Methyltestosterone
An orally active testosterone derivative bearing a 17-alpha-methyl group that resists hepatic breakdown. It delivers testosterone-like androgenic effects by mouth, but the 17-alpha-alkylation makes it distinctly hepatotoxic — the key difference from injectable esters, which are not.
01 Overview
Methyltestosterone was one of the first orally active androgens, introduced in the late 1930s. The 17-alpha-methyl group blocks first-pass hepatic metabolism so the drug survives oral dosing, but that same modification makes it hepatotoxic, and it is a comparatively weak, harsh androgen with an unfavourable ratio of effects to liver strain.
Because of hepatotoxicity and poor lipid effects it has largely been abandoned for testosterone replacement in favour of transdermal and injectable testosterone. It retains niche use (for example in some combination products and historically for delayed puberty and certain breast cancers). Its downstream androgenic and estrogenic actions are testosterone-like, but the oral 17-AA route adds liver toxicity that injectable esters do not carry.
02 Mechanism
The 17-alpha-methyl group confers oral bioavailability by resisting hepatic 17-beta-oxidation. The compound acts as an androgen at the androgen receptor and aromatises (to 17-alpha-methylestradiol), while suppressing gonadotropins; hepatic processing of the alkylated steroid drives cholestatic and hepatocellular toxicity.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Therapeutic | 10–50 mg/day | Oral | Historical replacement dosing; largely superseded. |
| Common (non-clinical) | 25–50 mg/day | Oral | Liver strain rises steeply with dose and duration. |
Ester comparison
| Ester | Half-life | Injection freq. | Testosterone by mass |
|---|
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Oral androgenic effectProvides testosterone-like androgenic activity without injection, historically used for hypogonadism and delayed puberty. | Clinical | ||
| Increased libido and aggressionFast oral onset produces a subjective drive/aggression effect. | Observational | ||
| Modest lean mass and strength gainsWeaker and harsher milligram-for-milligram than injectable testosterone, with a poor effect-to-toxicity ratio. | Modest | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Adverse lipid changesOral 17-AA androgens sharply lower HDL and raise LDL, worsening cardiovascular risk more than injectable testosterone. | Moderate | Very common | Clinical | |
| Hepatotoxicity17-alpha-alkylation causes dose- and duration-dependent cholestatic liver injury, raised transaminases, and rarely peliosis hepatis or hepatic tumours. | Severe | Common with oral 17-AA use | Clinical | |
| HPTA suppressionSuppression of endogenous LH/FSH and spermatogenesis. | Severe | Universal | Clinical |