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

评估睾酮对患有压力性尿失禁的老年女性盆底肌肉合成代谢影响的初步研究

• 批准号: 10716432
• 负责人: Grace Huang
• 金额: $ 35.48万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-22 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716432
• 关键词: Affect; Age; Aging; Anabolic Agents; Androgen Receptor; Androgen Therapy; Androgens; Animals; Area; Bladder; Bladder Control; Body Composition; Clinical Trials; Coughing; Data; Development; Disease; Distress; Dose; Double-Blind Method; Elderly; Electromyography; Equipment and supply inventories; Exertion; Experimental Animal Model; Experimental Models; Extravasation; Fascia; Female; Foundations; Functional disorder; Genitourinary system; Goals; Health; Hormonal; Hormonal Change; Human; Incontinence; Intervention; Intra-abdominal; Lifting; Ligaments; Lower urinary tract; Magnetic Resonance Imaging; Measures; Menopause; Mission; Muscle; Muscle Contraction; Observational Study; Operative Surgical Procedures; Organ; Outcome; Patient Care; Patient Self-Report; Patients; Pelvic Floor Disorders; Pelvic Floor Muscle; Pelvic floor structure; Pelvis; Performance; Physical Function; Pilot Projects; Placebo Control; Placebos; Play; Polycystic Ovary Syndrome; Postmenopause; Pre-Clinical Model; Prevalence; Public Health; Quality of Life Assessment; Quality of life; Questionnaires; Randomized; Randomized, Controlled Trials; Role; Sexual Dysfunction; Skeletal Muscle; Sneezing; Sphincter; Stress; Stress Urinary Incontinence; Structure; Supplementation; Symptoms; Testing; Testosterone; Therapeutic; Training; United States; Urethra; Urethral sphincter; Urinary Incontinence; Urinary tract; Urination; Urine; Urodynamics; Woman; abdominal pressure; androgen sensitive; clinical practice; comparative efficacy; comparison control; effective therapy; efficacy evaluation; improved; incontinence symptom; indexing; innovation; lean body mass; levator ani muscle; medication administration; muscle form; muscle strength; older women; pilot trial; pre-clinical; pressure; randomized trial; recruit; response; urinary

PROJECT SUMMARY Female pelvic floor disorders (PFD) which include urinary incontinence (UI) are a major public health problem affecting women of all ages in the United States with significant negative impact on quality of life. Stress urinary incontinence (SUI), the most common type of UI, is defined as the complaint of involuntary urine leakage on effort or exertion, including coughing, sneezing or lifting. Pelvic floor integrity is an important predictor of SUI. The pelvic floor musculature is involved in the support of pelvic organs and micturition. Voluntary contractions of these muscle groups enable control of the urethral sphincter to maintain urinary continence during stress maneuvers. SUI results from weakness of the pelvic floor musculature, fascia and ligaments. Recent studies have shown that androgens may play an important role in pelvic floor and lower urinary tract integrity, as the muscles in these structures are androgen-sensitive and express large numbers of androgen receptors in both animals and humans. In preclinical models, exogenous testosterone administration results in greater increases in pelvic floor muscle mass compared to any other skeletal muscle group, underscoring the high sensitivity of this muscle to androgens. In female animal models of experimentally- induced SUI, testosterone therapy increases pelvic floor muscle mass and improves urodynamic parameters. Observational studies in women with polycystic ovary syndrome who have high testosterone levels show both greater pelvic floor muscle mass and strength as well as fewer UI symptoms compared to controls. Taken together, these data suggest that testosterone has direct anabolic effects on pelvic floor muscles which may provide a therapeutic option in women with SUI. The anabolic effect of testosterone supplementation on pelvic floor muscles in patients with stress urinary incontinence has not been studied in women. The overall goal of this proposal is to evaluate the efficacy of testosterone supplementation in increasing the muscles of the pelvic floor in a double-blind, randomized-controlled trial in older postmenopausal women with stress urinary incontinence. We will also assess the efficacy of testosterone supplementation on urodynamic function, urinary symptoms and quality of life. We propose a 12-week double-blind, randomized-controlled, proof-of-concept trial to determine the efficacy of testosterone supplementation versus placebo in women age 60 years and older with stress urinary incontinence. The following outcomes will be measured: 1) pelvic floor muscle volume with pelvic magnetic resonance imaging, 2) urodynamic function with urodynamic studies, and 3) urinary symptoms and quality of life. Current treatments available for female SUI center largely on surgical interventions and few seek to restore integrity to the dynamic supports of continence. Thus, there is a clear need for innovation to provide a wider range of effective treatment options for women with SUI. If this trial confirms benefits of testosterone therapy, female patients with SUI will have an inexpensive, relatively safe and easy to administer medication available that has the potential to transform the care of these patients.

项目摘要 包括尿失禁（UI）的女性骨盆底障碍（PFD）是一个主要的公共卫生问题 影响美国各个年龄段的妇女，对生活质量产生重大负面影响。压力 尿失禁（SUI），最常见的UI类型，被定义为非自愿尿液的投诉 努力或努力泄漏，包括咳嗽，打喷嚏或举重。骨盆底完整性很重要 SUI的预测指标。骨盆底肌肉与骨盆器官和排尿有关。 这些肌肉组的自愿收缩使能够控制尿道括约肌 压力演习期间的延续性。 SUI是由于骨盆底肌肉，筋膜和 韧带。最近的研究表明，雄激素可能在骨盆底和较低的 尿路完整性，因为这些结构中的肌肉对雄激素敏感，并表达大量 动物和人类的雄激素受体。在临床前模型中，外源睾丸激素给药 与任何其他骨骼肌群相比 强调这种肌肉对雄激素的高灵敏度。在实验的女性动物模型中 诱导的SUI，睾丸激素疗法会增加骨盆底肌肉质量并改善尿动力学参数。 睾丸激素水平高的多囊卵巢综合征女性的观察性研究表明 与对照组相比，与对照组相比，骨盆底肌肉质量和强度以及更少的UI症状。拍摄 总之，这些数据表明睾丸激素对骨盆底肌有直接的合成代谢作用，这可能 提供SUI女性的治疗选择。补充睾丸激素对骨盆的合成代谢作用 尚未在女性中研究压力尿失禁患者的地板肌肉。 该提案的总体目标是评估补充睾丸激素在增加睾丸激素方面的功效 骨盆底的肌肉是在年龄较大的绝经后妇女的双盲，随机控制的试验中 压力尿失禁。我们还将评估补充睾丸激素对尿动力学的功效 功能，尿症状和生活质量。我们提出了一个为期12周的双盲，随机控制的， 概念验证试验，以确定补充睾丸激素与安慰剂在女性年龄的疗效 60岁以上的压力尿失禁。将测量以下结果：1）骨盆底 带有骨盆磁共振成像的肌肉体积，2）尿动力学研究和尿动力学功能， 3）尿症状和生活质量。目前可用于女性SUI中心的治疗 干预措施，很少有人试图将诚信恢复到持续性的动态支持。因此，有一个清晰的 需要创新，为SUI女性提供更广泛的有效治疗选择。如果此试验 确认睾丸激素治疗的好处，SUI女性患者将具有廉价，相对安全且 易于使用的药物有可能改变这些患者的护理。