HIGH-DENSITY-LIPOPROTEIN RESPONSE TO 5-ALPHA-DIHYDROTESTOSTERONE AND TESTOSTERONE IN MACACA-FASCICULARIS - A HORMONE-RESPONSIVE PRIMATE MODEL FOR THE STUDY OF ATHEROSCLEROSIS

A decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease, occurs during puberty in males. Previous studies have shown this decrease with testosterone (T) therapy for adolescent males, but the mechanism of this effect is unknown and has not been studied in a non-human primate. Two adult male monkeys (Macaca fascicularis) were studied to determine simultaneous changes in plasma androgens and HDL-C during the phases precastration (Ci); postcastration (Cx); Cx and T therapy; Cx and dihydrotestosterone (DHT) therapy; and T and 5-α-reductase inhibitor therapy (4-MA). After castration, the HDL-C concentrations increased significantly in both animals (monkey A, 57.0 ± 1.8 mg/dL SE to 66.6 ± 2.2, P < .005; monkey B, 62.9 ± 1.6 to 80.2 ± 1.7, P < .001). T-propionate treatment produced a significant decrease in HDL-C (monkey A, 48.0 ± 5.0, P < .01; monkey B, 43.5 ± 0.5, P < .001), which was similar to HDL-C reductions seen when treated with a nonaromatizeable androgen, DHT-propionate (monkey A, 47.5 ± 1.5, P < .005; monkey B, 44.5 ± 3.5, P < .001). T and the 5-α-reductase inhibitor therapy did not increase HDL-C from the levels with T therapy alone (monkey A, 55.7 ± 1.9, NS; monkey B, 57.3 ± 0.3, NS). This study describes for the first time the features of a primate model that is potentially useful for further study of hormone-lipoprotein interactions and suggests that the reduction of HDL-C in response to testosterone can occur without further metabolism of the androgen. The benefits/side effects of therapeutic intervention with antiandrogens could be studied in such a model. © 1990.