Related Experiment Video
Updated: May 12, 2026

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
HDL cholesterol subfractions and the effect of testosterone replacement in hypogonadism
Insights
Hypogonadism is linked to poor cardiovascular health and unfavorable HDL composition. Testosterone replacement therapy did not improve these metabolic issues or HDL subfractions in a six-month study.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Metabolic Health
Background:
- Hypogonadism is associated with increased metabolic disorders and cardiovascular events.
- Serum high-density lipoprotein (HDL) composition is a critical cardiovascular risk predictor, yet its subfractions in hypogonadism remain understudied.
- Congenital hypogonadotropic hypogonadism (CHH) presents unique metabolic challenges.
Purpose of the Study:
- To investigate HDL subfractions in treatment-naïve young males with CHH.
- To evaluate the effects of two distinct testosterone replacement therapy (TRT) regimens on HDL subfractions.
- To assess the relationship between total testosterone levels and HDL subfractions.
Main Methods:
- A prospective study involving 70 young males with CHH and 70 age/BMI-matched healthy controls.
- Participants received either intramuscular testosterone esters (250 mg every 3 weeks) or daily transdermal testosterone (50 mg).
- Biochemical analyses included HDL subfractions (HDL2, HDL3), insulin resistance markers (HOMA-IR), and other metabolic parameters.
Main Results:
- CHH patients exhibited higher insulin, HOMA-IR, waist circumference (WC), triglycerides, and diastolic blood pressure compared to controls.
- While total HDL cholesterol was similar, hypogonadal patients had lower HDL2 and higher HDL3 levels.
- Total testosterone levels were independent predictors of HDL2 subfractions. Six months of TRT showed no significant improvement in metabolic issues or HDL composition, with no difference between treatment arms.
Conclusions:
- Hypogonadism is characterized by dysmetabolic features and unfavorable HDL composition (lower HDL2, higher HDL3).
- Testosterone replacement therapy over six months did not ameliorate these metabolic problems or improve HDL subfraction profiles.
- Further mechanistic studies are needed to elucidate the cardiovascular implications of altered HDL composition in hypogonadism.
Abstract:
Metabolic disorders and cardiovascular events are increased in hypogonadism. Serum HDL composition is a better cardiovascular predictor than the HDL counts. However, there is no information about the HDL subfractions in patients with hypogonadism. We designed a prospective study to investigate the HDL subfractions in treatment naïve subjects with hypogonadism and the effects of 2 different testosterone replacement regimens on the HDL subfractions. Seventy young male patients with congenital hypogonadotropic hypogonadism (CHH) and 70 age and BMI-matched healthy males were enrolled in the present study. The patients were assigned to receive intramuscular injections of testosterone esters 250 mg every 3 weeks and transdermal testosterone applications 50 mg daily. Biochemical investigations including HDL subfractions and insulin resistance were done. Patients with CHH had higher levels of insulin, HOMA-IR, WC, triglyceride, and diastolic blood pressure. Although, the HDL cholesterol concentrations were similar in both groups, hypogonadal patients had lower HDL2 and higher HDL3 levels. The total testosterone levels were independent determinants of the HDL2 subfractions. During the follow-up, a significant increase in the BMI and WC values and a significant decrease in the levels of total cholesterol, HDL cholesterol, and HDL3 were observed. No difference was present between the 2 treatment arms. These results show that patients with hypogonadism have unfavorable HDL compositions in addition to the other dysmetabolic features. However, testosterone replacement for about six months neither improves the metabolic problems nor the HDL composition. Mechanistic studies are warranted to better understand the cardiovascular effects of unfavorable HDL compositions in hypogonadism.
Related Concept Videos
Cholesterol: Significance and Regulation
Considering cholesterol and...
Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Testosterone: Functions and Regulation
Atherosclerosis III: Management
Lipids: Dietary Sources and Requirements
