Micturition dysfunction in four-month old ovariectomized rats: Effects of testosterone replacement

摘要

Abstract 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 intramuscular injections of testosterone undecanoate. Cystometric study, and bladder and urethra smooth muscle reactivities 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 II-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 β 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. Highlights ? Four-month old OVX rats proving a suitable experimental model for exploring the lower urinary function after menopause ? Testosterone normalizes micturition dysfunction in 4-month old OVX rats ? Would be clinically relevant to examine testosterone administration in postmenopausal women with urological disorders; or testosterone administration should be examined in postmenopausal women with urological disorders.