Effects of ovariectomy and estrogen replacement on the urethral continence reflex during sneezing in rats.

Abstract

Stress urinary incontinence is often seen in postmenopausal women but limited information is available on hormone dependent changes of urethral function. Thus, we examined how ovariectomy and estrogen replacement affect urethral continence mechanisms. In female nulliparous Sprague-Dawley® rats under urethane anesthesia after ovariectomy with or without estrogen replacement we measured urethral response amplitude during sneezing, urethral baseline pressure and sneeze induced leak point pressure. Whole urethras were tested for ex vivo urethral properties. Urethral response amplitude during sneezing was significantly decreased in 3 and 6-week ovariectomized rats. Urethral baseline pressure was significantly decreased only in 6-week ovariectomized rats. After estrogen replacement urethral baseline pressure but not urethral response amplitude during sneezing was significantly increased. Neither 3-week ovariectomized nor sham operated rats leaked during sneezing but fluid leakage was observed in 63% of 6-week ovariectomized rats. Estrogen replacement decreased the stress urinary incontinence incidence to 25%. Ex vivo testing revealed a significant increase in middle urethral compliance and a decrease in β stiffness at the proximal and middle urethras in 6-week ovariectomized rats. Results indicate that ovariectomy significantly impairs urethral function from the early stage (3 weeks) but does not induce stress urinary incontinence until the late stage (6 weeks). Also, estrogen replacement restores only the urethral baseline pressure parameter, leading to partial prevention of stress urinary incontinence. Since urethral baseline pressure and urethral response amplitude during sneezing parameters are related to urethral smooth and striated muscle activity, respectively, based on our previous studies, hormone replacement therapy may be partially effective for stress urinary incontinence by enhancing smooth muscle mediated urethral activity under stress conditions such as sneezing.