Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment

Abstract

Purpose: The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was asso-ciated with higher rate of permanent erectile dysfunction (ED) in a rat model. Materials and Methods: Male Sprague-Dawley rats (n=76) were assigned to five groups: (i) normal control group; (ii) dutaste-ride (0.5 mg/rat/d) for 4-weeks group; (iii) dutasteride for 4-weeks plus 2-weeks of resting group; (iv) dutasteride for 8-weeks group; and (v) dutasteride for 8-weeks plus 2-weeks of resting group. In vivo erectile responses to electrical stimulation, and changes of fibrotic factors and smooth muscle/collagen contents in the corpus cavernosum were evaluated in each group. Results: Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period. Conclusions: Our study showed that recovery from ED depended on the duration of medication, and administration of dutas-teride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.

Keywords

• 5-alpha reductase inhibitors
• Dutasteride
• Erectile dysfunction
• Finasteride