Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment
The World Journal of Men's Health
; : 240-248, 2019.
Article
in En
| WPRIM
| ID: wpr-742353
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Oxidoreductases
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Transforming Growth Factors
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Administration, Oral
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Collagen
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Rats, Sprague-Dawley
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Finasteride
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Models, Animal
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Electric Stimulation
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5-alpha Reductase Inhibitors
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Dutasteride
Type of study:
Prognostic_studies
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
The World Journal of Men's Health
Year:
2019
Type:
Article