Methyltestosterone is a synthetic androgen developed in the early 20th century and introduced for medical use in the 1930s. It is one of the earliest orally active anabolic-androgenic steroids and has been used in the treatment of male hypogonadism, delayed puberty in males, and certain cases of breast cancer in women. Its history is marked by its ability to mimic the effects of natural testosterone, promoting development of male secondary sexual characteristics and supporting androgen replacement therapy. Over time, its clinical use has become more limited due to the development of safer and more selective androgen formulations, as well as concerns regarding hepatotoxicity and hormonal side effects.
BRAND NAMES
Android – commonly used for androgen replacement therapy
Metandren – an older branded formulation
Testred – another marketed oral formulation in some regions.
MECHANISM OF ACTION
Methyltestosterone is a synthetic androgen that exerts its effects by binding to intracellular androgen receptors in target tissues. After oral administration, it diffuses into cells and is converted into an active receptor–hormone complex that enters the nucleus and regulates gene transcription.
PHARMACOKINETICS:
Absorption:
Methyltestosterone is well absorbed after oral administration due to its chemical modification (17-α-alkylation), which allows it to survive first-pass hepatic metabolism. However, this modification also contributes to potential liver toxicity. Peak plasma concentrations are typically reached within 1–3 hours after oral intake. Bioavailability is variable but sufficient for systemic androgenic effects.
Distribution:
Methyltestosterone is widely distributed in body tissues and binds extensively to plasma proteins, including sex hormone-binding globulin (SHBG) and albumin. It readily enters target tissues such as muscle, bone, and reproductive organs where androgen receptors are expressed.
Metabolism:
It is extensively metabolized in the liver, primarily through reduction and conjugation pathways. Hepatic metabolism produces inactive metabolites, and because of its 17-α-alkylated structure, it undergoes slower degradation compared to natural testosterone.
Elimination:
The drug and its metabolites are excreted mainly via the urine, with a smaller fraction eliminated in feces. Elimination half-life is relatively short, but biological effects persist longer due to receptor binding and gene transcription activity.
PHARMACODYNAMICS:
Methyltestosterone acts as an androgen receptor agonist. After entering target cells, it binds to intracellular androgen receptors and the hormone-receptor complex translocates to the nucleus, where it regulates gene transcription. This leads to increased protein synthesis, promoting anabolic effects (muscle and bone growth) and androgenic effects (development of male secondary sexual characteristics) such as deepening of the voice, increased facial and body hair, and maturation of reproductive tissues. It also influences libido and overall endocrine balance.
ADMINISTRATION:
Methyltestosterone is administered orally in tablet form. It may be used alone or as part of combination hormone therapy. Due to its hepatotoxic potential, it is typically prescribed at the lowest effective dose for the shortest duration necessary.
DOSAGE AND STRENGTH:
Common adult dosing ranges from 10–50 mg per day, divided into multiple doses depending on indication (e.g., hypogonadism or delayed puberty). Dosage must be individualized based on patient response and tolerance, and long-term use requires careful monitoring of liver function and hormone levels.
DRUG INTERACTIONS:
Methyltestosterone may interact with anticoagulants (such as warfarin), increasing bleeding risk. It can also alter glucose metabolism, affecting insulin or antidiabetic drug requirements. Concurrent use with hepatotoxic drugs increases the risk of liver damage.
FOOD INTERACTIONS:
Food does not significantly affect absorption, but taking methyltestosterone with meals may reduce gastrointestinal discomfort. Alcohol should be avoided or limited due to increased risk of liver toxicity.
CONTRAINDICATIONS:
Methyltestosterone is contraindicated in patients with prostate or breast cancer (males), severe liver disease, and pregnancy. It should also be avoided in individuals with hypersensitivity to androgenic steroids.
SIDE EFFECTS:
Common side effects include acne, oily skin, fluid retention, increased aggression or mood changes, nausea, and changes in libido. In females, it may cause virilization such as voice deepening and hirsutism. Long-term use may lead to suppression of natural testosterone production and liver dysfunction.
OVER DOSAGE:
Overdose of Methyltestosterone is uncommon but may lead to exaggerated androgenic and hepatic effects rather than immediately life-threatening toxicity. Acute symptoms can include nausea, vomiting, abdominal discomfort, headache, dizziness, and mood changes such as irritability or aggression. In higher or prolonged excessive exposure, patients may develop signs of androgen excess, including acne, fluid retention, and changes in libido or behavior.
TOXICITY:
Toxicity of Methyltestosterone is mainly related to hepatotoxicity, including cholestatic jaundice and, in severe cases, liver tumors. Other toxic effects include excessive androgenic activity (virilization, infertility, testicular atrophy), lipid profile disturbances, and cardiovascular risk. Overdose is managed supportively, with discontinuation of the drug and monitoring of liver function and endocrine status.
