Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I containing lipoproteins

Clin Endocrinol (Oxf). 1998 Feb;48(2):187-94.


Objectives: Gonadal steroids are important regulators of lipoprotein metabolism. The aims of this study were to determine the effects of a minimum effective dose of testosterone replacement on high density lipoprotein (HDL) subfractions and apolipoprotein (apo) A-I containing particles (lipoprotein (Lp)A-I) and LpA-I:A-II) in hypogonadal men with primary testicular failure and to investigate the underlying mechanisms of these changes.

Measurements: Eleven Chinese hypogonadal men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly intervals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of treatment. Plasma cholesteryl ester transfer protein (CETP) activity and lipolytic enzymes activities in post-heparin plasma were measured to determine the mechanisms underlying testosterone-induced changes in HDL.

Results: The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No changes were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after 12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in plasma CETP and lipoprotein lipase activities after testosterone replacement but there was a transient increase in hepatic lipase (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase in HL activity (r = 0.62, P < 0.05).

Conclusions: Testosterone replacement in the form of parenteral testosterone ester given 4-weekly, although unphysiological, was not associated with unfavourable changes in lipid profiles. The reduction in HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti-atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.

MeSH terms

  • Adult
  • Apolipoprotein A-I / metabolism*
  • Carrier Proteins / blood
  • Cholesterol / blood
  • Cholesterol Ester Transfer Proteins
  • Estradiol / blood
  • Follicle Stimulating Hormone / blood
  • Glycoproteins*
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / drug therapy*
  • Lipase / metabolism
  • Lipoproteins, HDL / metabolism*
  • Liver / enzymology
  • Luteinizing Hormone / blood
  • Male
  • Testosterone / blood
  • Testosterone / therapeutic use*
  • Triglycerides / blood


  • Apolipoprotein A-I
  • CETP protein, human
  • Carrier Proteins
  • Cholesterol Ester Transfer Proteins
  • Glycoproteins
  • Lipoproteins, HDL
  • Triglycerides
  • Testosterone
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Cholesterol
  • Lipase