What is the effect of testosterone therapy on lipids?

From the Guidelines

Testosterone therapy within the physiologic range is not associated with worsening of the lipid profile, and significant changes in lipids are only seen at supraphysiologic doses. When considering the effects of testosterone therapy on lipids, it is essential to differentiate between physiologic and supraphysiologic doses, as the latter may lead to reductions in HDL cholesterol, as observed in a study where the highest dose of testosterone (600 mg per week) caused a significant reduction in HDL 1. However, at physiologic doses, testosterone therapy does not significantly alter total cholesterol, LDL, very-low-density lipoprotein, triglycerides, or C-reactive protein levels, as demonstrated in a study involving healthy men receiving transdermal testosterone, which showed no significant difference in serum levels of lipids and apolipoprotein during 36 months of treatment 1.

Key points to consider when evaluating the impact of testosterone therapy on lipids include:

• Transdermal administration of testosterone appears to have minimal effects on lipid profiles 1
• Intramuscular administration of testosterone also does not significantly affect HDL levels or the ratio of total cholesterol to HDL 1
• Lifestyle modifications, such as diet improvements, regular exercise, and weight management, should be implemented if adverse lipid changes occur
• Statin therapy may be considered if lipid abnormalities persist, with medications like atorvastatin or rosuvastatin being common choices

It is crucial to monitor lipid profiles in men on testosterone replacement therapy, with recommended monitoring at baseline, 3-6 months after starting treatment, and then annually. Common testosterone preparations include testosterone cypionate or enanthate injections, transdermal gels, or patches. The clinical significance of lipid changes from testosterone therapy remains uncertain, as testosterone therapy has not been conclusively linked to increased cardiovascular risk in most men and may even provide cardiovascular benefits through other mechanisms like improved insulin sensitivity and reduced body fat 1.

From the Research

Effect of Testosterone Therapy on Lipids

The effect of testosterone therapy on lipids is a complex topic with varying results from different studies.

• Testosterone administration has been shown to decrease the level of high-density lipoprotein cholesterol (HDL-C) 2, which is considered a beneficial effect for cardiovascular health.
• However, testosterone therapy has also been shown to decrease total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in hypogonadal and elderly men 3, which could have a beneficial effect on lipid metabolism.
• Exogenous testosterone administration has been associated with decreased HDL-C coupled with beneficial decreases in LDL-C and total cholesterol 4.
• The relationship between endogenous testosterone and lipids has also been studied, with low endogenous testosterone associated with high LDL-C and low HDL-C in both cross-sectional and prospective observational studies 4.
• The effect of testosterone on lipid profiles under statin therapy has also been examined, with results showing that testosterone levels are positively correlated with LDL-C levels, which are mildly lowered in proportion with LDL-C lowering under mild statin therapy 5.

Lipid Profile Changes

Changes in lipid profiles due to testosterone therapy have been observed in several studies.

• A decrease in HDL-C levels has been observed in some studies 2, while others have found no significant decrease in HDL-C levels or its subfractions 3.
• A decrease in total cholesterol and LDL-C levels has been observed in hypogonadal and elderly men 3.
• The ratio of HDL-C:LDL-C has been shown to decrease, while the TC:HDL-C ratio has been shown to increase in the testosterone group 2.

Clinical Implications

The clinical implications of the effect of testosterone therapy on lipids are still unclear.

• The overall impact of testosterone administration on cardiovascular disease (CVD) is still unclear, with mixed safety results from recent randomized controlled trials 4.
• There may be CVD risk reduction benefits, including an improved lipid profile, from testosterone administration in hypogonadal men 4.
• The effect of testosterone on CVD risk has not been definitively determined, and further studies are needed to fully understand the relationship between testosterone therapy and lipid metabolism 4.