Testosterone undecanoate is testosterone with a long, 11-carbon fatty-acid ester (undecanoic acid) attached. Dissolved in castor oil and injected deep into the buttock muscle, it forms a depot that releases testosterone over about 10–14 weeks, so it is given four or five times a year. It is sold as Aveed in the US and as Nebido in the UK and Europe.
The long interval comes with a specific risk. Small droplets of the oil can reach the lungs during or just after an injection, an event called pulmonary oil microembolism (POME), and severe allergic reactions (anaphylaxis) have also been reported. In the US this is a boxed warning. Aveed is given only in certified clinics, and patients must be observed for 30 minutes after each shot.
The same ester is also made as an oral capsule, which behaves very differently. That form has its own page: oral testosterone undecanoate. This page summarizes what the FDA and UK labels, clinical trials and regulators report about the injection. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Androgen; anabolic-androgenic steroid (testosterone ester) |
| Brands / approval | Aveed (Endo), FDA approval March 5, 2014 (NDA 022219); Nebido (Grünenthal in the UK), UK authorization October 2004 |
| Route | Deep intramuscular injection into the gluteal muscle |
| Strengths | Aveed 750 mg/3 mL; Nebido 1000 mg/4 mL (both 250 mg/mL in castor oil and benzyl benzoate) |
| Labeled dose | Aveed: 750 mg at start, at 4 weeks, then every 10 weeks. Nebido: 1000 mg every 10–14 weeks |
| Depot half-life | 33.9 days in castor oil in a phase I study; the UK label gives a release half-life of 90 ± 40 days |
| Testosterone content | About 63% of the ester’s weight (1000 mg ≈ 632 mg testosterone) |
| Boxed warning (US) | Pulmonary oil microembolism and anaphylaxis; restricted REMS program |
| US schedule | Schedule III controlled substance |
| WADA status | Prohibited at all times (S1.1 anabolic androgenic steroids) |
What it is
The FDA label gives the chemical name as 17β-undecanoyloxy-4-androsten-3-one, formula C₃₀H₄₈O₃, molecular weight 456.7 (FDA label). The UK label states that each 1000 mg of the ester corresponds to 631.5 mg of testosterone (Nebido SmPC). By the same ratio, a 750 mg Aveed dose holds about 474 mg of testosterone.
The ester has no hormonal activity itself. Esterases in tissue and blood cut it off and release ordinary testosterone and undecanoic acid, which is broken down like other fatty acids. The very long, fat-soluble side chain is what makes the depot release so slowly.
The two marketed products use the same ester and concentration but different volumes:
| Feature | Aveed (US) | Nebido (UK / EU) |
|---|---|---|
| Dose per injection | 750 mg in 3 mL | 1000 mg in 4 mL |
| Oil carrier | Refined castor oil, 885 mg per vial | Refined castor oil |
| Solubilizer | Benzyl benzoate, 1500 mg per vial | Benzyl benzoate, 2000 mg per vial |
| Injection speed (label) | Slowly, over 60–90 seconds | Very slowly, over 2 minutes |
| Observation after injection | 30 minutes in a certified setting | Observe during and immediately after |
Early human studies in Münster, Germany, tested 1000 mg in two different oils. The castor-oil version lasted longer and needed a smaller injection volume, and the authors named it the stronger candidate for further development (Behre et al., Eur J Endocrinol 1999). Both marketed products use castor oil. A tea-seed-oil version was used in a large Chinese contraceptive trial.
Pharmacokinetics
The ester’s long chain slows its release from the oil, so blood testosterone rises and falls far more gradually than with testosterone cypionate or testosterone enanthate, which in the US are typically injected every 2–3 weeks (Wang et al., J Androl 2010).
Half-life
In the phase I studies, the depot half-life of 1000 mg was 33.9 ± 4.9 days in castor oil (14 hypogonadal men) and 20.9 ± 6.0 days in tea seed oil (7 men) (Behre et al., Eur J Endocrinol 1999). The UK label describes the release rate with a half-life of 90 ± 40 days. The FDA label does not give a half-life. Published figures therefore vary with the oil and the method used, but all of them are measured in weeks, not days.
Levels after injection
| Measure | Value | Source |
|---|---|---|
| Time to peak after 750 mg | Median 7 days (range 4–42) | FDA label |
| Unchanged ester in blood | Peak 90.9 ng/dL on day 4; nearly undetectable by day 42 | FDA label |
| Peak after first 1000 mg | 38 nmol/L (≈ 1,100 ng/dL) at day 7 | UK label |
| Steady state, 1000 mg | Reached between the 3rd and 5th injection | UK label |
| Steady-state peak and trough, 1000 mg | About 37 and 16 nmol/L (≈ 1,100 and 500 ng/dL) | UK label |
| Steady-state average, 750 mg | 495 ng/dL (peak 891, trough 324) | FDA label, n = 117 |
| DHT : testosterone ratio, 750 mg | 0.05–0.07 | FDA label |
Body weight matters. In the Aveed phase 3 study, men weighing 100 kg or more averaged 426 ng/dL, versus 568 ng/dL in men weighing 65–100 kg (FDA label).
Comparison with testosterone enanthate
A German trial randomized 40 hypogonadal men to 250 mg testosterone enanthate every 3 weeks or 1000 mg undecanoate every 6 weeks (loading), then after a 9-week gap (Schubert et al., JCEM 2004):
| Group | Mean trough testosterone before the next injection |
|---|---|
| Enanthate 250 mg every 3 weeks | Always under 10 nmol/L (≈ 290 ng/dL) |
| Undecanoate, after two 6-week intervals | 14.1 nmol/L (≈ 405 ng/dL) |
| Undecanoate, after the 9-week interval | 16.3 nmol/L (≈ 470 ng/dL) |
In the follow-up phase, 1000 mg every 12 weeks kept mean troughs at about 15–16.5 nmol/L for roughly 2.5 years. The authors noted this took four injections a year instead of 17 or more of enanthate.
Approved medical use
Both labels approve testosterone undecanoate injection only as replacement therapy in men with confirmed testosterone deficiency. The FDA label covers:
- primary hypogonadism (testicular failure);
- hypogonadotropic hypogonadism (pituitary or hypothalamic failure).
Diagnosis requires low morning testosterone on at least two separate days. The FDA label adds that Aveed should be used only when the benefit outweighs the risks of POME and anaphylaxis. Safety and efficacy have not been established for “age-related hypogonadism” or for males under 18.
| Item | Aveed (FDA label) | Nebido (UK label) |
|---|---|---|
| Starting doses | 750 mg, then 750 mg at 4 weeks | 1000 mg; second injection may be brought forward to 6 weeks |
| Maintenance | 750 mg every 10 weeks | 1000 mg every 10–14 weeks |
| Dose adjustment | “Dosage titration is not necessary” | Adjust interval by trough level, aiming for the lower third of the normal range |
| After the injection | 30-minute observation in a REMS-certified setting | Observation during and immediately after |
The UK label also states that androgens are not suitable for building muscle in healthy people or increasing physical performance (Nebido SmPC).
What the research shows
Keeping testosterone in the normal range
The US approval rests on an 84-week, single-arm, open-label phase 3 trial in 130 hypogonadal men given 750 mg at weeks 0 and 4 and then every 10 weeks (Wang et al., J Androl 2010). After the third injection, 117 men were evaluated (FDA label):
| Outcome | Result |
|---|---|
| Average testosterone in the normal range (300–1000 ng/dL) | 94% |
| Average below 300 ng/dL | 5.1% |
| Average above 1000 ng/dL | 0.9% |
| Peak above 1500 ng/dL | 7.7% |
| Peak above 1800 ng/dL | None |
The trial had no placebo or comparator group. It shows that the dosing schedule holds levels in range, not how symptoms compare with other treatments.
Symptoms in men with metabolic syndrome
A double-blind, placebo-controlled trial randomized 184 hypogonadal men with metabolic syndrome (mean BMI 35.5) to 1000 mg undecanoate or placebo at weeks 0, 6 and 18 (Giltay et al., J Sex Med 2010). At 30 weeks, compared with placebo:
| Scale | Difference vs placebo (95% CI) |
|---|---|
| Beck Depression Inventory (lower is better) | −2.5 points (−0.9 to −4.1) |
| Aging Males’ Symptoms scale (lower is better) | −7.4 points (−4.3 to −10.5) |
| IIEF-5 erectile function score (higher is better) | +3.1 points (1.8 to 4.4) |
The effects were largest in men with the lowest starting testosterone.
Type 2 diabetes prevention (T4DM)
T4DM is the largest randomized trial of injectable testosterone undecanoate. It enrolled 1,007 Australian men aged 50–74 with a large waist, testosterone of 14.0 nmol/L or lower (without pathological hypogonadism), and impaired glucose tolerance or newly diagnosed type 2 diabetes. All joined a lifestyle program. They received 1000 mg undecanoate or placebo at baseline, at 6 weeks, then every 3 months for 2 years (Wittert et al., Lancet Diabetes Endocrinol 2021):
| Outcome at 2 years | Placebo | Testosterone undecanoate |
|---|---|---|
| Type 2 diabetes on glucose tolerance test | 21% (87 of 413) | 12% (55 of 443) |
| Relative risk | — | 0.59 (95% CI 0.43–0.80) |
| Change in 2-h glucose | −0.95 mmol/L | −1.70 mmol/L |
| Hematocrit over 54% (safety trigger) | 1% (6 of 484) | 22% (106 of 491) |
| Prespecified serious adverse events | 7.4% | 10.9% |
The authors concluded that rises in hematocrit (the share of blood made up of red cells) “might be treatment limiting.” In a substudy, testosterone raised cortical bone density at the distal tibia (shin bone) by 3.1% (95% CI 1.2–5.0) over 2 years versus placebo. It also raised areal bone density at the spine and hip (Ng Tang Fui et al., JCEM 2021). The authors noted that effects on fracture risk and long-term cardiovascular safety still need study.
Male contraception
Because a steady testosterone level suppresses the pituitary signals that drive sperm production, the injection has been tested as a male contraceptive:
- Undecanoate alone. In a phase III trial, 1,045 healthy Chinese men received 500 mg of a tea-seed-oil formulation every month (Gu et al., JCEM 2009). 4.8% did not reach the target sperm suppression within 6 months. Among men who did, there were 9 pregnancies in 1,554 person-years, a cumulative failure rate of 1.1 per 100 men. Sperm counts returned to the fertile range in all but two men.
- With a progestin. A 10-center study gave 320 men 1000 mg undecanoate plus 200 mg norethisterone enanthate every 8 weeks (Behre et al., JCEM 2016). 95.9 per 100 continuing users suppressed to 1 million sperm/mL or fewer within 24 weeks, and the pregnancy rate was 1.57 per 100 continuing users. Injections were stopped early on the advice of an external safety committee, and mild to moderate mood disorders were relatively common.
Both labels approve the injection only for hypogonadism, not for contraception.
Side effects and risks
Boxed warning: oil microembolism and anaphylaxis
POME symptoms listed on the FDA label include urge to cough, shortness of breath, throat tightening, chest pain, dizziness and fainting. Most episodes lasted a few minutes, but some lasted hours and needed emergency care. Both POME and anaphylaxis can occur after any injection, including the first. Because of this, the FDA requires the following (FDA label):
- prescribers and healthcare settings must be certified in the Aveed REMS program;
- the setting must have equipment and trained staff to manage these reactions;
- every patient must be observed for 30 minutes after each injection.
How often it happens:
| Data source | Frequency reported |
|---|---|
| 18 clinical trials, 3,556 patients (FDA label) | 9 POME events in 8 patients; 2 anaphylaxis events |
| US post-marketing, 2014–2018, 90,092 doses (Pastuszak et al., Sex Med 2020) | 28 POME reports; under 0.1% per injection |
| UK label, clinical trials | Rare: 1 in 10,000 to 1 in 1,000 injections |
| Literature review, 29 studies, 7,978 patients (Adam et al., Int J Impot Res 2023) | 88 POME or cough cases in 8 studies; one post-market review: 223 per 3,107,652 injections |
In the post-marketing analysis, most events resolved within 30 minutes and more than 60% needed no treatment. Injection technique or dosing problems were identified in 3 of the 4 cases that required an emergency room visit.
Common side effects
In the 84-week Aveed study (n = 153), the most common adverse reactions were (FDA label):
| Reaction | Rate |
|---|---|
| Acne | 5.2% |
| Injection site pain | 4.6% |
| PSA above 4 ng/mL | 4.6% |
| Estradiol increased | 2.6% |
| Fatigue, irritability, insomnia, mood swings, hemoglobin increased | 2% each |
Overall, 4.6% stopped treatment because of adverse reactions, including raised hematocrit, raised PSA, prostate cancer and deep vein thrombosis.
Red blood cells
Testosterone stimulates red cell production. In T4DM, 22% of men on undecanoate crossed the hematocrit safety threshold of 54%, compared with 1% on placebo. The FDA label advises checking hematocrit before treatment, at 3–6 months and then yearly, and stopping until it falls if it becomes elevated. The UK label notes that combining testosterone with SGLT2 inhibitors (a class of diabetes drugs) has been linked to a higher risk of erythrocytosis (too many red cells).
Prostate
In the Aveed study, average PSA (prostate-specific antigen) rose from 1.0 to 1.5 ng/mL. 10.9% of men starting below 4 ng/mL went above it. Both labels contraindicate use in men with prostate cancer and advise prostate monitoring.
Blood pressure and the heart
In a 16-week ambulatory monitoring study (n = 139), Aveed raised average 24-hour blood pressure by 3.1/2.0 mm Hg (FDA label). The label says it is not recommended in uncontrolled hypertension. The label’s cardiovascular outcome data come from the TRAVERSE trial, which used testosterone gel rather than undecanoate injection; heart attack, stroke and cardiovascular death were similar to placebo (7.0% vs 7.3%). Venous blood clots have been reported with testosterone products.
Fertility and recovery after stopping
Exogenous testosterone shuts down the pituitary hormones LH and FSH, which reduces sperm production. The FDA label warns that the effect on fertility may be irreversible in some cases. After T4DM ended, 303 men were followed for another year (Handelsman et al., Eur J Endocrinol 2022). In men who had received undecanoate, LH and FSH started fully suppressed and recovered only slowly. The authors concluded that full recovery is slow and may take longer than 12 months after the last injection.
Interactions
- Diabetes medicines: testosterone can lower blood glucose, so insulin or other drug doses may need reducing.
- Warfarin: androgens can increase the anticoagulant effect, so INR should be checked more often.
- Corticosteroids: combined use can increase fluid retention.
Who should not use it
The labels list these contraindications:
- breast cancer or known or suspected prostate cancer in men;
- pregnancy (it can virilize a female fetus) and use in women generally;
- allergy to testosterone undecanoate, castor oil or benzyl benzoate;
- past or present liver tumors (UK label).
Monitoring
| What | When |
|---|---|
| Testosterone | Before treatment; UK label advises measuring at the end of an injection interval |
| Hematocrit and hemoglobin | Baseline, 3–6 months, then yearly (FDA label) |
| PSA and prostate exam | Before and during treatment; at least yearly (UK label) |
| Blood pressure | Periodically, especially in men with hypertension |
| Lipids and liver tests | Periodically |
Legal status
In the US, Aveed is labeled CIII: testosterone, including its esters, is a Schedule III controlled substance (21 CFR 1308.13). Testosterone and its esters are prohibited at all times in sport under section S1.1 of the WADA 2026 Prohibited List. The UK label warns that athletes treated for hypogonadism may test positive.
Key takeaways
- Four or five injections a year. One 750–1000 mg dose lasts about 10–14 weeks, because the long ester leaves the castor-oil depot slowly.
- Steadier levels than older esters. In the US phase 3 trial, 94% of men averaged within 300–1000 ng/dL, and no one peaked above 1800 ng/dL.
- A unique injection risk. Oil microembolism and anaphylaxis are rare, under 0.1% of injections in US post-marketing data, but they drive the US boxed warning, REMS and 30-minute observation.
- Hematocrit is the main lab to watch. In T4DM, 22% of men on undecanoate crossed 54% versus 1% on placebo.
- Slow to wear off. After 2 years of treatment, full recovery of LH and FSH may take more than a year after the last injection.
- Oral form is a different drug experience. The capsule version is covered on its own page: oral testosterone undecanoate.
Sources
- Endo USA. Aveed (testosterone undecanoate) injection, prescribing information, revised July 2025. DailyMed; Drugs@FDA, NDA 022219.
- Grünenthal Ltd. Nebido 1000 mg/4 ml solution for injection, Summary of Product Characteristics, revised December 2025. emc.
- Behre HM, Abshagen K, Oettel M, Hübler D, Nieschlag E. Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. Eur J Endocrinol. 1999;140(5):414–419. PubMed.
- Schubert M, Minnemann T, Hübler D, et al. Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism. J Clin Endocrinol Metab. 2004;89(11):5429–5434. PubMed.
- Wang C, Harnett M, Dobs AS, Swerdloff RS. Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial. J Androl. 2010;31(5):457–465. PubMed.
- Giltay EJ, Tishova YA, Mskhalaya GJ, et al. Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome. J Sex Med. 2010;7(7):2572–2582. PubMed.
- Wittert G, Bracken K, Robledo KP, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9(1):32–45. PubMed.
- Ng Tang Fui M, Hoermann R, Bracken K, et al. Effect of testosterone treatment on bone microarchitecture and bone mineral density in men: a 2-year RCT. J Clin Endocrinol Metab. 2021;106(8):e3143–e3158. PubMed.
- Gu Y, Liang X, Wu W, et al. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J Clin Endocrinol Metab. 2009;94(6):1910–1915. PubMed.
- Behre HM, Zitzmann M, Anderson RA, et al. Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab. 2016;101(12):4779–4788. PubMed.
- Pastuszak AW, Hu Y, Freid JD. Occurrence of pulmonary oil microembolism after testosterone undecanoate injection: a postmarketing safety analysis. Sex Med. 2020;8(2):237–242. PubMed.
- Adam JA, Pastuszak AW, Christensen MB, et al. Occurrence of pulmonary oil microembolism (POME) with intramuscular testosterone undecanoate injection: literature review. Int J Impot Res. 2023;35(5):439–446. PubMed.
- Handelsman DJ, Desai R, Conway AJ, et al. Recovery of male reproductive endocrine function after ceasing prolonged testosterone undecanoate injections. Eur J Endocrinol. 2022;186(3):307–318. PubMed.
- US Code of Federal Regulations. 21 CFR 1308.13, Schedule III. eCFR.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA.