Can testosterone injections cause hyperlipidemia and hematochromatosis?

Testosterone Injections and Risk of Erythrocytosis and Lipid Effects

Testosterone injections can cause erythrocytosis (elevated hematocrit) but have minimal effects on lipid profiles at physiologic doses and are not associated with hemochromatosis. 1, 2

Erythrocytosis Risk

• Testosterone stimulates erythropoiesis, with injections carrying the highest risk of erythrocytosis compared to other administration routes 1
• Intramuscular testosterone injections cause erythrocytosis in up to 43.8% of patients, compared to only 15.4% with transdermal patches 2
• The risk increases with dosage - occurring in 2.8% with low-dose patches, 11.3% with 50 mg/day gel, and 17.9% with 100 mg/day gel 1
• Erythrocytosis is associated with supraphysiologic levels of bioavailable testosterone and estradiol 1

Clinical Significance of Erythrocytosis

• Elevated hematocrit increases blood viscosity, potentially aggravating vascular disease in coronary, cerebrovascular, or peripheral circulation 1
• Risk is particularly concerning in elderly patients and those with conditions already associated with increased hematocrit (e.g., COPD) 2
• FDA labeling specifically recommends monitoring hemoglobin and hematocrit levels to detect polycythemia in patients receiving long-term androgen administration 3

Effects on Lipid Profile

• Testosterone replacement therapy at physiologic doses has minimal to neutral effects on lipid profiles 1
• Multiple controlled studies show no change or only minimal reductions in HDL, often with a reduction in total cholesterol 1
• Only supraphysiologic doses (600 mg/week) significantly reduce HDL levels 1
• A meta-analysis of testosterone trials found only a small decrease in HDL cholesterol (WMD, -0.49 mg/dl) of unknown clinical significance 4

Hemochromatosis and Testosterone

• There is no evidence that testosterone therapy causes hemochromatosis 1
• Hemochromatosis is a genetic disorder of iron metabolism, not a direct consequence of testosterone therapy 5
• Some case reports suggest that patients with H63D heterozygosity in the HFE gene may be predisposed to developing erythrocytosis when receiving testosterone, particularly when combined with SGLT-2 inhibitors 6
• Testosterone suppresses hepcidin (an iron regulatory peptide), which may explain the mechanism behind testosterone-induced erythrocytosis, but this does not cause hemochromatosis 7

Monitoring Recommendations

• Regular monitoring of hemoglobin and hematocrit is essential for patients on testosterone therapy 3
• If erythrocytosis develops, appropriate measures include dosage reduction, withholding testosterone, therapeutic phlebotomy, or blood donation 1
• FDA labeling instructs patients to report symptoms including nausea, vomiting, changes in skin color, and ankle swelling 3
• Patients with risk factors for erythrocytosis should be monitored more closely 2

Special Considerations

• Combined use of testosterone and SGLT-2 inhibitors may increase risk of erythrocytosis in patients with type 2 diabetes 8, 6
• Elderly patients require particular vigilance due to higher risk of vascular complications from erythrocytosis 2
• Patients should be informed about the risk of erythrocytosis before starting testosterone therapy 2