incontinence, and lower scores indicating less severe urinary incontinence

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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
Poorly controlled diabetes mellitus (hemoglobin A1c greater than 8.0%). Subjects on insulin therapy will be excluded.
Uncontrolled hypertension defined as an average of two blood pressure readings of greater than 160/100
Severe obesity defined as body mass index of greater than 40 kg/m2
Current or recent (last 6 months) users of illicit drugs
Significant liver function abnormalities, defined as SGOT, SGPT or alkaline phosphatase value of greater than 1.5 times the upper limit of normal or serum bilirubin levels of greater than 1.5 mg/dl will be excluded
History of breast, ovarian, or endometrial cancer.
History of hyperandrogenic disorders such as moderate to severe hirsutism and/or acne (by self-report), and polycystic ovary disease. Testosterone administration to these patients may exacerbate the underlying disorder.
Significant acne, defined as grade 3 on Palatsi Acne Scale
Women with a mammogram that requires follow-up every 3-6 months, or those who have any first-degree relatives with breast cancer will be excluded.
Women with history of a major cardiovascular event, including angina, congestive heart failure, cerebral vascular accident or history of myocardial infarction or coronary artery angioplasty or bypass surgery
Other Medications. Women who have received in the preceding three months drugs known to affect testosterone production or metabolism such as ketoconazole, Megace, anabolic/androgenic steroids for 3 weeks or longer will be excluded. Women taking ≥ 7.5 mg of prednisone or equivalent glucocorticoid dosing will be excluded. We will also exclude women who are taking or have taken in the past three months medications that affect sexual function (e.g., spironolactone, GnRH agonists). Women receiving thyroid hormone replacement therapy may participate in the study if they have been on a stable replacement dose of L-thyroxine for at least six months.
Undiagnosed vaginal or vulvar bleeding
Women taking concurrent anticoagulants or how have bleeding disorders
History of deep vein thrombosis, pulmonary embolism, or other thromboembolic disorder
Current enrollment in clinical drug intervention studies in the preceding 90 days
Hematocrit < 30% or >48% (Since hematocrit values can transiently increase as a result of dehydration, and the subjects in this trial are required to come after an overnight fast, hematocrit levels may be repeated once if the investigators determine that the initial elevated hematocrit was influenced by dehydration)
Women who have previously experienced intolerance to testosterone enanthate injections
Unable to undergo MRI of the pelvis (e. g. body containing any metallic medical devices or equipment, including heart pacemakers, metal prostheses, implants or surgical clips, any prior injury from shrapnel or grinding metal, exposure to metallic dusts, metallic shavings or having tattoos containing metallic dyes).