Abstract
Objectives
Androgen imbalance is associated with cardiovascular disease risk but the exact impact on lipid and glucose profile is unknown. Finasteride (FIN) prevents the conversion of testosterone to its active metabolite dihydrotestosterone (DHT) by inhibiting the type II 5alpha-reductase. Our objective is to examine the impact of FIN on cardiovascular disease risk. We hypothesize that FIN delays the progression of atherosclerosis by ameliorating hyperglycemia and dyslipidemia.
Methods
We used the low-density lipoprotein receptor (LDLR)-deficient (Ldlr−/−) mouse model as a widely regarded model of atherosclerotic plaque development in rodents. Four-week-old male mice (n = 9–15/group) were fed a Western-diet containing 41% fat +0.3% cholesterol with increasing doses of FIN (10 mg/kg, 100 mg/kg, and 1000 mg/kg diet) for 12 weeks. Littermates fed Western-diet without FIN were used as a control group. A week before tissue harvest, mice were subjected to a glucose tolerance test (GTT). At the
end of the experiment, mice were sacrificed, and their tissue and body weights were analyzed. A total cholesterol assay was performed at 0, 4, 8, and 12 weeks.
Results
We examined prostate size, whose growth is DHT dependent, as an indicator of the effect of finasteride in our experimental model. We observed a dose-dependent effect of FIN on prostate size for all the doses (P < .0001), indicating FIN had a physiological impact on these mice. No changes in food intake or circulating transaminase levels were observed, discarding any evidence of food intolerability or hepatic toxicity. FIN did not alter GTT among experimental groups or any other biometric parameter. However, we observed a significant reduction in body weight gain in the high dose group (P = .0027) in comparison to the other experimental groups. Total cholesterol levels at the time of the sacrifice were significantly reduced in the high dose group (P < .0001) in comparison to the other experimental groups. Future experiments will include atherosclerotic plaque characterization of both size and composition.
Conclusions
Our findings suggest that a high dose of FIN is associated with a reduction of total plasma cholesterol and body weight in Ldlr−/− mice.
Funding Sources
USDA multistate hatch project (W4002)
Finasteride Reduces Total Cholesterol in LDLR-Deficient Mice
