Abstract
This study aimed to assess the structural response of the normal prostate during its recovery following dutasteride discontinuation, either abruptly or gradually, in short-term or long-term treated rats. Fifty-six adult male Wistar rats were randomly allocated into seven groups: a control group and two dutasteride-treated groups (for 4 or 8 weeks, 0.5 mg/kg/day, orally). Furthermore, each corresponding group of the 4- and 8-week groups was subjected to abrupt or tapered drug discontinuation. At the end, blood samples were withdrawn for testosterone (T) and dihydrotestosterone (DHT) analyses. Ventral prostates (VP) were resected and subjected to hematoxylin and eosin (H&E) and Masson trichrome (MTC) staining. Besides, polymerase chain reaction (PCR) analysis and immunohistochemical identification of proliferating cell nuclear antigen (PCNA), caspase-3, and androgen receptors (AR) were performed. After 4 and 8 weeks of treatment, VP showed acinar trophic changes with reduced epithelial thickness in H&E, increased Masson-stained collagen distribution area, suppression of proliferation marker PCNA, activation of apoptosis, and AR downregulation. Discontinuation of dutasteride, whether abruptly or gradually, after short-term treatment showed prostate re-expansion and proliferation in both designs of withdrawal. However, in long-term dutasteride-treated rats, tapered discontinuation maintained the attained atrophic changes provoked in the prostate versus abrupt discontinuation. Abrupt discontinuation was associated with enhanced AR expression coupled with prostate proliferation and caspase-3 downregulation, leading to marked prostate rebound. As a preclinical study, it was concluded that the duration of exposure and the discontinuation design, whether abrupt or tapered, were found to have an impact on the prostate's recovery following dutasteride cessation. Abrupt discontinuation was linked to structural prostate rebound, which may be explained by AR upregulation.