Suppression of Plasma Testosterone Leads to an Increase in Serum Total and High Density Lipoprotein Cholesterol and Apoproteins A-I and B*

Abstract

Men have lower high density lipoprotein (HDL)and higher low density lipoprotein (LDL) levels than women.To dynamically evaluate the role of endogenous testosterone onthe lipoprotein profile, eight normal men received a long-actinggonad otropin releasing hormone analog (LHRH_A) for 10 weeksby SC injection. Plasma testosterone levels were acutely loweredbelow 1 ng/ml after 4 weeks of LHRH_A treatment and remaineddepressed at this level for the duration of administration of theanalog. There were prompt increases in total cholesterol [baselineus. peak (milligrams per dl) mean ± SEM, 177 ± 18 vs. 208± 22; P < 0.005], apoprotein B (apo B; 69 ± 12 vs. 97 ± 13; P vs. 33 ± 2; P < 0.005), and apoA-I (80 ± 7 vs. 112 ± 5; P < 0.005), but not in apo A-II (40 ± 3 vs. 40 ± 4; P = NS) levels. The peaks occurred after 10 weeks oftreatment and were followed by a fall in these values afterdiscontinuing LHRH_A. These changes were largely prevented ina second study (six men) in which LHRHA was administeredtogether with im testosterone enanthate, which was given every 2 weeks. These results show that suppression of endogenoustestosterone leads to increases in HDL and LDL, demonstratingthat testosterone has an important effect on lipoprotein metabolismand plays a key role in defining the lipoprotein profile inmen.