Abstract
The cholesterol synthesis-suppressing activity of simvastatin was investigated to determine its clinical efficacy and effects on steroid hormones in type II hyperlipidemic patients. The patients were seven outpatients, and all were postmenopausal females with a mean age of 69.9 years (60-82 years). Simvastatin was administered once every day for 12 months. The daily dosage was 2.5mg in the first 6 months, 5.0mg in the following 4 months and 2.5mg in the last 2 months. The preadministration total cholesterol level in their plasma was 254.4±8.8mg/dl (mean±S. E.). During the 2.5mg administration periods, the total cholesterol and LDL-cholesterol decreased by 13.9±2.7% and 23.4±3.4% (p<0.01), while they decreased by 20.3±3.1% and 29.1±3.9% (p<0.01), respectively, in the 5.0mg administration period. These decreases were dependent on the simvastatin dosage (p<0.01). The HDL-cholesterol level did not change, the HDL-phospholipids level tended to increase, and the HDL-triglycerides level showed a clear increase. The ratio of the LDL-cholesterol to HDL-cholesterol decreased. The apo A-I and apo A-II increased in the early stages of simvastatin administration. Both the apo B and apo E decreased. From among the steroid hormones, cortisol, testosterone, estrediol, progesterone and aldosterone were measured. Simvastatin did not exert any influence on those steroid hormones, except aldosterone, which decreased significantly from the 9th month of administration. The aldosterone level decreased by 31.8±9.0% (p<0.05), from a preadministration level of 111.6±12.0pg/ml to 76.3±14.4pg/ml after 12 months of administration. No changes were detected in the ACTH level or in the plasma renin activity. Although there were no adverse reactions, the diastolic blood pressure slightly, but significantly decreased. This decrease in diastolic pressure dependended on the simvastatin dosage. These results indicate that simvastatin should be clinically effective in treating hypercholesterolemia. The increase in the HDL-triglycerides level suggests that HDL-cholesterol had been reverse-transferred to LDL. Although the observed decreases in the aldosterone level and the blood pressure are desirable phenomena, it is necessary to elucidate the long-term effects of simvastatin on steroid hormones.
