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

项目摘要 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妇女，对生活质量产生重大负面影响。应力 尿失禁（SUI）是最常见的尿失禁类型，被定义为不自主尿液的主诉 努力或用力时的渗漏，包括咳嗽、打喷嚏或提起。骨盆底完整性是一个重要的 SUI的预测。骨盆底肌肉系统参与骨盆器官的支撑和排尿。 这些肌肉群的随意收缩使得能够控制尿道括约肌以维持排尿。 在压力演习中受伤。SUI是由于骨盆底肌肉组织、筋膜和 韧带.最近的研究表明，雄激素可能在骨盆底和下 尿道完整性，因为这些结构中的肌肉是雄激素敏感的，并表达大量的 雄激素受体在动物和人类。在临床前模型中， 导致骨盆底肌肉质量比任何其他骨骼肌群更大的增加， 强调了这块肌肉对雄激素的高度敏感性在雌性动物模型中- 诱导SUI，睾酮治疗增加骨盆底肌肉质量，改善尿动力学参数。 对高睾酮水平的多囊卵巢综合征女性的观察性研究显示， 与对照组相比，骨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，睾丸激素对骨盆底肌肉有直接的合成代谢作用， 为患有SUI的女性提供治疗选择。补充睾酮对盆腔组织合成代谢的影响 压力性尿失禁患者的底板肌肉尚未在女性中进行研究。 本提案的总体目标是评估睾酮补充剂在增加 一项在绝经后老年妇女中进行的双盲、随机对照试验， 压力性尿失禁我们还将评估睾酮补充剂对尿动力学的影响 功能、泌尿系统症状和生活质量。我们提出了一个为期12周的双盲，随机对照， 一项确定睾酮补充剂与安慰剂在年龄 60岁及以上压力性尿失禁。将测量以下结果：1）骨盆底 骨盆磁共振成像的肌肉体积，2）尿动力学研究的尿动力学功能，以及 3)泌尿系统症状和生活质量。目前可用于女性SUI的治疗主要集中在外科手术 但是，几乎没有人试图恢复对联合国的有力支持的完整性。因此，有一个明确的 需要创新，为SUI女性提供更广泛的有效治疗选择。如果这次试验 证实了睾酮治疗的好处，女性SUI患者将有一个便宜，相对安全， 易于管理的药物，有可能改变这些患者的护理。

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.