Testosterone cypionate is testosterone with a cyclopentylpropionate ester attached. The ester lets it sit in an oil depot after intramuscular injection and release slowly. In the US it is the most widely prescribed injectable for testosterone replacement therapy (TRT), sold as Pfizer’s Depo-Testosterone and as generics. It is also one of the most common anabolic-androgenic steroids (AAS) used outside medicine.
This page summarizes what the FDA label, clinical trials and the Endocrine Society guideline actually report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Androgen; anabolic-androgenic steroid |
| Brand / ANDA | Depo-Testosterone (Pfizer), ANDA 085635; generics available |
| Route | Intramuscular (deep gluteal) |
| Strengths | 100 mg/mL and 200 mg/mL in cottonseed oil |
| Labeled dose | 50–400 mg every 2–4 weeks |
| Half-life (label) | About 8 days |
| Testosterone content | About 70% of the ester’s weight (200 mg ester ≈ 140 mg testosterone) |
| US schedule | Controlled substance, Schedule III |
What it is
Chemically, testosterone cypionate is the 17β-cyclopentylpropionate ester of testosterone, formula C₂₇H₄₀O₃, molecular weight 412.6 g/mol (FDA label; PubChem). Testosterone on its own weighs 288.4 g/mol. The ester therefore makes up about 30% of the dose’s weight, so a “200 mg” injection delivers about 140 mg of testosterone.
The ester has no hormonal activity of its own. Esterases in the blood cleave it off and release ordinary testosterone. The ester only changes how fast that happens, by making the molecule more fat-soluble so it leaves the oil depot slowly.
The labeled formulation contains, per mL:
| Ingredient | 100 mg/mL vial | 200 mg/mL vial |
|---|---|---|
| Testosterone cypionate | 100 mg | 200 mg |
| Benzyl benzoate (solubilizer) | 0.1 mL | 0.2 mL |
| Cottonseed oil (carrier) | 736 mg | 560 mg |
| Benzyl alcohol (preservative) | 9.45 mg | 9.45 mg |
How it behaves in the body
After release, testosterone binds the androgen receptor directly. Some is also converted to two more active hormones:
- dihydrotestosterone (DHT), by 5α-reductase;
- estradiol, by aromatase.
This explains why testosterone has effects on muscle, the prostate, hair, the red cell count and estrogen-linked tissue such as breast.
The best-known kinetic study gave 11 hypogonadal men a single 200 mg IM injection of the cypionate (Nankin 1987):
| Measure | Peak rise vs baseline | Timing of peak |
|---|---|---|
| Total testosterone | About 3× | Days 2–5 |
| Free testosterone | About 4.5× | Days 2–3 |
| Non-SHBG-bound testosterone | About 6× | Days 4–5 |
| Estradiol | About 3× | Tracks testosterone |
Many of the men were above the normal range on days 2–7, and levels fell back to baseline by days 13–14. This is the classic peak-and-trough pattern of a two-week schedule. It is why many prescribers now split the same weekly amount into smaller, more frequent injections. The label describes the half-life as about eight days.
Approved medical use
The FDA label covers replacement therapy in males with either of the following, congenital or acquired:
- primary hypogonadism (testicular failure);
- hypogonadotropic hypogonadism (pituitary or hypothalamic failure).
The diagnosis should be confirmed with morning testosterone measured on at least two separate days. The label also states that safety and efficacy have not been established for “age-related hypogonadism,” or for enhancing athletic performance.
The labeled dose is wide, 50–400 mg every 2–4 weeks. The Endocrine Society aims for testosterone in the mid-normal range. For cypionate and enanthate it recommends measuring testosterone midway between injections, and adjusting the dose or interval if that value is above 600 ng/dL or below 350 ng/dL (Bhasin et al., JCEM 2018).
What the research shows on muscle and strength
Most controlled data on muscle come from testosterone enanthate. Once the ester is cleaved, it delivers the same hormone as cypionate on a very similar timescale. The results therefore apply to cypionate in terms of the testosterone dose.
Supraphysiologic doses in trained men
In a landmark trial, 43 men with weightlifting experience received either 600 mg/week testosterone enanthate or placebo for 10 weeks, with or without a supervised training program (Bhasin et al., NEJM 1996):
| Group | Fat-free mass | Bench press 1RM | Squat 1RM |
|---|---|---|---|
| Placebo, no exercise | +0.8 kg | −1 kg | +3 kg |
| Testosterone, no exercise | +3.2 kg | +9 kg | +16 kg |
| Placebo + exercise | +1.9 kg | — | — |
| Testosterone + exercise | +6.1 kg | +22 kg | +38 kg |
Two points stand out:
- Testosterone alone, with no training, added more lean mass than training alone.
- The combination added the most.
Cross-sectional area of the quadriceps rose by 1,174 mm² in the testosterone-plus-exercise group. The investigators found no change in mood or behavior in this setting.
The dose-response curve
The 2001 follow-up first suppressed the participants’ own testosterone with a GnRH agonist. It then gave 61 young men one of five fixed weekly doses of testosterone enanthate for 20 weeks, without a training program (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 gain tracked the logarithm of the testosterone level (r = 0.73). In other words, each doubling of the level bought a roughly similar increment of lean mass.
As the dose went up, fat mass and HDL (“good”) cholesterol fell and hemoglobin rose. A companion analysis showed that hemoglobin and hematocrit climbed in line with the dose, and more steeply in older men (Coviello et al., JCEM 2008).
Side effects and risks
Erythrocytosis (high hematocrit)
A rise in red blood cell mass is the most common lab abnormality on testosterone. Short-acting injectables cause the largest rise.
| Formulation | Mean hematocrit rise vs placebo (95% CI) |
|---|---|
| IM enanthate / cypionate | +4.0% (2.9–5.1) |
| Oral undecanoate | +4.3% |
| Transdermal gel | +3.0% (1.8–4.3) |
| IM undecanoate | +1.6% |
| Patch | +1.4% |
Network meta-analysis of 29 randomized trials, 3,393 men (Nackeeran et al., J Urol 2022).
A three-year clinical cohort reported a hematocrit above 50% in 66.7% of men on injections, compared with 35.1% on pellets and 12.8% on gels (Pastuszak et al., Sex Med 2015). The injection group was younger and started with higher hematocrit, which partly confounds the comparison.
The Endocrine Society advises holding therapy if hematocrit exceeds 54%. Therapy can restart at a lower dose once it falls, after checking for hypoxia and sleep apnea.
Cardiovascular safety
The largest safety trial, TRAVERSE, randomized 5,246 men aged 45–80 who had hypogonadism and existing or high cardiovascular risk (Lincoff et al., NEJM 2023). Participants received testosterone gel titrated to 350–750 ng/dL, or placebo, and were followed for a mean of 33 months.
| Outcome | Testosterone | Placebo |
|---|---|---|
| Major adverse cardiac events (primary) | 7.0% | 7.3% |
| Atrial fibrillation | 3.5% | 2.4% |
| Acute kidney injury | 2.3% | 1.5% |
| Pulmonary embolism | 0.9% | 0.5% |
The primary result had a hazard ratio of 0.96 (95% CI 0.78–1.17), meeting the trial’s noninferiority goal. TRAVERSE tested a gel kept in the physiologic range. It says nothing directly about injectables at supraphysiologic doses, where hematocrit, blood pressure and lipid effects are larger.
The current Depo-Testosterone label lists the following warnings:
- venous thromboembolism;
- increases in blood pressure;
- edema;
- gynecomastia;
- abuse and dependence.
Fertility and suppression of natural production
External testosterone suppresses LH and FSH, the pituitary signals that drive the testes. This shuts down sperm production, and the effect is strong enough that testosterone has been studied as a male contraceptive.
In a WHO trial, 271 men received 200 mg/week testosterone enanthate (WHO Task Force, Lancet 1990):
- 65% had no sperm at all (azoospermia) by 6 months;
- the mean time to reach azoospermia was 120 days.
Recovery after stopping is usually complete but takes months. An integrated analysis of 1,549 men in hormonal-contraception studies found the following (Liu et al., Lancet 2006):
| Time after stopping | Recovered to ≥20 million/mL |
|---|---|
| 6 months | 67% |
| 12 months | 90% |
| 16 months | 96% |
| 24 months | 100% |
The median time to recovery was 3.4 months. Recovery was slower after longer treatment and after longer-acting preparations. Note that these are contraceptive-trial doses; recovery after years of high-dose, multi-compound use is less well studied. The Endocrine Society advises against starting testosterone in men planning a pregnancy in the near term.
Who should not use it
The label contraindicates it in men with:
- breast cancer, or known or suspected prostate cancer;
- serious cardiac, hepatic or renal disease.
It is also contraindicated in pregnancy. The Endocrine Society additionally advises against starting therapy in men with any of the following:
- PSA above 4 ng/mL (above 3 ng/mL in higher-risk men);
- baseline hematocrit above 48%;
- a heart attack or stroke within the past 6 months;
- thrombophilia.
Monitoring on therapy
These are the Endocrine Society checkpoints for men on testosterone:
| What | When |
|---|---|
| Testosterone (mid-interval for cypionate) | 3–6 months after starting, and after dose changes |
| Hematocrit | Baseline, 3–6 months, then yearly |
| PSA and prostate exam (age-eligible men) | Baseline, 3–12 months, then per prostate screening guidelines |
| Symptom response and side effects | 3–12 months, then yearly |
Legal status and use outside medicine
In the US, testosterone cypionate has been a Schedule III controlled substance since the Anabolic Steroid Control Act of 1990, so it needs a prescription.
A meta-analysis of 187 studies estimated the following global lifetime prevalence of AAS use (Sagoe et al., Ann Epidemiol 2014):
- 3.3% overall;
- 6.4% among men;
- 1.6% among women.
Testosterone esters are the backbone of most non-medical use. Product bought outside a pharmacy is not regulated for dose, sterility or identity.
Key takeaways
- Same hormone, slow release. Cypionate is plain testosterone with an ester that sets the release rate. About 70% of the labeled milligrams is testosterone.
- Peaks and troughs. A single 200 mg dose peaks in 2–5 days and returns to baseline by about 2 weeks. Shorter dosing intervals smooth this out.
- Dose-dependent effects. Lean-mass gains rise with the logarithm of the testosterone level. Hematocrit rises and HDL falls with dose as well.
- Hematocrit is the main lab to watch. Injectables raise it more than gels or patches, and 54% is the guideline threshold for holding therapy.
- Fertility is suppressed. Sperm production usually recovers after stopping, but typically over months, not weeks.
Sources
- Pfizer. Depo-Testosterone (testosterone cypionate) injection, prescribing information. DailyMed; Drugs@FDA, ANDA 085635.
- National Center for Biotechnology Information. Testosterone cypionate, PubChem CID 441404. PubChem.
- Nankin HR. Hormone kinetics after intramuscular testosterone cypionate. Fertil Steril. 1987;47(6):1004–1009. PubMed.
- Bhasin S, Storer TW, Berman N, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996;335(1):1–7. PubMed.
- Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281(6):E1172–E1181. PubMed.
- Coviello AD, Kaplan B, Lakshman KM, et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914–919. PubMed.
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. JCEM.
- Nackeeran S, Kohn T, Gonzalez D, et al. The effect of route of testosterone on changes in hematocrit: a systematic review and Bayesian network meta-analysis of randomized trials. J Urol. 2022;207(1):44–51. PubMed.
- Pastuszak AW, Gomez LP, Scovell JM, et al. Comparison of the effects of testosterone gels, injections, and pellets on serum hormones, erythrocytosis, lipids, and prostate-specific antigen. Sex Med. 2015;3(3):165–173. PubMed.
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107–117. PubMed.
- World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet. 1990;336(8721):955–959. PubMed.
- Liu PY, Swerdloff RS, Christenson PD, et al. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006;367(9520):1412–1420. PubMed.
- Sagoe D, Molde H, Andreassen CS, Torsheim T, Pallesen S. The global epidemiology of anabolic-androgenic steroid use: a meta-analysis and meta-regression analysis. Ann Epidemiol. 2014;24(5):383–398. PubMed.