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摘要
Aims: Androgen deficiency has been implicated in urological complications of postmenopausal women. This study examined the effects of testosterone replacements on the lower urinary tract dysfunction in 4-month old ovariectomized (OVX) rats. Main methods: Sprague-Dawley female rats were OVX bilaterally. Three months later, rats received single intra-muscular injections of testosterone undecanoate. Cystometric study, and bladder and urethra smooth muscle re activities were evaluated. Key findings: Ovariectomy reduced by 65% (p < 0.05) the serum testosterone levels. Testosterone replacement at 5 mg/kg restored serum hormone levels to baseline, whereas 10 mg/kg produced 14-fold higher testosterone levels. OVX rats exhibited significant increases of body weight, perigonadal fat and blood pressure, and reduced uterus weight, but none of these parameters were changed by testosterone replacements. OVX rats exhibited micturition dysfunction characterized by increases of basal pressure, threshold pressure, voiding frequency and post-voiding pressure. In addition, the bladder contractions induced by electrical-field stimulation (EFS) and carbachol were significantly reduced, whereas angiotensin Il-induced urethral contractions were significantly increased in OVX rats. Testosterone replacement at 10 mg/kg (but not at 5 mg/kg) dose fully normalized the in vivo micturition dysfunction, as well as the in vitro bladder and urethral alterations. Testosterone (10 mg/kg) also significantly potentiated the bladder relaxations induced by the beta(3)-adrenoceptor agonist mirabegron. The protective effects of testosterone were not modified by concomitant treatment with the aromatase inhibitor letrozole (2.5 mg/kg, 4 weeks). Significance: The improvement of micturition dysfunction by testosterone replacement suggests that androgen therapy might be of therapeutic benefit for urological complications associated with post-menopause.
- 出版日期2017-6-15
