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 wit...