Decreased testosterone in elderly men is known to result in a variety of physical symptoms. According to the clinical practice guidelines for male lower urinary tract symptoms, 41.9% of elderly men who do not have lower urinary tract obstruction but have lower urinary tract symptoms have been reported to have detrusor contractile dysfunction. This study reported that the urinary bladder smooth muscle contractile response of castrated rats decreased by decreasing the response of the muscarinic receptors in ICS2020. Moreover, testosterone administration may also improve the detrusor muscle contraction force. However, the prostate was changed with testosterone levels. This study investigated the direct effect of testosterone on voiding function using female rats.

Eight-week-old female Wistar–ST rats were divided into the ovariectomy (OVX) and OVX with testosterone (OVX + T). Testosterone undecanoate (25 mg/kg) was administered 1 month after OVX. The voiding function was evaluated after 4 months. Moreover, a cystometrography (CMG) was performed to assess the voiding interval and intravesical pressure. Real-time polymerase chain reaction (PCR) was used to examine variations in the mRNA expression in the excised bladder tissue.

Based on the CMG (80 μL/min) results, testosterone administration significantly prolonged the voiding interval (OVX group, 951.3 ± 146.0 s; OVX + T group, 1,905.8 ± 255.9 s; p < 0.05). Similarly, testosterone administration significantly increased one-time voiding volume (OVX group, 1.03 ± 0.19 g; OVX + T group, 2.04 ± 0.27 g; p < 0.05). Moreover, intravesical pressure was not significantly different between the groups (OVX group, 43.6 ± 3.2 cmH2O; OVX + T group, 41.3 ± 2.9 cmH2O; p > 0.05). 
Epithelial sodium channel (ENaC-α, β, and γ) mRNA expression was significantly lower in the OVX + T group than in the OVX group (p < 0.05) based on real-time PCR analysis. Testosterone administration also decreased transient receptor potential cation channel (TRPV-4) mRNA expression (p < 0.05). Furthermore, muscarinic receptor (M2 and M3) mRNA expression was not significantly changed between the groups (p > 0.05).

Testosterone administration may prolong the micturition interval in rats, which may be due to the decrease in the expression level of mechanoreceptors (e.g., ENaC and TRPV-4). Furthermore, the altered muscarinic receptor was not affected in male rats, which may be due to the increase or decrease in the prostate.

Testosterone replacement therapy may be expected as a treatment for urinary symptoms, although it is known that the number of patients with overactive bladder increases with aging.