Can Low Testosterone Cause High Cholesterol?
Yes, low testosterone levels are directly associated with an unfavorable lipid profile, including elevated total cholesterol and triglycerides, though the relationship with LDL cholesterol is more complex and may follow a U-shaped curve.
The Direct Association Between Low Testosterone and Lipid Abnormalities
Low endogenous testosterone is independently associated with dyslipidemia through several mechanisms:
- Triglycerides are most strongly affected: Men with testosterone levels below the 50th percentile demonstrate a linear increase in serum triglycerides throughout the day, while men with higher testosterone levels maintain stable triglyceride levels 1
- Total cholesterol elevation: Low testosterone concentrations prospectively predict higher total cholesterol levels, with men in the lowest testosterone quartile showing 0.20-0.23 mmol/L higher total cholesterol compared to those in the highest quartile 2
- HDL cholesterol reduction: Low testosterone is independently associated with lower HDL cholesterol levels, contributing to an atherogenic lipid profile 3
The Complex LDL Relationship
The association between testosterone and LDL cholesterol follows a U-shaped curve rather than a simple linear relationship:
- Men with both very low testosterone (<3.5 ng/mL) and very high LDL (>90th percentile) have 1.3-1.4 times higher odds of testosterone deficiency compared to men with mid-range LDL levels 4
- This suggests that both extremely low and extremely high LDL concentrations may be associated with low testosterone, though the mechanism remains unclear 4
- Most studies show LDL remains unchanged or decreases with testosterone replacement, indicating the relationship is not straightforward 5
Clinical Significance and Risk Stratification
Men with unfavorable lipid profiles (HDL <0.90 mmol/L and triglycerides >1.8 mmol/L) have significantly lower testosterone levels even after adjusting for age and BMI 1:
- Low testosterone predicts incident dyslipidemia with a relative risk of 1.28 for men in the lowest testosterone quartile 2
- This effect is particularly pronounced in younger men (ages 20-39), with a relative risk of 1.51 for developing dyslipidemia 2
- The association persists after controlling for obesity, diabetes, cardiovascular disease, smoking, and alcohol consumption 3
Mechanism of Action
Testosterone influences lipid metabolism through multiple pathways:
- Impaired triglyceride metabolism: Low testosterone appears to disrupt normal triglyceride clearance throughout the day, leading to sustained elevation 1
- Direct metabolic effects: Testosterone correlates inversely with triglycerides (r=-0.30) and directly with HDL cholesterol (r=0.24) in multivariate analyses 3
- Body composition mediation: While obesity contributes to both low testosterone and dyslipidemia, testosterone remains an independent predictor even after BMI adjustment 3, 2
Therapeutic Implications
When testosterone replacement is initiated at physiologic doses in hypogonadal men, lipid profiles typically improve rather than worsen:
- Total cholesterol decreases by 23-49 mg/dL after 6-12 months of testosterone replacement 6
- LDL cholesterol decreases by 13-38 mg/dL with physiologic testosterone replacement 6
- HDL cholesterol remains stable or shows minimal changes at physiologic replacement doses 5, 6
- Triglycerides show neutral to potentially beneficial effects with physiologic testosterone replacement 5
Critical Caveats
Route and dose matter significantly:
- Supraphysiologic doses (particularly oral nonaromatizable androgens) adversely affect lipids and should never be used 5
- Target testosterone levels should remain in the middle tertile of normal range (450-600 ng/dL) to minimize any potential HDL suppression 5
- Transdermal testosterone demonstrates the most neutral lipid effects in long-term studies 5
- Never prescribe 17-alpha-alkylated androgens (methyltestosterone) due to unfavorable lipid effects and hepatotoxicity 5