“Testosterone base” means testosterone itself: the hormone with no ester attached. Chemists use “base” for the parent molecule, as opposed to esters such as cypionate or enanthate. Every milligram is testosterone, and nothing has to be cleaved off before it can act.
Unesterified testosterone is the active ingredient in several US testosterone medicines: skin gels such as AndroGel, the nasal gel Natesto and the implanted pellet Testopel. Injectable forms of unesterified testosterone once had US approvals, but Drugs@FDA lists all of them as discontinued. In the US, products sold today as injectable “testosterone base”, in water or oil, come from outside the regulated drug supply. The defining fact about the free hormone is how briefly it lasts: FDA labels give a half-life in blood of 10–100 minutes.
This page summarizes what FDA labels, clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Androgen; the parent anabolic-androgenic steroid (AAS) |
| Chemistry | C₁₉H₂₈O₂, 288.4 g/mol; 100% of the labeled dose is testosterone |
| Solubility | About 23.4 mg/L in water; soluble in vegetable oils and alcohol |
| US products (current) | Transdermal gels and solution (e.g. AndroGel), nasal gel (Natesto), subcutaneous pellets (Testopel) |
| US injectables | Three unesterified testosterone injectables (25, 50 and 100 mg/mL) listed as discontinued |
| Half-life in blood (label) | 10–100 minutes |
| By mouth | Inactivated by the liver before reaching the circulation |
| US schedule | Controlled substance, Schedule III |
| WADA status | Prohibited at all times (S1.1, when administered exogenously) |
What it is
Testosterone is 17β-hydroxyandrost-4-en-3-one, formula C₁₉H₂₈O₂, molecular weight 288.4 g/mol (PubChem). PubChem lists its water solubility as about 23.4 mg/L at 25 °C. It dissolves readily in alcohol and vegetable oils. That poor water solubility is why an injectable “in water” is a suspension of crystals rather than a solution.
In 1935, Ernst Laqueur’s group in Amsterdam isolated testosterone, and Adolf Butenandt and Leopold Ruzicka synthesized it (Nieschlag & Nieschlag, Eur J Endocrinol 2019). The same history notes the central problem with the free hormone: swallowed testosterone is inactivated in the liver. Much of the later drug development, including esters, implants, patches and gels, was a search for ways around that and around its short life in blood.
All testosterone esters work by releasing this molecule. The ester changes only how fast testosterone leaves the injection site:
| Form | What is injected or applied | Testosterone share of labeled dose | Library page |
|---|---|---|---|
| Unesterified (“base”) | Testosterone itself | 100% | This page |
| Aqueous suspension | Unesterified testosterone crystals in water | 100% | Testosterone Suspension |
| Short ester | Testosterone propionate | Less than 100% | Testosterone Propionate |
| Long esters | Cypionate, enanthate | Less than 100% | Testosterone Cypionate, Testosterone Enanthate |
| Transdermal | Unesterified testosterone in a gel applied to skin | 100% | Testosterone Gel |
The library also has a separate page for testosterone suspension, which is the water-based form of the same unesterified hormone.
“Cleaner” testosterone? Unesterified testosterone is sometimes described as a different or “cleaner” steroid than the esters. It is not. It is the same molecule every ester releases. FDA labels state that testosterone’s major active metabolites are estradiol and dihydrotestosterone (DHT), regardless of formulation (AndroGel label). What differs between forms is timing, not the hormone.
How it behaves in the body
Once in the blood, testosterone acts on the androgen receptor and is converted to DHT and estradiol. The AndroGel 1.62% label describes its handling in the body:
- Binding: about 40% is bound to sex hormone-binding globulin (SHBG), about 2% is free, and the rest is loosely bound to albumin and other proteins.
- Half-life: reported half-lives in the literature range from 10 to 100 minutes.
- Excretion: about 90% of an intramuscular dose leaves in the urine as glucuronide and sulfate conjugates, and about 6% in the feces.
For scale, a stable-isotope study measured how much testosterone men make each day (Wang et al., JCEM 2004). Young white men produced 9.11 mg/day and young Asian men 7.22 mg/day, and middle-aged white men 3.88 mg/day.
Route decides everything
Because the free hormone is cleared within minutes to hours, how long it acts depends almost entirely on the delivery route:
| Route | Product or study | What happened |
|---|---|---|
| Oral, free testosterone | Nieschlag et al., 1975 | No effect on plasma androgen levels (inactivated by the liver) |
| Sublingual (cyclodextrin), 2.5 or 5 mg | Salehian et al., JCEM 1995, 63 hypogonadal men | Peak at 20 min; back to baseline by 360 min; half-life ≈60–69 min |
| Nasal gel, 11 mg | Natesto label | Peak at ≈40 min; half-life 10–100 min; dosed three times daily |
| Transdermal gel | AndroGel 1.62% label | Skin acts as a reservoir; continuous delivery over 24 h with once-daily use |
| Subcutaneous pellets, 75 mg each | Testopel label | Labeled 150–450 mg every 3–6 months |
| Intramuscular microspheres (experimental) | Burris et al., Fertil Steril 1988, 8 men | Biphasic release: rises in week 1 and again in weeks 6–11 |
The 1975 study compared free testosterone with testosterone undecanoate taken by mouth. Free testosterone did nothing to plasma androgens, while the undecanoate raised them. The authors attributed this to undecanoate being absorbed through the lymph, bypassing the liver (see oral testosterone undecanoate).
We found no published pharmacokinetic study of a plain intramuscular injection of unesterified testosterone, in water or oil, in humans. Any timing figures for injectable “testosterone base” should be treated as unverified.
Approved medical use
In the US, unesterified testosterone is approved only in non-injected forms. The AndroGel 1.62%, Natesto and Testopel labels cover replacement therapy in males (adult males for AndroGel and Natesto) with primary hypogonadism (testicular failure) or hypogonadotropic hypogonadism (pituitary or hypothalamic failure). The labels state that:
- the diagnosis should be confirmed with low morning testosterone on at least two separate days;
- safety and efficacy in “age-related hypogonadism” have not been established (AndroGel 1.62%);
- the product has not been shown to be safe and effective for enhancing athletic performance (Testopel).
Labeled doses:
| Product | Labeled dose |
|---|---|
| AndroGel 1.62% | Start 40.5 mg testosterone once daily; adjustable from 20.25 to 81 mg |
| Natesto nasal gel | 11 mg per dose (one spray per nostril), three times daily (33 mg/day) |
| Testopel pellets | 150–450 mg subcutaneously every 3–6 months |
Drugs@FDA lists three injectable products containing only unesterified testosterone, at 25, 50 and 100 mg/mL. All three are marked discontinued (Drugs@FDA, ANDA 086417), and Drugs@FDA does not post a label for the 100 mg/mL product.
The Endocrine Society recommends aiming for testosterone in the mid-normal range with any approved formulation (Bhasin et al., JCEM 2018).
What the research shows
Controlled trials of unesterified testosterone are trials of gels, nasal gel and other non-injected forms. These deliver roughly physiologic doses, so the results describe replacement therapy, not high-dose use.
Reaching normal levels
| Trial | Design | Result |
|---|---|---|
| AndroGel 1.62% pivotal trial | Randomized, double-blind, placebo-controlled; 274 hypogonadal men; 182 days | 81.6% (146/179) had average testosterone of 300–1000 ng/dL at day 112 |
| Natesto pivotal trial | Open-label; 306 hypogonadal men; 90 days | 90% of 73 men on 11 mg three times daily had average testosterone of 300–1050 ng/dL at day 90 |
| Sublingual cyclodextrin vs enanthate | 63 hypogonadal men; 60 days | Sexual motivation and performance improved in all groups, despite 2–4 times lower testosterone exposure than with 200 mg enanthate |
Sources: AndroGel 1.62% label; Natesto label; Salehian et al., JCEM 1995.
In the sublingual study, LH and FSH were suppressed more with enanthate injections than with the short-acting sublingual form. Hematocrit rose with enanthate but not with sublingual testosterone.
Older men: the Testosterone Trials
The T Trials gave 790 men aged 65 or older, with testosterone under 275 ng/dL and symptoms, either testosterone gel or placebo gel for 1 year (Snyder et al., NEJM 2016). Testosterone was raised to the mid-normal range for young men.
| Outcome | Result |
|---|---|
| Sexual activity, desire, erectile function | Significantly improved |
| Walking distance (gain of at least 50 m in 6 minutes) | 20.5% vs 12.6% across all participants (p = 0.003); not significant in the Physical Function Trial alone |
| Vitality (fatigue scale) | No significant benefit |
| Mood and depressive symptoms | Slightly better |
The authors noted that the trials were too small to draw conclusions about risks.
Cardiovascular safety: TRAVERSE
TRAVERSE randomized 5,246 men aged 45–80 with hypogonadism and existing or high cardiovascular risk to 1.62% testosterone gel or placebo gel (Lincoff et al., NEJM 2023). Doses were adjusted to keep testosterone at 350–750 ng/dL, and mean follow-up was 33 months.
- Major adverse cardiac events occurred in 7.0% vs 7.3% (hazard ratio 0.96, 95% CI 0.78–1.17), meeting the noninferiority goal.
- Atrial fibrillation, acute kidney injury and pulmonary embolism were more frequent with testosterone.
TRAVERSE tested physiologic levels from a gel. It does not show safety at the higher doses used outside medicine.
Detection in sport
Because testosterone is also made by the body, testing has to tell a dose apart from natural production. Short-acting forms leave a brief signal:
- Nasal gel in men: five active men used Natesto three times daily (Miller et al., Drug Test Anal 2016). In the first 24 hours after a dose, 70% of urine samples had a suspicious steroid profile and isotope testing confirmed exogenous testosterone in 90%. At 24–48 hours, those figures fell to 0% and 40%.
- Low-dose gel in women: twelve women applied 12.5 mg testosterone gel daily for 7 days (Savkovic et al., Drug Test Anal 2022). The urine testosterone/epitestosterone ratio rose only briefly (2–4 days), and carbon isotope testing did not discriminate. A model combining serum, urine and reticulocyte measures classified 93% of cases correctly.
Side effects and risks
Boxed warning for gels: secondary exposure
The AndroGel 1.62% label carries a boxed warning. Children have been virilized after contact with skin where a man applied testosterone gel. Reported signs included:
- enlargement of the penis or clitoris;
- pubic hair;
- increased erections and libido, and aggressive behavior;
- advanced bone age.
Most cases regressed once exposure ended, but in a few, genital size and bone age did not fully return to normal. Gels are also contraindicated in pregnant women because testosterone can virilize a female fetus.
Labeled warnings
The AndroGel 1.62% label lists these warnings, which apply to testosterone in general:
- Polycythemia: hematocrit (the share of blood made up of red cells) can rise. The label advises checking it before treatment, at 3–6 months and then yearly, and stopping therapy if it becomes elevated.
- Blood pressure: on ambulatory monitoring, average blood pressure rose by 1.9/1.3 mm Hg after 16 weeks, and by 3.0/2.2 mm Hg in men already treated for hypertension.
- Venous thromboembolism: postmarketing reports of blood clots in the veins.
- Prostate: possible worsening of benign prostatic hyperplasia and risk of prostate cancer.
- Fertility: large doses can suppress sperm production through feedback on the pituitary.
- Other: edema, gynecomastia, sleep apnea, lipid changes.
The Testopel label adds implant-site infection and pellet extrusion, mostly within the first month after insertion.
Abuse-related harm
The labels state that testosterone is abused, usually at higher doses and combined with other AAS. Serious reactions reported in people abusing AAS include:
- cardiac arrest, heart attack, cardiomyopathy and stroke;
- liver toxicity;
- major depression, mania, psychosis and aggression;
- testicular atrophy and infertility in men;
- virilization, voice deepening and menstrual changes in women;
- early closure of growth plates in adolescents.
The label notes that these reports cannot reliably establish frequency or cause.
Quality of products outside pharmacies
No approved unesterified testosterone injection is currently marketed in the US, so injectable “testosterone base” is unregulated for content, dose and sterility. In one forensic analysis of 328 seized steroid medicines in Brazil, about 42% were counterfeit, including 12.0% of aqueous suspensions and 65.2% of oil solutions (Neves & Caldas, Forensic Sci Int 2017). That study covered several steroids, not unesterified testosterone alone.
Who should not use it
The AndroGel 1.62% label contraindicates testosterone in men with breast cancer or known or suspected prostate cancer, and in pregnant women. The Endocrine Society also advises against starting therapy in men who plan fertility soon, or who have any of the following:
- PSA above 4 ng/mL (above 3 ng/mL in higher-risk men) without further evaluation;
- elevated hematocrit or untreated severe sleep apnea;
- uncontrolled heart failure;
- a heart attack or stroke within the past 6 months, or thrombophilia.
Legal status
- US: testosterone, “including its salts, esters and ethers,” is a Schedule III anabolic steroid (21 CFR 1308.13). It requires a prescription.
- Sport: testosterone is on the WADA 2026 Prohibited List under S1.1 anabolic androgenic steroids “when administered exogenously,” prohibited both in and out of competition.
Key takeaways
- No ester, same hormone. “Testosterone base” is testosterone itself. Every ester releases this molecule, and it converts to DHT and estradiol like any testosterone.
- Very short-lived in blood. Labels give a half-life of 10–100 minutes, and swallowed testosterone is inactivated by the liver.
- Route sets the duration. Approved forms use skin gels, nasal gel or implanted pellets to stretch delivery from minutes to a day or months.
- Injectables are off the US market. All three unesterified testosterone injectables on Drugs@FDA are discontinued, and no human pharmacokinetic study of a plain injection was found.
- Replacement-dose evidence is solid. Gel trials show normalized levels, modest gains in sexual function, and no excess of major cardiac events in TRAVERSE. None of this addresses high doses.
- Controlled and banned in sport. Schedule III in the US and prohibited at all times by WADA.
Sources
- Ascend Therapeutics. AndroGel (testosterone gel) 1.62%, prescribing information. DailyMed.
- Acerus Pharmaceuticals. Natesto (testosterone) nasal gel, prescribing information. DailyMed.
- Endo USA. Testopel (testosterone pellets), prescribing information. DailyMed.
- Food and Drug Administration. Testosterone injectable 100 mg/mL, ANDA 086417 (discontinued). Drugs@FDA.
- National Center for Biotechnology Information. Testosterone, PubChem CID 6013. PubChem.
- Nieschlag E, Nieschlag S. ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019;180(6):R201–R212. PubMed.
- Nieschlag E, Mauss J, Coert A, Kićović P. Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Acta Endocrinol (Copenh). 1975;79(2):366–374. PubMed.
- Salehian B, Wang C, Alexander G, et al. Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate–a clinical research center study. J Clin Endocrinol Metab. 1995;80(12):3567–3575. PubMed.
- Burris AS, Ewing LL, Sherins RJ. Initial trial of slow-release testosterone microspheres in hypogonadal men. Fertil Steril. 1988;50(3):493–497. PubMed.
- Wang C, Catlin DH, Starcevic B, et al. Testosterone metabolic clearance and production rates determined by stable isotope dilution/tandem mass spectrometry in normal men: influence of ethnicity and age. J Clin Endocrinol Metab. 2004;89(6):2936–2941. 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. PubMed.
- Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–624. 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.
- Miller GD, Nair V, Morrison MS, et al. Intranasal delivery of Natesto testosterone gel and its effects on doping markers. Drug Test Anal. 2016;8(11-12):1197–1203. PubMed.
- Savkovic S, Ly LP, Desai R, et al. Detection of testosterone microdosing in healthy females. Drug Test Anal. 2022;14(4):653–666. PubMed.
- Neves DBDJ, Caldas ED. GC-MS quantitative analysis of black market pharmaceutical products containing anabolic androgenic steroids seized by the Brazilian Federal Police. Forensic Sci Int. 2017;275:272–281. PubMed.
- US Drug Enforcement Administration. Schedules of controlled substances: Schedule III, 21 CFR 1308.13. eCFR.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.