Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment
- Author:
Hyun Hwan SUNG
1
;
Jiwoong YU
;
Su Jeong KANG
;
Mee Ree CHAE
;
Insuk SO
;
Jong Kwan PARK
;
Sung Won LEE
Author Information
- Publication Type:Original Article
- Keywords: 5-alpha reductase inhibitors; Dutasteride; Erectile dysfunction; Finasteride
- MeSH: 5-alpha Reductase Inhibitors; Administration, Oral; Animals; Collagen; Dutasteride; Electric Stimulation; Erectile Dysfunction; Finasteride; Humans; Male; Models, Animal; Muscle, Smooth; Oxidoreductases; Rats; Rats, Sprague-Dawley; Transforming Growth Factors
- From:The World Journal of Men's Health 2019;37(2):240-248
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was associated 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) dutasteride (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 dutasteride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.
