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.

项目概要 包括尿失禁 (UI) 在内的女性盆底疾病 (PFD) 是一个主要的公共卫生问题 影响美国所有年龄段的女性，对生活质量产生重大负面影响。压力 尿失禁 (SUI) 是最常见的 UI 类型，被定义为不自主排尿的主诉 因用力或用力（包括咳嗽、打喷嚏或举重物）而泄漏。盆底完整性很重要 SUI 的预测因子。盆底肌肉组织参与支持盆腔器官和排尿。 这些肌肉群的自主收缩能够控制尿道括约肌以维持排尿 压力动作期间的节制。 SUI 是由于骨盆底肌肉组织、筋膜和肌肉无力所致 韧带。最近的研究表明，雄激素可能在盆底和下腹部发挥着重要作用。 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 动物和人类体内的雄激素受体。在临床前模型中，外源睾酮给药 与任何其他骨骼肌群相比，盆底肌肉质量有更大的增加， 强调这块肌肉对雄激素的高度敏感性。在实验的雌性动物模型中 诱发 SUI，睾酮治疗可增加盆底肌肉质量并改善尿动力学参数。 对睾酮水平较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，盆底肌肉质量和力量更大，UI 症状更少。采取 总之，这些数据表明睾酮对盆底肌肉有直接的合成代谢作用，这可能 为患有 SUI 的女性提供一种治疗选择。补充睾酮对骨盆合成代谢的影响 尚未对女性压力性尿失禁患者的底肌进行研究。 该提案的总体目标是评估补充睾酮在增加睾酮水平方面的功效。 一项针对患有以下疾病的老年绝经后女性的双盲、随机对照试验对骨盆底肌肉的影响 压力性尿失禁。我们还将评估补充睾酮对尿动力学的功效 功能、泌尿系统症状和生活质量。我们建议进行为期 12 周的双盲、随机对照试验 概念验证试验，以确定睾酮补充剂与安慰剂对女性年龄的疗效 60岁及以上患有压力性尿失禁的人。将测量以下结果：1）骨盆底 通过骨盆磁共振成像确定肌肉体积，2) 通过尿动力学研究确定尿动力学功能，以及 3）泌尿系统症状和生活质量。目前女性 SUI 中心可用的治疗方法主要是手术 干预措施很少试图恢复节制动态支持的完整性。因此，有一个明确的 需要创新为患有 SUI 的女性提供更广泛的有效治疗选择。如果这次审判 证实了睾酮治疗的益处，患有 SUI 的女性患者将获得一种廉价、相对安全和 易于管理的现有药物有可能改变这些患者的护理。