What is more hepatotoxic, injectable testosterone (testosterone) or oral methenolone (Primobolan)?

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Last updated: April 29, 2025View editorial policy

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From the Guidelines

Oral primobolan is more toxic to the liver than injectable testosterone due to its 17-alpha-alkylation and first-pass metabolism effects. This is because oral anabolic steroids, including primobolan (methenolone acetate), must pass through the liver during first-pass metabolism, placing additional stress on this organ 1. Injectable testosterone bypasses this first-pass effect since it enters the bloodstream directly. The chemical structure of oral primobolan includes a 17-alpha-alkylation, which is specifically designed to survive liver metabolism but consequently increases hepatotoxicity. Some key points to consider when evaluating the liver toxicity of these substances include:

  • The use of oral preparations of testosterone has been reported to lead to hepatotoxic effects and neoplasia, including benign and malignant tumors 1
  • Clinicians should not prescribe alkylated oral testosterone due to the associated liver toxicity, including abnormal liver function tests, cholestasis, and jaundice 1
  • Injectable testosterone esters (like testosterone cypionate, enanthate, or propionate) don't have the 17-alpha-alkylation modification and are therefore less stressful to the liver
  • Both substances can potentially cause liver damage, especially at high doses or with prolonged use, and other side effects include cardiovascular issues, hormonal imbalances, and potential suppression of natural testosterone production. It's essential to prioritize the patient's health and well-being by avoiding the use of oral primobolan and instead opting for injectable testosterone or other safer alternatives, under the guidance of a qualified medical professional.

From the Research

Liver Toxicity Comparison

  • The liver toxicity of injectable testosterone versus oral primobolan (methenolone acetate) is a complex topic that requires examination of various studies.
  • According to 2, methenolone acetate has a lower index of dissociation between anabolic and androgenic activity compared to other anabolic agents, which may indicate a lower potential for liver toxicity.
  • However, a study on the metabolism of methenolone acetate in humans found that it is metabolized into several compounds, including some that may be potentially toxic to the liver 3.
  • On the other hand, injectable testosterone has been shown to be generally safe and effective for combating loss of muscle and bone in older men, with a potentially better cardiovascular risk profile compared to oral or transdermal testosterone replacement therapy 4.
  • Additionally, a study on the pharmacokinetics and safety of subcutaneous testosterone therapy found that it results in comparable pharmacokinetics and mean serum testosterone levels to intramuscular administration, with potentially less discomfort and easier self-administration 5.
  • It is worth noting that the liver toxicity of both injectable testosterone and oral primobolan can be influenced by various factors, including dosage, duration of use, and individual patient characteristics.
  • Overall, while there is limited direct evidence comparing the liver toxicity of injectable testosterone and oral primobolan, the available data suggest that injectable testosterone may be a safer option, particularly when administered via subcutaneous injection 5, 4.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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