Testosterone enanthate is testosterone with a seven-carbon heptanoate (“enanthate”) ester attached. The ester makes the hormone more fat-soluble, so it dissolves in an oil vehicle and releases slowly from the injection site. It is one of the oldest testosterone drugs in the US, first approved in 1953 as Delatestryl. It is still sold as a generic intramuscular (IM) injection and, since 2018, as Xyosted, a weekly subcutaneous autoinjector.
Many of the landmark trials on how testosterone affects muscle, red blood cells and sperm production used testosterone enanthate. As the FDA labels note, testosterone is also misused by athletes and bodybuilders, often alongside other anabolic-androgenic steroids (AAS).
This page summarizes what the FDA labels, clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Androgen; anabolic-androgenic steroid (testosterone ester) |
| Brands / approval | Delatestryl (NDA 009165, approved 1953, now discontinued); generic vials; Xyosted autoinjector (NDA 209863, approved 2018) |
| Route | Intramuscular (generic vials); subcutaneous in the abdomen (Xyosted) |
| Strengths | 200 mg/mL in sesame oil (generic); 50, 75 and 100 mg per 0.5 mL (Xyosted) |
| Labeled dose | IM: 50–400 mg every 2–4 weeks; Xyosted: 75 mg weekly, adjusted to 50 or 100 mg |
| Half-life | ≈4.5 days (pharmacokinetic review); the US labels do not state one for the ester |
| Testosterone content | ≈72% of the ester’s weight (200 mg ester ≈ 144 mg testosterone) |
| US schedule | Controlled substance, Schedule III |
| WADA status | Prohibited at all times (S1.1 anabolic androgenic steroids) |
What it is
Testosterone enanthate is the 17β-heptanoate ester of testosterone: formula C₂₆H₄₀O₃, molecular weight 400.6 g/mol (PubChem; Xyosted label). Testosterone itself weighs 288.4 g/mol (PubChem). The ester therefore accounts for about 28% of the weight, so a 200 mg dose delivers about 144 mg of testosterone.
The ester has no hormonal action of its own. As the generic label puts it, esterifying the 17β-hydroxy group lengthens the duration of action, and hydrolysis back to free testosterone occurs in the body (generic label). The released testosterone then acts like the body’s own hormone. It binds the androgen receptor directly and is also converted to:
- dihydrotestosterone (DHT), a more potent androgen;
- estradiol, the main estrogen.
The two current US products differ mainly in delivery:
| Feature | Generic IM vial | Xyosted autoinjector |
|---|---|---|
| Concentration | 200 mg/mL | 50, 75 or 100 mg per 0.5 mL |
| Vehicle | Sesame oil | Sesame oil |
| Preservative | Chlorobutanol 5 mg/mL | None (single-dose) |
| Injection site | Deep in the gluteal muscle | Abdominal skin (subcutaneous); IM use to be avoided |
| Labeled schedule | 50–400 mg every 2–4 weeks | 50–100 mg once weekly |
| Approved uses | Male hypogonadism, delayed puberty in boys, metastatic breast cancer in women | Male hypogonadism in adults only |
Testosterone cypionate is a closely related ester. The hematocrit meta-analysis cited below pools the two together.
Pharmacokinetics
Once testosterone is freed from the ester, it is cleared quickly. The generic label gives a half-life of 10–100 minutes for testosterone itself, with about 90% of a dose excreted in urine as conjugates and about 6% in feces. The long effective half-life of an injection therefore comes from slow release out of the oil depot, not from slow clearance.
The current US labels do not give an ester half-life. A review of androgen therapy cites a half-life of approximately 4.5 days (Rey & Grinspon, Am J Mens Health 2020).
Intramuscular injection
An IM injection produces a high early peak and a steady decline. The same review summarizes the profile after a single 250 mg injection in young hypogonadal men:
| Time after injection | Serum testosterone |
|---|---|
| Day 7 | 700–1,800 ng/dL (supraphysiologic in many men) |
| Day 14 | 260–700 ng/dL |
| Day 21 | Roughly 100–400 ng/dL (mostly below normal) |
An older kinetic study gave hypogonadal and eugonadal men a single 100 mg or 200 mg IM dose (Sokol et al., Fertil Steril 1982). In the hypogonadal men, 200 mg kept testosterone and estradiol in the normal range through day 11, and 100 mg kept testosterone normal through day 7. The authors recommended 200 mg every 10–14 days for replacement. The label allows 2–4 weeks, which means levels often fall below normal before the next dose at the longer intervals.
Weekly subcutaneous injection (Xyosted)
Smaller weekly doses flatten the curve. At week 12 in the registration trial, the label reports these values for total testosterone (Xyosted label):
| Parameter (n = 137) | Mean (SD) |
|---|---|
| Average concentration over the week | 553 (127) ng/dL |
| Peak concentration | 790 (215) ng/dL |
| Time to peak | 11.9 h (median) |
| Trough concentration | 436 (109) ng/dL |
Steady state was reached by week 6. The mean DHT-to-testosterone ratio before the week-12 dose was 0.07, which the label describes as within the normal range.
Approved medical use
The generic IM label lists three uses (generic label):
| Indication | Labeled dose |
|---|---|
| Male hypogonadism (primary or hypogonadotropic, congenital or acquired) | 50–400 mg every 2–4 weeks |
| Delayed puberty in carefully selected boys | 50–200 mg every 2–4 weeks for a limited time, for example 4–6 months |
| Inoperable metastatic breast cancer in women, 1–5 years postmenopausal (secondary therapy) | 200–400 mg every 2–4 weeks |
The label adds that total doses above 400 mg per month are generally not needed and that injections more often than every two weeks are rarely indicated. Before treating hypogonadism, morning testosterone should be low on at least two separate days. Safety and efficacy in “age-related hypogonadism” have not been established.
For boys with delayed puberty, the label calls for an X-ray of the hand and wrist every six months. Androgens can speed up bone maturation and close the growth plates early, which can reduce adult height.
Xyosted is approved only for adult men with primary or hypogonadotropic hypogonadism. It starts at 75 mg weekly. The dose is then adjusted by 25 mg based on the trough (pre-dose) testosterone after 6 weeks, aiming for 350–650 ng/dL. Its label states that safety and efficacy have not been established under age 18.
The Endocrine Society recommends testosterone therapy only for men with symptoms of deficiency and consistently low morning testosterone, aiming for levels in the mid-normal range (Bhasin et al., JCEM 2018).
What the research shows
Replacement therapy with weekly autoinjection
The Xyosted registration study was a 52-week, open-label, single-arm trial in 150 men with hypogonadism (Kaminetsky et al., J Urol 2019). According to the label, 135 of 150 men (90%) had an average weekly testosterone within the normal range (300–1,100 ng/dL) at week 12, and none had a peak above 1,500 ng/dL. The published paper reports 92.7% for the same endpoint. Mean trough testosterone at week 52 was 487 ng/dL. A second, 26-week safety study enrolled 133 men (Gittelman et al., J Sex Med 2019).
Neither study had a placebo or comparator arm, so they show that the product reaches target levels, not how it compares with other formulations on symptoms.
Supraphysiologic doses and muscle
In a randomized, placebo-controlled trial, 43 healthy men received 600 mg/week testosterone enanthate or placebo for 10 weeks, with or without supervised strength training (Bhasin et al., NEJM 1996):
| Outcome | Placebo, no exercise | Testosterone, no exercise | Testosterone + exercise |
|---|---|---|---|
| Triceps cross-sectional area | −81 mm² | +424 mm² | +501 mm² |
| Quadriceps cross-sectional area | −131 mm² | +607 mm² | +1,174 mm² |
| Bench press | −1 kg | +9 kg | +22 kg |
| Squat | +3 kg | +16 kg | +38 kg |
Testosterone alone, without training, increased muscle size and strength more than placebo. The combination produced the largest gains, including +6.1 kg of fat-free mass. Neither mood nor behavior changed in any group.
The dose-response curve
A follow-up trial suppressed the men’s own testosterone with a GnRH agonist, then randomized 61 young men to one of five weekly testosterone enanthate doses for 20 weeks (Bhasin et al., AJP-Endo 2001):
| Weekly dose | Mean trough testosterone | Fat-free mass change |
|---|---|---|
| 25 mg | 253 ng/dL | — |
| 50 mg | 306 ng/dL | — |
| 125 mg | 542 ng/dL | +3.4 kg |
| 300 mg | 1,345 ng/dL | +5.2 kg |
| 600 mg | 2,370 ng/dL | +7.9 kg |
Fat-free mass increased at the 125, 300 and 600 mg doses, and the gain correlated with the logarithm of the testosterone level (r = 0.73). Leg strength, muscle volume, hemoglobin and IGF-1 rose with dose, while fat mass and HDL cholesterol fell. Sexual function, mood and PSA did not change significantly at any dose.
A secondary analysis that added 60 older men (aged 60–75) found that hemoglobin and hematocrit rose linearly with dose in both age groups, and more steeply in the older men (Coviello et al., JCEM 2008).
Mood and aggression
A companion report from the same 43-man, 10-week trial at 600 mg/week found no difference between testosterone and placebo on any of five anger scales. Ratings by spouses or partners also showed no change (Tricker et al., JCEM 1996). The authors note that this does not rule out effects at still higher doses, with multiple steroids, or in men with existing psychiatric illness. The labels list serious psychiatric reactions, including mania, psychosis and aggression, among reports from people misusing AAS.
Male contraception studies
Testosterone enanthate at 200 mg IM weekly was the regimen in the WHO’s male contraception trials. These trials are the best data on how strongly it suppresses sperm production:
- 1990 trial (271 men): 157 became azoospermic (no sperm in the ejaculate), a cumulative 65% by 6 months, after a mean of 120 days. There was 1 pregnancy in 1,486 months of use, or 0.8 per 100 person-years (95% CI 0.02–4.5) (WHO Task Force, Lancet 1990).
- 1996 trial (399 men): when sperm counts were suppressed to 3 million/mL or fewer, the pregnancy rate was 1.4 per 100 person-years (95% CI 0.4–3.7). 35 men stopped for medical reasons (WHO Task Force, Fertil Steril 1996).
The regimen was never approved as a contraceptive.
Side effects and risks
Labeling history and blood pressure
Xyosted’s label previously carried a boxed warning about blood pressure increases. The current label lists that boxed warning as removed in March 2025. Blood pressure remains a standard warning on both the Xyosted and generic labels.
In the 6-month Xyosted study, 24-hour ambulatory monitoring in 62 men showed average increases of 3.9 mm Hg systolic (95% CI 1.4–6.4) and 1.5 mm Hg diastolic (95% CI 0.4–2.6) after 12 weeks. During the 1-year study, 10% of men started or changed blood pressure medication. Both labels say testosterone is not recommended in uncontrolled hypertension.
Cardiovascular events
The Xyosted label now includes results from TRAVERSE, a randomized trial of 5,198 hypogonadal men aged 45–80 with heart disease or several risk factors. TRAVERSE used testosterone gel, not enanthate. Major adverse cardiovascular events occurred in 7.0% on testosterone and 7.3% on placebo (hazard ratio 0.96, 95% CI 0.78–1.17), meeting the test for noninferiority. Some events were more frequent with testosterone:
| Event | Testosterone gel | Placebo |
|---|---|---|
| Venous thromboembolism | 1.7% | 1.2% |
| Atrial fibrillation | 3.5% | 2.4% |
| Acute kidney injury | 2.3% | 1.5% |
| Bone fracture | 3.5% | 2.5% |
TRAVERSE did not test injectable testosterone, which produces higher peaks. Both labels also note postmarketing reports of deep vein thrombosis and pulmonary embolism.
Erythrocytosis (high hematocrit)
Hematocrit (the share of blood made up of red cells) rises on all testosterone products. A network meta-analysis of 29 randomized trials (3,393 men) estimated these mean increases compared with placebo (Nackeeran et al., J Urol 2022):
| Formulation | Mean hematocrit rise vs placebo (95% CI) |
|---|---|
| IM enanthate / cypionate | +4.0% (2.9–5.1) |
| Oral undecanoate | +4.3% (0.7–8.0) |
| Transdermal gel | +3.0% (1.8–4.3) |
| IM undecanoate | +1.6% (0.3–3.0) |
| Patch | +1.4% (0.2–2.6) |
In the two Xyosted studies (283 men), mean hematocrit rose by 3.8% at 6 months and 5.4% at 1 year. 4.2% of men reached a hematocrit of 55% or higher. The label advises checking hematocrit about every 3 months and stopping treatment if it becomes elevated.
Adverse reactions in the Xyosted trials
The most common reactions in the 1-year study (150 men) were:
| Reaction | Rate |
|---|---|
| Hematocrit increased | 14.0% |
| Hypertension | 12.7% |
| PSA increased | 12.0% |
| Injection-site bruising | 6.7% |
| Headache | 5.3% |
Across both studies, PSA increases led to discontinuation in 4.6% of men. Four men (1.4%) had depression requiring discontinuation or a suicide attempt, one of them fatal. The label now carries a warning on depression and suicidal ideation.
Fertility
Exogenous testosterone shuts down the hormones (LH and FSH) that drive the testes. This lowers the testes’ own testosterone production and can stop sperm production. In the WHO trials, men who reached azoospermia took a median of 3.7 months to recover to at least 20 million sperm/mL, and 6.7 months to return to their own baseline (WHO Task Force, Lancet 1990).
An analysis of 1,549 men from 30 hormonal contraception studies found the following probabilities of recovering to 20 million/mL (Liu et al., Lancet 2006):
- 67% within 6 months;
- 90% within 12 months;
- 96% within 16 months;
- 100% within 24 months.
These were healthy volunteers on controlled doses for limited periods. The Xyosted label warns that the impact on fertility in men on replacement therapy may be irreversible.
Liver and lipids
“Injectables are liver-safe” is an overstatement. Liver toxicity is far more strongly tied to oral 17α-alkylated steroids. Still, the Xyosted label states that long-term IM testosterone enanthate, which keeps blood levels raised for long periods, “has produced multiple hepatic adenomas.” The generic label warns of peliosis hepatis and liver tumors with prolonged high doses.
Lipid effects differ from oral steroids. In a 6-week crossover study in 11 male weightlifters, testosterone enanthate 200 mg/week lowered HDL cholesterol by 9% and LDL by 16%. Oral stanozolol 6 mg/day lowered HDL by 33% and raised LDL by 29% (Thompson et al., JAMA 1989). At higher doses, HDL falls further, as the 2001 dose-response trial showed.
Other labeled warnings
- Prostate. Worsening of benign prostatic hyperplasia and a possible increased risk of prostate cancer.
- Edema. Salt and water retention, which can cause heart failure in people with heart, kidney or liver disease.
- Gynecomastia. Breast enlargement may develop and persist.
- Sleep apnea. May worsen, especially with obesity or chronic lung disease.
- Virilization in women. Voice deepening, facial hair and clitoral enlargement, which may be permanent.
- Post-injection cough. The generic label reports rare cases of an urge to cough, coughing fits and breathing difficulty immediately after injection of the oil.
Interactions
The labels list these interactions:
- Warfarin and other oral anticoagulants: androgens can change anticoagulant effect, so INR should be checked more often when testosterone is started or stopped.
- Insulin and diabetes drugs: blood glucose may fall, and doses may need lowering.
- Corticosteroids: more fluid retention.
- Medicines that raise blood pressure: additive increases, per the Xyosted label.
Who should not use it
Both labels list these contraindications:
- breast cancer in men;
- known or suspected prostate cancer;
- pregnancy, because testosterone can virilize a female fetus;
- hypersensitivity to the product, including its sesame oil.
The Endocrine Society also advises against starting testosterone in several situations, including:
- men planning fertility in the near term;
- PSA above 4 ng/mL, or above 3 ng/mL in higher-risk men, without urological evaluation;
- elevated hematocrit;
- untreated severe obstructive sleep apnea;
- uncontrolled heart failure;
- a heart attack or stroke within the past 6 months;
- thrombophilia.
Legal status and use outside medicine
In the US, testosterone and its esters are Schedule III anabolic steroids under the Controlled Substances Act (21 CFR 1308.13). The labels describe misuse by athletes and bodybuilders, often at high doses and combined with other AAS. They list serious reactions reported with misuse:
- cardiac arrest, heart attack, cardiomyopathy and stroke;
- liver toxicity;
- major depression, mania and psychosis.
The labels also describe a withdrawal syndrome after stopping high doses. It can last weeks to months and includes depressed mood, fatigue and hypogonadism.
Under the WADA 2026 Prohibited List, testosterone and its esters are anabolic androgenic steroids (class S1.1). They are prohibited in and out of competition and are non-specified substances.
Key takeaways
- Plain testosterone, slow release. The enanthate ester only controls how fast testosterone leaves the oil depot. About 72% of the labeled milligrams is testosterone.
- Peaks and troughs with IM dosing. A single IM dose peaks within the first week and drifts below normal by about 3 weeks. Weekly subcutaneous dosing (Xyosted) keeps levels much flatter.
- The research workhorse. Most dose-response, muscle and male-contraception data for testosterone come from this ester. Lean mass rose with the logarithm of the dose, from +3.4 kg at 125 mg/week to +7.9 kg at 600 mg/week.
- Hematocrit and blood pressure are the main things to watch. IM enanthate/cypionate raised hematocrit by about 4 points versus placebo. Weekly autoinjection raised 24-hour systolic pressure by about 4 mm Hg.
- Sperm production is strongly suppressed. 200 mg weekly made about two-thirds of men azoospermic within 6 months. Recovery usually takes months, and the Xyosted label warns the effect may be irreversible.
Sources
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