PD27-11 THERAPEUTIC EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Female Incontinence - Therapy I1 Apr 2015PD27-11 THERAPEUTIC EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS Katsumi Kadekawa, Naoki Kawamorita, Philip Turnbull, Alan Russell, Sundeep Chandra, Joanna Barton, and Naoki Yoshimura Katsumi KadekawaKatsumi Kadekawa More articles by this author , Naoki KawamoritaNaoki Kawamorita More articles by this author , Philip TurnbullPhilip Turnbull More articles by this author , Alan RussellAlan Russell More articles by this author , Sundeep ChandraSundeep Chandra More articles by this author , Joanna BartonJoanna Barton More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.455AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although the etiology of stress urinary incontinence (SUI) in women is multifactorial, estrogen deficiency due to menopause is one of the major causes of SUI that induces atrophic and degenerative changes in urethral and pelvic floor muscles. Selective androgen receptor modulators (SARMs) selectively stimulate anabolic pathways of the androgen receptor in muscle and bone while sparing the androgenic effects typically seen with steroidal androgens. In this study, we examined the effect of a SARM (GSK2849466A) on the urethral continence mechanisms in a rat model of SUI induced by bilateral ovariectomy (OVX). METHODS Female nulliparous Sprague-Dawley rats with bilateral OVX were used. Rats were divided into 3 groups; sham operated (sham), vehicle-treated OVX (OVX-V), and GSK2849466A (0.03mg/kg/day, p.o.)-treated OVX (OVX-SARM) groups. At 2 weeks after OVX, vehicle or SARM treatment was started. After 4 weeks of treatment (6 weeks after OVX), rats were subjected to the evaluation of sneeze-induced continence reflex and sneeze-induced leak point pressure (S-LPP) measurements, followed by histological analyses of urethral tissues. RESULTS Urethral baseline pressure (UBP) and the amplitude of urethral responses during sneezing (AURS) were significantly decreased in the OVX-V group (n=11) by 46% and 38%, respectively, compared to the sham group (n=8). In the OVX-SARM group (n=11), UBP and AURS were significantly increased by 64% and 74%, respectively, compared to the OVX-V group. Fluid leakage was observed with S-LPP values of 59.8 □} 9.5 cmH2O during sneezing in all rats of the OVX-V group (n=8) whereas sham rats (n=8) did not leak during sneezing. In the OVX-SARM group (n=8), fluid leakage during sneezing was observed with a higher S-LPP value (82.9 cmH2O) in only 1 out of 8 rats (12.5%). Also, the OVX-SARM group had hypertrophy/reversal of atrophy of striated and smooth muscles in urethral transverse sections, compared to the OVX-V group. CONCLUSIONS These results indicate that ovariectomy significantly impairs urethral continence function after 6 weeks, and that SARM treatment restores the reductions in UBP, AURS and SLPP accompanied with urethral muscle hypertrophy, leading to the prevention of SUI. Based on our previous studies, UBP and AURS parameters are predominantly correlated to urethral smooth and striated muscle activity, respectively. Our current studies show that SARMs could be effective for the treatment of SUI by enhancing smooth and striated muscle mediated urethral function under stress conditions such as sneezing. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e575-e576 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katsumi Kadekawa More articles by this author Naoki Kawamorita More articles by this author Philip Turnbull More articles by this author Alan Russell More articles by this author Sundeep Chandra More articles by this author Joanna Barton More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...