Ezetimibe reduces enlarged prostate in an animal model of benign prostatic hyperplasia.
OBJECTIVE
Benign prostatic hyperplasia is a common urinary tract disorder that affects aging men. The molecular mechanisms underlying benign prostatic hyperplasia are obscure and the development of animal models to test novel treatment strategies is challenging. We report that the Bio 87.20 hamster strain (Bio Breeders, Watertown, Massachusetts) shows 5α-reductase-sensitive prostate enlargement and a decrease in circulating cholesterol reduces prostate size.


METHODS
Bio 87.20 hamsters 17 months old with an enlarged prostate were fed a diet containing no or minimal cholesterol and including finasteride (Merck, Whitehouse Station, New Jersey) and/or ezetimibe (Schering-Plough, Kenilworth, New Jersey) for 4 months. The prostate complex was removed, volume and weight were determined, and tissue was examined histologically.


RESULTS
Prostate enlargement depended on cholesterol in the diet. Blockade of intestinal cholesterol transport with ezetimibe induced prostate regression to a similar extent as the 5α-reductase inhibitor finasteride, a compound used to treat benign prostatic hyperplasia in humans. Histological analysis indicated that finasteride induced widespread prostatic atrophy but normal glandular architecture was preserved in the ezetimibe cohort.


CONCLUSIONS
Results indicate that dysregulation of cholesterol metabolism may be a component of benign prostatic hyperplasia and ezetimibe may be effective as an alternative or adjunct to standard treatment. Our findings also show that the Bio 87.20 hamster is a suitable model for preclinical evaluation of novel benign prostatic hyperplasia therapy.
Pelton
Kristine
K
Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA.
Di Vizio
Dolores
D
Insabato
Luigi
L
Schaffner
Carl P
CP
Freeman
Michael R
MR
Solomon
Keith R
KR
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D006224:Cricetinae; D004195:Disease Models, Animal; D000069438:Ezetimibe; D008297:Male; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology
D000924:Anticholesteremic Agents; D001384:Azetidines; D000069438:Ezetimibe