Does IM Testosterone Increase Liver Enzymes?
No, intramuscular testosterone does not cause clinically significant liver enzyme elevations and routine monitoring with liver function tests is unnecessary for men receiving IM testosterone. 1
Key Evidence from Guidelines
The New England Journal of Medicine guidelines explicitly state that intramuscular injections and transdermal preparations of testosterone do not appear to be associated with hepatic dysfunction, making routine liver function test monitoring unnecessary for these formulations. 1 This stands in stark contrast to oral testosterone preparations (excluding testosterone undecanoate), which are strongly discouraged in the United States due to associated hepatotoxicity and risk of hepatic neoplasia. 1
Clinical Context and Nuances
When transient elevations may occur:
- The American Association for the Study of Liver Diseases acknowledges that testosterone replacement therapy may be associated with transient elevations in liver enzymes that are usually self-limited. 1 This is an important distinction—transient and self-limited elevations do not constitute hepatotoxicity requiring routine monitoring.
Supporting research evidence:
- A study of 88 men treated with intramuscular testosterone undecanoate for one year showed no significant increase in liver enzymes. 2
- In men with established cirrhosis and low testosterone, a 12-month randomized controlled trial of IM testosterone undecanoate demonstrated safety without increased adverse events, including no problematic liver enzyme elevations. 3
- Another study of 117 hypogonadal men treated with parenteral testosterone undecanoate actually showed significant decreases in ALT, AST, and inflammatory markers after one year. 4
Important Caveats
Route of administration matters critically:
- Oral testosterone (17-alpha-alkylated preparations) causes hepatotoxicity and should be avoided. 1
- IM and transdermal formulations have fundamentally different hepatic safety profiles. 1
Supraphysiologic or illicit use:
- A case report of a 27-year-old who self-medicated with high-dose IM and oral testosterone for one year developed cholestatic liver injury with total bilirubin of 11.4 mg/dL and elevated liver enzymes, which resolved with conservative management. 5 This represents abuse rather than therapeutic use.
Special populations:
- Testosterone can be safely used in men with chronic liver disease, including those with cirrhosis, with benefits including increased muscle mass and bone density. 1, 3
- Female-to-male transgender patients should be screened for liver abnormalities before initiating high-dose androgen therapy. 1
Bottom Line for Clinical Practice
Do not routinely monitor liver enzymes in patients receiving therapeutic IM testosterone. 1 Focus monitoring efforts on hematocrit (which commonly increases with IM formulations), prostate parameters, and cardiovascular risk factors instead. 1, 6