Cholesterol and benign prostate disease

Abstract

The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept.

Figure 1

A. Effects of ezetimibe (Zetia) and finasteride on prostate size (volume) in the Syrian 87.20 hamster strain, which shows spontaneous, age-dependent prostate enlargement. Data are presented as mean prostate volume (mm³) vs. drug group ± SD. *p<0.05, **p<0.01 (Students t test) n=4/group. Zetia was as effective as finasteride at reversing prostate enlargement in this model. B. Representative micrographs of hamster prostate frozen sections reveal that finasteride induced prostatic epithelial atrophy, while Zetia did not produce a discernible effect on the prostate epithelium. These data were originally reported in Pelton et al. Used with permission.

Figure 1

A. Effects of ezetimibe (Zetia) and finasteride on prostate size (volume) in the Syrian 87.20 hamster strain, which shows spontaneous, age-dependent prostate enlargement. Data are presented as mean prostate volume (mm³) vs. drug group ± SD. *p<0.05, **p<0.01 (Students t test) n=4/group. Zetia was as effective as finasteride at reversing prostate enlargement in this model. B. Representative micrographs of hamster prostate frozen sections reveal that finasteride induced prostatic epithelial atrophy, while Zetia did not produce a discernible effect on the prostate epithelium. These data were originally reported in Pelton et al. Used with permission.