Steroid Hormone Receptors as Potential Mediators of the Clinical Effects of Dutasteride: A Prospective, Randomized, Double-Blind Study

Steroid Hormone Receptors as Potential Mediators of the Clinical Effects of Dutasteride: A Prospective, Randomized, Double-Blind Study

Author Alonso, Joao C. C. Google Scholar
Reis, Leonardo O. Google Scholar
Garcia, Patrick V. Google Scholar
Ferreira, Ubirajara Google Scholar
Matheus, Wagner E. Google Scholar
Simoes, Fabiano A. Google Scholar
Rejowski, Ronald F. Google Scholar
Alonso-Vale, Maria Isabel Cardoso Autor UNIFESP Google Scholar
Favaro, Wagner J. Google Scholar
Abstract This study characterizes the clinical and morphofunctional effects of a 5 alpha-reductase inhibitor on steroid hormone receptors in normal human prostate tissue, as potential mediators of the clinical effects of dutasteride. This work was a prospective, double-blind, and randomized study that evaluated 49 men aged between 45 and 70 years, with no alterations in a digital rectal examination and prostate-specific antigen measurements between 2.5 and 4.0 ng/mL. These patients underwent prostate biopsy guided by transretal ultrasound with prostate neoplasia being ruled out, and the patients were divided into two groups, with one group receiving dutasteride (n = 25) and one group receiving a placebo (n = 24). The patients were clinically assessed each quarter, and at the end of 12 months they underwent new laboratory tests, prostate rebiopsy, and histopathological, immunohistochemical and clinical analyses. The estrogen receptor-beta (ER beta) and androgen receptor immunoreactivities were higher, and the proliferation/apoptotic ratio was significantly lower with predominance of the apoptotic process, followed by a significant reduction in the prostate volume and the total serum prostate-specific antigen levels in the dutasteride group when compared with the placebo group, with a clear supremacy of ER beta. There were no significant variations in the serum estrogen and testosterone levels, in the body mass index, or in the ER alpha immunoreactivities in the dutasteride and placebo groups. The results demonstrated the importance of the ER beta pathway in the activation mechanisms of apoptosis, exerting a protective effect in the normal prostate, indicating that this receptor might be an important mediator of the clinical effects of dutasteride.
Keywords prostate
dutasteride
steroid sex hormones
androgen receptor
estrogen receptor
5 alpha-reductase inhibitors
xmlui.dri2xhtml.METS-1.0.item-coverage Thousand Oaks
Language English
Date 2017
Published in American Journal Of Mens Health. Thousand Oaks, v. 11, n. 1, p. 126-133, 2017.
ISSN 1557-9883 (Sherpa/Romeo, impact factor)
Publisher Sage Publications Inc
Extent 126-133
Origin http://dx.doi.org/10.1177/1557988315602961
Access rights Closed access
Type Article
Web of Science ID WOS:000391542300014
URI https://repositorio.unifesp.br/handle/11600/56497

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