Changes in plasma lipoproteins during various androgen suppression therapies in men with prostatic carcinoma: effects of orchiectomy, estrogen, and combination treatment with luteinizing hormone-releasing hormone agonist and flutamide

Abstract

Cardiovascular complications are a well recognized side-effect of antihormonal therapy in men with prostatic carcinoma. We studied changes in plasma lipoproteins in patients with prostate cancer during treatment with several androgen suppression therapies. Estrogen, orchiectomy, and a combination of LHRH agonist and antiandrogen (flutamide) reduced plasma testosterone concentrations (89-92%) and plasma estradiol decreased by 85%, 44%, and 54%, respectively. Estrogen induced hypertriglyceridemia and elevation of plasma HDL cholesterol, phospholipid, and apolipoprotein A-I and A-II concentrations. Low density lipoprotein (LDL) cholesterol decreased but LDL apolipoprotein B did not. These results suggest that the cardiovascular complications that occur during estrogen administration are not mediated through changes in lipoprotein profile, other than the hypertriglyceridemic effect. Orchiectomy caused hypercholesterolemia and an increase in both total and LDL apolipoprotein B, all of which are strong determinants of cardiovascular disease. The high density lipoprotein (HDL) concentration was not affected despite a reduction in plasma testosterone, perhaps due to a simultaneous decrease in estradiol. Combination therapy had no effect on plasma lipid and apolipoprotein B concentrations, but very low density lipoprotein (VLDL) apolipoprotein B decreased, and LDL apolipoprotein B increased. The HDL cholesterol and apolipoprotein A-I concentrations increased but A-II and phospholipids did not. These results suggest enhanced lipoprotein lipase activity, consistent with the reciprocal changes in VLDL and LDL apolipoprotein B levels, apolipoprotein B enrichment of LDL particles, and increase in HDL cholesterol. The higher apolipoprotein A-I to A-II ratio indicates an increase in HDL2 subfraction due to inhibition of endothelial hepatic lipase, increased secretion of apolipoprotein A-I, or both. These effects are attributed to estradiol, which decreased less than after orchiectomy, and to additional adrenal androgen inhibition by flutamide. We conclude that estradiol plays an important role in determining plasma lipoprotein concentrations in men, and androgens exert an antagonist effect. The lipoprotein profile resulting from the combination treatment is more beneficial than that resulting from orchiectomy or estrogen administration.