Previous studies showed that capsaicinoid supplementation favorably modifies the plasma lipoprotein profile. The present study investigated the effect of capsaicinoids on plasma lipids and gene expressions of key receptors and enzymes involved in cholesterol metabolism in ovariectomized (OVX) rats. OVX rats were fed with a cholesterol-free diet and orally administered 0 mg kg(-1) bw (OVX-CON), 5 mg kg(-1) bw (OVX-LD), 10 mg kg(-1) bw (OVX-MD), and 15 mg kg(-1) bw (OVX-HD) capsaicinoids daily for 28 days. As the capsaicinoids dose increased, body weight gain and concentrations of plasma triglyceride, total cholesterol, and low-density lipoprotein cholesterol, as well as total lipid accumulation were significantly decreased. In addition, the mRNA levels of hepatic 3-hydroxyl-3-methylglutaryl CoA reductase and cholesterol-7α-hydroxylase were down-regulated, whereas those of transient receptor potential vanilloid type-1, ileal apical sodium-dependent bile acid transporter, and intestinal bile acid binding protein were up-regulated. The excretion of small intestinal bile acid contents and fecal bile acid also decreased. These results suggest that capsaicinoids can prevent ovarian hormone deficiency-induced hypercholesterolemia by inhibiting the hepatic cholesterol synthesis.