Incomplete recovery of erectile function in rat after discontinuation of dual 5-alpha reductase inhibitor therapy.

J Sex Med. 2012 Jul;9(7):1773-81. doi: 10.1111/j.1743-6109.2012.02759.x. Epub 2012 May 8.
Incomplete recovery of erectile function in rat after discontinuation of dual 5-alpha reductase inhibitor therapy.
Oztekin CV, Gur S, Abdulkadir NA, Lokman U, Akdemir AÖ, Cetinkaya M, Hellstrom WJ.

Department of Urology, Ankara Numune Education and Research Hospital, Ankara, Turkey.

AIM:
The association of 5-alpha reductase inhibitor (5ARI) therapy and sexual dysfunction has been reported. Some patients claim persistent erectile dysfunction despite long-term discontinuation of 5ARI treatment. The aim of this study was to assess erectile function after cessation of 5ARI therapy using a rat model.
METHODS:
Twenty-six adult male Sprague-Dawley rats were randomized into three groups: (i) control (N = 10); (ii) 8-week dutasteride treatment (0.5 mg/rat/day, in drinking water, N = ; and (iii) 6-week dutasteride treatment followed by a 2-week washout period (N = . The experiments were performed after 8 weeks from the initiation of treatment in all groups. In vivo erectile activity and in vitro contractile and relaxant responses of cavernosal smooth muscle were investigated.
RESULTS:
In vivo erectile activity (intracavernosal pressure [ICP]/mean arterial pressure [MAP] and total ICP) in treatment groups were significantly decreased compared with controls (ICP/MAP: P < 0.001 for 2.5 v, 5 v, and 7.5 v; total ICP: P < 0.001 for 5 v and P < 0.01 for 7.5 v). Acetylcholine-induced relaxations were diminished in treatment groups (P < 0.05). Relaxant responses to electrical field stimulation (EFS) were decreased in the 8-week treatment group (P < 0.05) but were similar to controls in the washout group. Sodium nitroprusside (SNP)-induced endothelium-independent relaxations were reduced in the 8-week dutasteride treatment group (P < 0.01), while these responses were restored in the washout group. The contractile responses to the alpha1-adrenergic agonist phenylephrine were decreased in treatment groups compared with controls (P < 0.01). Direct neurogenic contractile responses in the dutasteride groups were significantly lower than controls between 1 and 15 Hz frequencies (but not at 20 Hz) and washout partially restored the responses at 10 and 15 Hz.
CONCLUSION:
Discontinuation of dutasteride improved the relaxant responses to EFS and SNP, while cholinergic and adrenergic responses remained depressed. Our findings suggest a time-dependent detriment of dutasteride on erectile function. The withdrawal/washout effect of 5ARIs on parameters of human sexual function warrants further investigation.