Testosterone Enanthate Half-Life: ~4.5 Days
Testosterone heptanoate · ~72% active testosterone by weight · FDA-approved (Delatestryl, Xyosted) · DEA Schedule III · WADA S1 Prohibited
✓ Human PK Study FDA Approved DEA Schedule IIIQuick Reference
| Parameter | Value | Notes |
|---|---|---|
| Plasma half-life | ~4.5 days (108 h) | After IM injection[1] |
| Tmax (IM) | ~2–3 days | Time to peak serum testosterone[1] |
| Active testosterone by weight | ~72% | MW 288.4 / MW 400.6 = 0.720[2] |
| Route | IM or SC injection | IM (Delatestryl); SC weekly (Xyosted) |
| FDA approval (IM) | Delatestryl — NDA 009162 | 200 mg/mL intramuscular |
| FDA approval (SC) | Xyosted — NDA 208271 | 50–100 mg/week autoinjector |
| DEA schedule | Schedule III | Controlled Substances Act |
| WADA detection window | ~3 months | T/E ratio + IRMS[3] |
| Typical TRT interval | Every 7–14 days (IM) / weekly (SC) | Based on ~4.5-day t½ |
| Data Quality | ✓ Human PK Study — Half-life established in controlled human pharmacokinetic studies | |
Ester Weight: How Much Active Testosterone Is in Each Dose?
Testosterone enanthate is not pure testosterone. The enanthate (heptanoate) ester is chemically attached to extend the molecule's half-life by creating a lipophilic depot at the injection site. This ester adds molecular weight but contributes no androgenic activity — it must be cleaved by plasma esterases to release free testosterone.[2]
This calculation matters clinically: a 200 mg/2 mL dose of Delatestryl delivers approximately 144 mg of active testosterone once esterase cleavage is complete. Clinicians using testosterone enanthate for TRT dose based on total ester weight (the labeled concentration), not active testosterone equivalent — the 72% conversion is implicitly accounted for in established dosing protocols.
Pharmacokinetics After Injection
Testosterone enanthate forms a microcrystalline depot at the injection site after IM administration. Esterases in local tissue and circulating plasma hydrolyze the ester bond, releasing free testosterone into systemic circulation at a rate governed by the depot dissolution kinetics.[1]
Key PK Parameters
| Parameter | IM (Delatestryl) | SC Weekly (Xyosted) |
|---|---|---|
| Half-life | ~4.5 days (108 h)[1] | ~4–5 days (comparable) |
| Tmax | ~2–3 days post-injection | ~2–4 days post-injection |
| Bioavailability | ~100% (IM depot) | ~100% (SC depot) |
| Typical dosing interval | Every 7–14 days | Weekly |
| Peak-to-trough variation | High with q14d | Reduced with weekly SC |
Schulte-Beerbuhl and Nieschlag (1980) established the IM half-life in a controlled pharmacokinetic study in healthy males, demonstrating a terminal half-life of approximately 4.5 days and full return toward baseline by approximately 3 weeks after a single 250 mg injection.[1]
Clearance Timeline (t½ = 4.5 days = 108 hours)
Using the established half-life of 4.5 days. Steady-state is reached after approximately 5 half-lives (~22.5 days) with regular dosing.
| Half-Lives Elapsed | Approximate Time | % of Peak Remaining |
|---|---|---|
| 1 t½ | ~4.5 days | 50% |
| 2 t½ | ~9 days | 25% |
| 3 t½ | ~13.5 days | 12.5% |
| 4 t½ | ~18 days | 6.25% |
| 5 t½ | ~22.5 days | <3.1% (effectively cleared) |
WADA Detection Window: ~3 Months
Despite a pharmacokinetic half-life of only 4.5 days, testosterone enanthate is detectable in anti-doping tests for approximately 3 months (12 weeks) after the last injection.[3] This extended detection window reflects the sensitivity of the analytical methods used:
Detection Methods
| Method | What It Detects | Approximate Window |
|---|---|---|
| T/E ratio (urine) | Urinary testosterone-to-epitestosterone ratio >4:1 | ~3–4 weeks post-dose |
| Isotope Ratio Mass Spectrometry (IRMS) | Synthetic ¹³C/¹²C isotope signature vs endogenous T | ~3 months post-dose[3] |
| Longitudinal profiling (ABP) | Atypical passport values vs athlete's baseline | Months to years (indirect) |
IRMS is the confirmatory gold standard. Synthetic testosterone from pharmaceutical sources has a distinct carbon isotope ratio compared to endogenous testosterone produced from cholesterol. WADA Technical Document TD2016IRMS defines the criteria for a confirmatory positive result.[3] This isotopic signature persists in urine long after serum levels have normalized.
Mechanism of Action and Depot Pharmacology
After IM injection, testosterone enanthate precipitates as an oily depot in muscle tissue. Local lipases and non-specific esterases hydrolyze the C-17 enanthate ester, releasing free testosterone that diffuses into systemic circulation. Free testosterone then:[2]
- Binds androgen receptors (AR) in target tissues (muscle, bone, prostate, brain)
- Is aromatized to estradiol in adipose and other tissues by CYP19A1 (aromatase)
- Is reduced to dihydrotestosterone (DHT) by 5α-reductase in skin and prostate
- Suppresses LH and FSH via negative feedback on the hypothalamic-pituitary axis
The enanthate ester's carbon chain length determines the depot dissolution rate and thus the half-life. Longer ester chains (cypionate, undecanoate) produce longer half-lives; shorter chains (propionate) produce shorter half-lives.
Calculate Your TRT Clearance Timeline
Halflife Labs calculates injection-to-injection serum curves based on testosterone enanthate's 4.5-day half-life. Visualize trough timing, steady-state accumulation, and clearance after your last dose.
Download Halflife LabsTestosterone Ester Comparison
| Ester | Half-Life | Active T by Weight | Typical Interval | FDA Approved |
|---|---|---|---|---|
| Testosterone propionate | ~0.8 days | ~83% | Every 2–3 days | Yes (various NDA) |
| Testosterone enanthate | ~4.5 days | ~72% | Every 7–14 days | Yes (NDA 009162, 208271) |
| Testosterone cypionate | ~7 days | ~69% | Every 7–14 days | Yes (Depo-Testosterone NDA 010885) |
| Testosterone undecanoate (IM) | ~21 days | ~63% | Every 10 weeks | Yes (Aveed NDA 022219) |
Related Compounds
| Compound | Relationship | Half-Life |
|---|---|---|
| Gonadorelin | GnRH agonist; used with TRT to preserve LH/FSH signaling | ~2–10 min (IV) |
| HGH (somatropin) | Often co-administered in TRT protocols | ~3–4 h (SC) |
Frequently Asked Questions
What is the half-life of testosterone enanthate?
The plasma half-life of testosterone enanthate after intramuscular injection is approximately 4.5 days (108 hours). This was established in a controlled pharmacokinetic study by Schulte-Beerbuhl and Nieschlag (1980) in healthy adult males receiving 250 mg IM.[1]
How much active testosterone is in testosterone enanthate?
Approximately 72% by molecular weight. Testosterone MW is 288.42 g/mol; testosterone enanthate MW is 400.59 g/mol. Dividing these gives 0.720, meaning each 100 mg of TE delivers ~72 mg of active testosterone once the enanthate ester is cleaved.[2]
Is testosterone enanthate FDA-approved?
Yes. Testosterone enanthate is FDA-approved under NDA 009162 (Delatestryl, IM) and NDA 208271 (Xyosted, SC weekly autoinjector) for testosterone replacement therapy in males with hypogonadism. It is a DEA Schedule III controlled substance.
How long is testosterone enanthate detectable by WADA testing?
Approximately 3 months using isotope ratio mass spectrometry (IRMS), which detects the synthetic carbon isotope signature of pharmaceutical testosterone. The T/E ratio normalizes sooner (~3–4 weeks), but IRMS remains positive for ~12 weeks after the last injection.[3]
How often should testosterone enanthate be injected for TRT?
Typically every 7–14 days (IM) or weekly (SC via Xyosted). Given the 4.5-day half-life, weekly injections produce more stable serum testosterone levels than biweekly injections, which result in significant peak-to-trough variation.
What is the Tmax for testosterone enanthate after injection?
After intramuscular injection, peak serum testosterone (Tmax) occurs approximately 2–3 days post-injection as the enanthate ester undergoes depot dissolution and esterase hydrolysis.[1]
What is the difference between testosterone enanthate and testosterone cypionate?
Testosterone enanthate (t½ ~4.5 days, ~72% active T by weight) and testosterone cypionate (t½ ~7 days, ~69% active T) are both IM androgens used for TRT. Cypionate's longer half-life produces a slower decline between injections. Both are DEA Schedule III and WADA S1 prohibited.
Is testosterone enanthate a controlled substance?
Yes. Testosterone enanthate is a DEA Schedule III controlled substance under the Anabolic Steroid Control Act. Despite FDA approval for medical use, possession without a valid prescription is illegal. It is prohibited in sport under WADA Prohibited List category S1 (Anabolic Agents).
Halflife Labs — TRT Timing Made Visual
Log testosterone enanthate injections, visualize serum curves across injection cycles, and understand steady-state accumulation. Download the free iOS app.
Get the App (iOS)References
- Schulte-Beerbuhl M, Nieschlag E. Comparison of testosterone, dihydrotestosterone, luteinizing hormone, and follicle-stimulating hormone in serum after injection of testosterone enanthate or testosterone cypionate. Fertil Steril. 1980;33(2):201–203. PMID: 7353620
- Testosterone enanthate [prescribing information]. Paddock Laboratories (Delatestryl). NDA 009162. U.S. Food and Drug Administration.
- World Anti-Doping Agency. Technical Document TD2016IRMS: Mass Spectrometry Criteria for the Confirmation of Endogenous Steroids — Testosterone. WADA; 2016. Available at: wada-ama.org
- Xyosted (testosterone enanthate injection) [prescribing information]. Antares Pharma Inc. NDA 208271. FDA approval 2018.
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2010;95(6):2536–2559. PMID: 20525905
- Handelsman DJ. Pharmacology of testosterone preparations. In: Testosterone: Action, Deficiency, Substitution. 4th ed. Cambridge University Press; 2012.