Does Testosterone Replacement Therapy (TRT) increase hypercalcemia and hypercholesterolemia?

From the Guidelines

Testosterone replacement therapy (TRT) generally does not significantly increase calcium levels but can have a minimal impact on cholesterol levels, with most studies showing no change or only a minimal reduction in HDL and total cholesterol levels 1.

Key Points

• TRT typically has minimal impact on serum calcium, as testosterone does not directly regulate calcium metabolism in the body.
• The effect of TRT on cholesterol levels is usually modest and should be monitored, especially in patients with pre-existing cardiovascular risk factors.
• Regular lipid panel testing is recommended before starting TRT and periodically during treatment, typically every 6-12 months.
• If significant adverse cholesterol changes occur, lifestyle modifications or lipid-lowering medications may be needed while continuing TRT.
• Patients with existing cardiovascular disease should discuss these potential effects with their healthcare provider before starting treatment, as the current evidence does not definitively demonstrate that testosterone therapy increases the risk of major adverse cardiovascular events (MACE) 1.

Considerations

• The impact of TRT on cholesterol profiles can vary between individuals, with some studies showing a decrease in HDL (good) cholesterol and a potential increase in LDL (bad) cholesterol.
• The influence of testosterone on liver enzyme activity related to cholesterol metabolism and lipoprotein production may contribute to these lipid changes.
• Clinicians should counsel patients that the current scientific literature does not definitively demonstrate that testosterone therapy increases the risk of MACE, and men on testosterone therapy should be advised to report any possible cardiovascular symptoms during routine follow-up visits 1.

From the FDA Drug Label

5.13 Lipids 5.14 Hypercalcemia

The FDA drug label mentions Lipids and Hypercalcemia as potential concerns, but it does not directly state that TRT increases calcium levels and cholesterol levels.

• Hypercalcemia is listed as a warning, implying a potential risk of elevated calcium levels.
• Lipids are also mentioned, suggesting a potential impact on cholesterol levels. However, without explicit statements on the effects of TRT on calcium and cholesterol levels, no conclusion can be drawn 2.

From the Research

Effects of TRT on Calcium Levels

• There is evidence to suggest that testosterone replacement therapy (TRT) can improve bone mineral density (BMD) in hypogonadal men, particularly at the lumbar spine 3.
• TRT has been shown to increase BMD by +3.7% (CI: 1.0--6.4%) compared to placebo, although the effects on bone resorption markers were inconsistent 3.
• However, the relationship between testosterone levels and osteoporosis development has been conflicting in human epidemiological studies, and no evidence supports the hypothesis that TRT can prevent the incidence of bone fracture 4.

Effects of TRT on Cholesterol Levels

• Testosterone administration has been associated with decreased high-density lipoprotein (HDL)-cholesterol, as well as beneficial decreases in low-density lipoprotein (LDL)-cholesterol and total cholesterol 3, 5.
• A significant reduction of HDL-cholesterol was found only in studies with higher mean testosterone values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003) 3.
• The overall impact of testosterone administration on cardiovascular disease (CVD) risk is still unclear, with mixed safety results from recent randomized controlled trials 5, 6.
• Low endogenous testosterone is associated with high LDL and low HDL in both cross-sectional and prospective observational studies, suggesting a potential CVD risk reduction benefit from testosterone administration in hypogonadal men 5.