Methyltestosterone (Android, Testred) - Oral Androgen — Anabolic Steroids
The oldest oral androgen (synthesized 1935), a C-17α alkylated testosterone derivative FDA-approved for male hypogonadism with significant hepatotoxicity concerns including peliosis hepatis.
Overview
Methyltestosterone is the 17α-methylated derivative of testosterone, first synthesized in 1935 and among the earliest oral androgens available. FDA-approved under brand names Android and Testred for the treatment of male hypogonadism, delayed puberty, and (historically) inoperable breast cancer in women. The 17α-alkyl group confers oral bioavailability by resisting first-pass hepatic metabolism but simultaneously creates significant hepatotoxic potential, including cholestatic jaundice, peliosis hepatis, and hepatocellular carcinoma with chronic use. Methyltestosterone is also available in combination with esterified estrogens (Estratest) for vasomotor symptoms in postmenopausal women, though this use has become controversial. It undergoes both aromatization (to 17α-methylestradiol) and 5α-reduction, contributing to estrogenic and androgenic side effects respectively. Largely superseded by safer testosterone preparations (injections, transdermals, pellets) in modern clinical practice. PMID: 2660329, 3211809, 7483849.
Indications
- Male hypogonadism (primary and hypogonadotropic) - FDA-approved
- Delayed puberty in males - FDA-approved for short-term use
- Postmenopausal vasomotor symptoms (in combination with esterified estrogens; Estratest)
- Historical: inoperable metastatic breast cancer in women (1-5 years postmenopause)
- Bodybuilding and performance enhancement (off-label, largely replaced by safer compounds)
Mechanism of Action
The C-17α methyl group protects the steroid from first-pass hepatic degradation, allowing oral bioavailability of ~44%, but creating hepatotoxic alkylated metabolites
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Methyltestosterone | 10 mg | Once daily | Starting dose for hypogonadism; assess response before increasing |
| Methyltestosterone | 25 mg | Once daily | Standard replacement dose for male hypogonadism |
| Methyltestosterone | 50 mg | Once daily | Maximum recommended dose; significantly increased hepatotoxicity risk |
| Methyltestosterone | 5-25 mg | Once daily (buccal absorption) | Buccal administration may improve bioavailability and reduce first-pass hepatic exposure |
| Estratest (esterified estrogens/methyltestosterone) | 1.25mg/2.5mg | Once daily | Postmenopausal vasomotor symptoms; lowest effective dose for shortest duration |
Evidence Grade
GRADE B
Safety & Contraindications
- Significant hepatotoxicity due to C-17α alkylation: cholestatic jaundice, peliosis hepatis (blood-filled hepatic cysts), and hepatocellular carcinoma reported with chronic use
- Adverse lipid effects: marked HDL suppression (up to 50%) and LDL elevation; substantially worse than injectable testosterone
- Virilization in females: deepening voice, hirsutism, clitoral enlargement, menstrual irregularities (often irreversible)
- Aromatizes to 17α-methylestradiol: gynecomastia, water retention, and estrogenic side effects possible
- FDA black box warning: peliosis hepatis, liver cell tumors, and blood lipid changes; periodic liver function monitoring required
- Contraindicated in pregnancy (Category X), prostate cancer, breast cancer in males, and severe hepatic dysfunction