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Old 02-05-2020, 03:30 PM
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rss Effects of a Selective Androgen Receptor Modulator (SARM), GSK2849446A, on Stress Uri

Related Articles Effects of a Selective Androgen Receptor Modulator (SARM), GSK2849446A, on Stress Urinary Incontinence and Bladder Activity in Rats with Ovariectomy-induced Estrogen Deficiency.

BJU Int. 2020 Feb 03;:

Authors: Kadekawa K, Kawamorita N, Shimizu T, Kurobe M, Turnbull PS, Chandra S, Kambara T, Barton JC, Russell AJ, Yoshimura N

Abstract
OBJECTIVES: To report the effect of a Selective androgen receptor modulators (SARMs) on the urethral continence mechanisms in a rat model of stress urinary incontinence (SUI) induced by bilateral ovariectomy (OVX).
MATERIALS AND METHODS: Female Sprague-Dawley rats with bilateral OVX were used. Rats were divided into 5 groups; sham operated, vehicle-treated OVX, low-dose SARM treated OVX (GSK2849466A: 0.005 mg/kg/day, p.o.), high-dose SARM treated OVX (GSK2849466A: 0.03 mg/kg/day, p.o.) and dihydrotestosterone (DHT) treated OVX (1 mg/kg/day, s.c.) groups. After 4 weeks of SARM treatments or 3 weeks of DHT treatment (6 weeks after OVX), rats were subjected to evaluation of the sneeze-induced continence reflex using microtransducer-tipped catheter methods, sneeze-induced leak point pressure (S-LPP) and continuous cystometry measurements, following by histological analyses of urethral tissues.
RESULTS: (1) OVX significantly impaired urethral continence function after 6 weeks to induce SUI during sneezing. (2) Low-dose SARM treatment restored urethral baseline pressure (UBP) without affecting the amplitude of urethral response during sneezing (A-URS), partially reversing OVX-induced SUI during sneezing. (3) High-dose SARM treatment reversed decreases in both UBP and A-URS, more effectively preventing SUI during sneezing. (4) DHT treatment, only restored A-URS without affecting UBP, partially preventing OVX-induced SUI during sneezing. (5) The high-dose SARM treatment induced hypertrophy of the striated and smooth muscle around the urethra. (6) SARM treatment did not affect bladder function in sham or OVX rats.
CONCLUSION: Treatment with SARMs could be a more effective modality for the treatment of SUI than DHT without affecting bladder function by enhancing smooth and striated muscle mediated urethral function under stress conditions such as sneezing.


PMID: 32011085 [PubMed - as supplied by publisher]



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