Testosterone Undecanoate
A very long-acting testosterone ester used clinically as a long-interval depot injection (Nebido/Aveed) and as an oral preparation. Once cleaved it is bioidentical testosterone; the exceptionally long undecanoate ester allows dosing every 10-14 weeks by injection.
01 Overview
Testosterone undecanoate carries an eleven-carbon ester, the longest of the common testosterone esters. As the injectable depot Nebido (Europe) and Aveed (US), it is dosed at long intervals — a loading dose followed by injections every 10-14 weeks — making it a mainstay of clinical testosterone replacement.
An oral form also exists, absorbed via the intestinal lymphatics to partially bypass first-pass hepatic metabolism, so unlike 17-alpha-alkylated orals it is not meaningfully hepatotoxic. In all forms the liberated hormone is testosterone, so the pharmacodynamics are identical; the distinguishing feature is the very slow, stable release.
02 Mechanism
Esterases slowly cleave the undecanoate ester, releasing free testosterone over weeks. The hormone activates the androgen receptor, aromatises to estradiol, and suppresses gonadotropins by negative feedback.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Oral TRT | 160–240 mg/day | Oral | Andriol/Jatenzo taken with fatty meals, split doses; erratic absorption. |
| TRT depot | 1000 mg | IM | 1000 mg every 10-14 weeks after a loading interval. |
Ester comparison
| Ester | Half-life | Injection freq. | Testosterone by mass |
|---|
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Restored serum testosteroneLong depot gives stable eugonadal testosterone with infrequent injections; well documented in TRT trials. | Stable mid-normal levels | Clinical | |
| Increased lean massImprovement in fat-free mass and reduction in fat mass over months of therapy. | +2-5 kg | Clinical | |
| Improved libido, mood and bone densityCorrection of hypogonadism improves sexual function, mood and bone mineral density. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| HPTA suppressionSuppression of endogenous LH/FSH and spermatogenesis; the long depot means suppression persists for months after the last dose. | Severe | Universal | Clinical | |
| Pulmonary oil microembolism (POME)The large-volume oil depot carries a rare risk of oil microembolism and anaphylaxis, prompting an observation period after injection (Aveed REMS). | Severe | Rare | Clinical | |
| ErythrocytosisRaised hematocrit from androgen-stimulated erythropoiesis. | Moderate | Common | Clinical |