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. However, the effect of testosterone deficiency on bladder and urinary function has not yet been elucidated. Therefore, we aimed to elucidate the effect of testosterone on bladder function in castrated rats using pharmacological and molecular biological techniques.

We divided sexually mature 12-week-old male Wistar-ST rats into into the following groups: castrated (Cast), castrated with testosterone (Cast+T), and sham (Sham). Testosterone was administered with silastic tubing at 3 months after the castration. After 4 months, voiding function and detrusor muscle contraction were evaluated. Cystometrography (CMG) was performed to assess the voiding interval and intravesical pressure. Detrusor muscle contraction was measured by isometric tension using bladder tissue. Contraction was induced by carbachol and electrical field stimulation (EFS). Moreover, a muscarinic receptor antagonist was used. Real-time PCR was used to examine variations in the expression of mRNA in the excised bladder tissue.

Based on the CMG (80 μL/min) results, castration did not significantly affect the voiding interval (Cast group: 653.3 ± 145.7 seconds, Sham group: 767.7 ± 233.2 seconds Cast+T group: 955.0 ± 109.6 seconds). Intravesical pressure was also not significantly different between groups. On the other hand, castrated rats showed significantly weaker contractile force of the detrusor muscle in response to carbachol (Cast group: 61.9 ± 15.4 N/g, Sham group: 220.6 ± 62.4 N/g). Testosterone administration significantly increased the response (Cast+T group: 104.8 ± 7.5 N/g). Similarly, castrated rats showed weaker contractile force against EFS (Cast group: 73.0 ± 19.0 N/g, Sham group: 183.6 ± 26.4 N/g, Figure A) and testosterone administration significantly increased the force (Cast+T group: 150.8 ± 3.7 N/g). The addition of atropine decreased the contractile response. The addition of the atropine eliminated the differences between the groups (Figure B). After a muscarinic receptor antagonist was added, the contractile force against EFS was not significantly different between the Sham and Cast groups. Muscarinic receptor (M2 and M3) mRNA expression was significantly lower in the Cast group than in the Sham group (Figure C-D). Testosterone administration significantly increased the mRNA expressions.

CMG did not reveal a difference in the urinary function of sham-operated and castrated rats 4 months after castration. On the other hand, weaker detrusor muscle contraction force by carbachol and EFS was observed in castrated rats. The inhibited muscarinic receptor and real-time PCR results showed that testosterone deficiency decreased urinary bladder smooth muscle contractile response through muscarinic receptors. However, testosterone administration improved the detrusor muscle contraction force by carbachol and EFS and the urinary bladder smooth muscle contractile response.

Testosterone deficiency might cause an under active bladder by decreasing the response of the muscarinic receptors and urinary bladder smooth muscle contractility. Testosterone administration might improve the under active bladder induced by testosterone deficiency.