Oral testosterone undecanoate (TU) is testosterone with an 11-carbon fatty-acid ester, packed into soft capsules with oils that help it get absorbed from the gut. Unlike older oral androgens such as methyltestosterone, it is not 17α-alkylated. It releases ordinary testosterone and has not been linked to the liver injury seen with that class.
It was first marketed as Andriol in the mid-1970s and was sold for decades outside the US (Gooren, J Androl 1994). In the US, three newer capsule formulations are FDA-approved for testosterone replacement: Jatenzo (2019), Tlando (2022) and Kyzatrex (2022). The key practical facts are that the capsules must be taken twice daily with food, and that all three US labels warn that they can raise blood pressure.
The same ester is also given as a long-acting injection (Aveed, Nebido), which behaves very differently. It has its own page: testosterone undecanoate injection. This page summarizes what the FDA and European labels, clinical trials and regulators report about the oral capsules. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Androgen; testosterone ester (not 17α-alkylated) |
| US brands / approval | Jatenzo (NDA 206089, March 27, 2019); Tlando (NDA 208088, March 28, 2022); Kyzatrex (NDA 213953, July 27, 2022) |
| Older brand | Andriol / Restandol Testocaps 40 mg (Organon, later MSD); never FDA-approved; Irish licence withdrawn December 31, 2020 |
| Route | Oral soft capsule, taken with meals, usually twice daily |
| Labeled US doses | Jatenzo 158–396 mg twice daily; Tlando 225 mg twice daily; Kyzatrex 100 mg once daily to 400 mg twice daily |
| Half-life | Testosterone undecanoate about 2 h (Tlando label); levels peak about 4–5 h after a dose |
| Testosterone content | About 63% of the ester’s weight (40 mg TU = 25.3 mg testosterone) |
| Absorption | Largely through the intestinal lymphatic system, partly bypassing the liver; strongly food-dependent |
| 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-hydroxyandrost-4-en-3-one undecanoate: formula C₃₀H₄₈O₃, molecular weight 456.7 (Jatenzo label). The European label states that each 40 mg capsule of TU is equivalent to 25.3 mg of testosterone (Restandol Testocaps SmPC).
The ester has no hormonal activity itself. Non-specific esterases cleave it to release testosterone and undecanoic acid, which is broken down like other fatty acids. Testosterone then acts on the androgen receptor directly and is converted to dihydrotestosterone (DHT) and estradiol.
What separates oral TU from other testosterone products is its route into the blood. Drugs absorbed from the gut normally pass through the portal vein to the liver, which can break them down before they reach the rest of the body (first-pass metabolism). TU is very fat-soluble, so part of each dose is packaged into dietary fat particles and absorbed into the lymph vessels of the gut. The lymph drains into the bloodstream through the thoracic duct, skipping the portal vein that leads to the liver (Tlando label). The European label describes this as only partly avoiding first-pass breakdown. In 4 surgical patients with a thoracic duct catheter, radiolabeled oral TU appeared in lymph and plasma at the same time, 2.5–5 h after dosing (Horst et al., Klin Wochenschr 1976). The main compounds in the lymph were TU and 5α-dihydrotestosterone undecanoate (DHTU), and part of the dose was metabolized in the gut wall.
The products differ mainly in the oils and emulsifiers in the capsule:
| Product | Strengths (TU per capsule) | Fill excipients (label) | Labeled dosing |
|---|---|---|---|
| Jatenzo (Tolmar) | 158, 198, 237 mg | Oleic acid, polyoxyl 40 hydrogenated castor oil, borage seed oil, peppermint oil | Start 237 mg twice daily; titrate 158–396 mg twice daily |
| Tlando (Verity) | 112.5 mg | Glyceryl monolinoleate, polyoxyl 40 hydrogenated castor oil, polyethylene glycol 8000, ascorbyl palmitate | 225 mg (2 capsules) twice daily, no titration |
| Kyzatrex (Marius) | 50, 100, 150, 200 mg | Propylene glycol monolaurate, polyoxyl 40 hydrogenated castor oil, vitamin E | Start 200 mg twice daily; titrate from 100 mg once daily to 400 mg twice daily |
| Andriol / Restandol Testocaps (Organon/MSD) | 40 mg | Castor oil, propylene glycol monolaurate | 120–160 mg/day for 2–3 weeks, then 40–120 mg/day, split morning and evening |
Both the Tlando and Kyzatrex labels state that the product is not substitutable with other oral TU products. The milligram doses are not interchangeable between brands.
The original Andriol dissolved TU in oleic acid, which made storage inconvenient. Organon replaced it with the castor-oil “Testocaps” formulation, which is stable at room temperature for about 3 years and was shown to be bioequivalent to the old one (Köhn and Schill, World J Urol 2003).
Pharmacokinetics
Absorption and timing
| Parameter | Value | Source |
|---|---|---|
| Oral bioavailability (Testocaps) | About 7% | Restandol SmPC |
| Time to peak testosterone | About 4–5 h (Testocaps); median about 5 h (Tlando) | Restandol SmPC; Tlando label |
| Peak testosterone after 80–160 mg Testocaps | About 40 nmol/L (≈ 1,150 ng/dL); stays raised for at least 8 h | Restandol SmPC |
| Elimination half-life of TU | About 2 h | Tlando label |
| Half-life of testosterone once released | 10–100 minutes in the literature | Tlando label |
| Dose linearity (Testocaps) | Shown for 40–240 mg/day | Restandol SmPC |
The short half-life is why every product is taken twice daily. Blood testosterone rises and falls within each 12-hour interval, rather than holding steady.
At steady state on the US products, the 24-hour average (Cavg) and peak (Cmax) total testosterone looked like this in the pivotal trials (Jatenzo label; Tlando label; Kyzatrex label):
| Product | Sample type | Mean Cavg | Mean Cmax |
|---|---|---|---|
| Jatenzo (n = 151) | NaF-EDTA plasma | 403 ng/dL | 1,008 ng/dL |
| Tlando (n = 95) | Serum | 476 ng/dL | 979 ng/dL (morning), 989 ng/dL (evening) |
| Kyzatrex (n = 127–130) | NaF-EDTA plasma | 393 ng/dL | 852 ng/dL |
The sample type matters. Blood esterases keep converting TU to testosterone in the tube after it is drawn, which inflates the result. Tubes containing sodium fluoride (NaF), an esterase inhibitor, reduced this overestimate by 30–85% in a lab study (Ceponis et al., Andrology 2019). This is why the Jatenzo trial reported serum-equivalent Cavg as about 489 ng/dL, higher than the plasma value (Swerdloff et al., JCEM 2020). The labels’ titration charts are based on ordinary serum testosterone.
Food is required
Because absorption depends on dietary fat, every label says to take the capsules with food. The size of the effect varies by formulation:
| Product | Food study result |
|---|---|
| Andriol Testocaps, 80 mg (16 postmenopausal women) | Peak testosterone 0.67 ng/mL fasting vs 10.7 ng/mL after breakfast; AUC 5.37 vs 56.4 ng·h/mL |
| Andriol Testocaps, 80 mg (24 postmenopausal women) | Testosterone AUC 30.7, 43.5, 146 and 154 nmol·h/L with meals of 0.6, 5, 19 and 44 g fat |
| Jatenzo | 15 g fat breakfast gave 25% lower exposure than 30 g; 30 g, 45 g and high-fat meals were comparable |
| Tlando | Fasting gave ≈ 65% lower Cmax and 38% lower AUC than a high-fat meal; low, moderate and high fat were comparable |
| Kyzatrex | Breakfasts with 16%, 33% and 45% fat raised AUC by 37%, 87% and 94% compared with fasting |
Sources: Bagchus et al., Pharmacotherapy 2003; Schnabel et al., Clin Endocrinol 2007; US labels.
The Andriol studies were done in postmenopausal women so that their own testosterone would not mask the drug’s. The practical point from the second study: about 19 g of fat per meal was enough, and more fat added little.
More DHT than other routes
Because some TU is converted to DHTU in the gut wall, oral TU tends to raise DHT more than other forms of testosterone. With Tlando, mean 24-hour DHT was 108 ng/dL, and circulating levels of the esters themselves were high: TU 11,100 ng/dL and DHTU 4,700 ng/dL (Tlando label).
In a crossover study in 11 young men with medically induced hypogonadism, oral TU raised both testosterone and DHT into and above their normal ranges. Adding finasteride 0.5 or 1 mg twice daily did not lower DHT, unlike with other oral testosterone formulations. The authors suggested the lymphatic route explains the difference (Roth et al., Int J Androl 2011).
Approved medical use
All three US labels cover testosterone replacement in adult males with a deficiency or absence of their own testosterone due to:
- primary hypogonadism (testicular failure), congenital or acquired;
- hypogonadotropic hypogonadism (pituitary or hypothalamic failure), congenital or acquired.
The diagnosis must be confirmed with morning testosterone measured below the normal range on at least two separate days. The labels state that safety and efficacy have not been established in men with “age-related hypogonadism” or in males under 18.
Each product has its own monitoring rule:
| Product | When to check serum testosterone | Target or action |
|---|---|---|
| Jatenzo | 6 h after the morning dose, at least 7 days after starting or changing dose | 425–970 ng/dL: no change; adjust up or down outside that range |
| Tlando | 8–9 h after the morning dose, 3–4 weeks after starting | 300–1,080 ng/dL: continue; below or above: stop |
| Kyzatrex | 3–5 h after the morning dose, 7 days after starting or changing dose | 460–971 ng/dL: no change; adjust up or down outside that range |
The European Testocaps label covered testosterone replacement for confirmed male hypogonadism and osteoporosis due to androgen deficiency in men (Restandol Testocaps SmPC). In Ireland the licence dates to 1978, and the HPRA lists it as withdrawn on December 31, 2020.
What the research shows
Restoring testosterone in hypogonadal men
FDA approval of testosterone products rests on a pharmacokinetic endpoint: the share of men whose 24-hour average testosterone ends up in the normal range. The pivotal trials, all industry-funded, report:
| Trial | Product | Design and n | Duration | Men with Cavg in normal range |
|---|---|---|---|---|
| Swerdloff et al., JCEM 2020 | Jatenzo | Randomized, open-label; 166 oral TU vs 56 topical gel | 3–4 months | 87% (same as gel) |
| DelConte et al., Andrology 2022 | Tlando, fixed 225 mg twice daily | Single-arm; 95 men | 24 days | 80% (95% CI 72–88%) |
| Miner et al., Andrology 2025 | Tlando, titrated regimen | Randomized 2:1 vs AndroGel 1.62%; 315 men | Titrated at weeks 4 and 8 | 87.4% |
| Bernstein and Dhingra, Ther Adv Urol 2024 | Kyzatrex | Single-arm; 155 men | 6 months (efficacy at day 90) | 87.8% |
In the Jatenzo trial, sexual desire, enjoyment, activity, erection measures and mood improved from baseline in both arms, with no difference between oral TU and the gel. A 12-month extension of a separate one-year Jatenzo trial kept 69 men on therapy for 24 months. Mean serum testosterone over the two years was 617 ± 427 ng/dL, and scores for sexual function stayed improved (Honig et al., J Sex Med 2022).
These trials were open-label or uncontrolled for symptoms, and none was designed to measure muscle, bone or long-term clinical outcomes.
Older men with borderline-low testosterone (Andriol)
The older formulation was tested in placebo-controlled trials in older men, a group outside the current US indication:
- Body composition. 76 healthy men aged 60 or older with low-normal testosterone took 80 mg twice daily or placebo for 1 year. Lean mass rose and fat mass fell compared with placebo, but muscle strength did not change (Wittert et al., J Gerontol 2003).
- Symptoms. 322 men aged 50 or older with symptoms and low calculated free testosterone took 80, 160 or 240 mg/day or placebo for 12 months. The total Aging Males’ Symptoms score at 6 months did not improve more than with placebo. Only the sexual-symptom subscore improved, and only at 160 mg/day (Legros et al., Eur J Endocrinol 2009).
Long-term use of the old formulation
A 10-year follow-up of 33 men on Andriol found no change in liver function tests (Gooren, J Androl 1994). It also showed the old product’s limits. Measured 7–9 h after a dose, testosterone averaged 5.4–6.5 nmol/L, below the normal range of 8–24, while DHT averaged 3.2–3.5 nmol/L, above its normal range of 0.8–2.5.
Side effects and risks
Blood pressure
All three US labels state that the capsules can raise blood pressure, which can increase cardiovascular risk over time. Each was tested with 24-hour ambulatory blood pressure monitoring (ABPM):
| Product | Study | Change in 24-h systolic BP (95% CI) | Change in 24-h diastolic BP (95% CI) | Systolic change in men with hypertension |
|---|---|---|---|---|
| Jatenzo | 4 months, n = 135 | +4.9 mm Hg (3.5–6.4) | +2.5 mm Hg (1.5–3.6) | +5.4 mm Hg (on treatment, n = 67) |
| Tlando | About 16 weeks, n = 123 | +4.3 mm Hg (2.1–6.5) | +1.4 mm Hg (0.5–2.3) | +4.8 mm Hg (history of hypertension, n = 60) |
| Kyzatrex | 4 months, n = 151 | +1.7 mm Hg (0.3–3.1) | +0.6 mm Hg (−0.3 to 1.6) | +3.4 mm Hg (on treatment, n = 49) |
Sources: US labels. These were separate, uncontrolled studies in different populations, so the products cannot be ranked from this table.
On Jatenzo, 7.2% of men started or increased blood pressure medicine during the study, and the label notes that average blood pressure had not plateaued by the end. In the published Tlando ABPM study, men in the top quarter of hematocrit rise (6–14 percentage points) had the largest systolic increase, a mean of 8.3 mm Hg (White et al., J Cardiovasc Pharmacol Ther 2021).
Until 2025, this risk was a boxed warning on all three labels. The labels’ “Recent Major Changes” sections show that the boxed warning was removed in 2025. Blood pressure moved to Warnings and Precautions, together with results from TRAVERSE, a cardiovascular outcomes trial of testosterone gel (not oral TU). TRAVERSE found major cardiovascular events in 7.0% on gel vs 7.3% on placebo. The labels still say the capsules are not recommended in men with uncontrolled hypertension.
Hematocrit and lipids
| Measure | Result |
|---|---|
| Hematocrit vs placebo (network meta-analysis, 29 trials, 3,393 men) | +4.3% (95% CI 0.7–8.0) for oral TU; +4.0% for IM enanthate/cypionate; +3.0% for gel |
| Hematocrit (Jatenzo trial) | +6.0% relative rise vs +4.7% on gel; 3% moved from normal to above normal |
| HDL cholesterol (Jatenzo trial) | −13.9% vs −3.4% on gel |
| LDL cholesterol (Jatenzo trial) | +6.0% vs −2.1% on gel |
| Triglycerides (Jatenzo trial) | +13.0% vs +8.1% on gel |
| HDL cholesterol (Jatenzo, 2 years) | −9.8 mg/dL; hematocrit stayed under 48% |
| SHBG (Jatenzo trial) | −36%, which raises free testosterone |
Sources: Nackeeran et al., J Urol 2022; Swerdloff et al., JCEM 2020; Honig et al., J Sex Med 2022.
The confidence interval for oral TU in the meta-analysis is wide because few placebo-controlled trials used it. The labels advise checking hematocrit before starting and about every 3 months, and stopping the drug if it becomes elevated.
Liver
“Oral testosterone is toxic to the liver.” This is true of 17α-alkylated androgens such as methyltestosterone, which the labels link to peliosis hepatis, liver tumors and cholestatic jaundice. Testosterone undecanoate is not 17α-alkylated. The Jatenzo and Kyzatrex labels state that their products are not known to cause these effects, the Jatenzo trial found no clinically significant changes in liver enzymes, and the 10-year Andriol cohort found no change in liver function. The labels still advise stopping the drug and checking if jaundice or other signs of liver problems appear.
Other label-listed effects
In the 4-month Jatenzo trial (n = 166), the adverse reactions seen in at least 2% of men were (Jatenzo label):
| Adverse reaction | Rate |
|---|---|
| Headache | 4.8% |
| Hematocrit increased | 4.8% |
| Hypertension | 3.6% |
| HDL decreased | 3.0% |
| Nausea | 2.4% |
Across all 569 men in the Jatenzo phase 2 and 3 trials, the label also lists diarrhea, dyspepsia, belching and peripheral edema at over 2%. Gastrointestinal complaints fit the oily capsule fill; the European label notes that high doses can cause them for that reason. Two of the 166 men reported new or worsening depression, and the label carries a warning about depression and suicidal ideation.
Class warnings shared with other testosterone products include:
- Venous thromboembolism. Deep vein thrombosis and pulmonary embolism have been reported with testosterone products.
- Prostate. Possible worsening of benign prostatic hyperplasia and a potential risk of prostate cancer. In the Jatenzo trial, mean PSA rose by 0.2 ng/mL.
- Fertility. Exogenous testosterone suppresses LH and FSH and can reduce sperm production, possibly to zero. The Jatenzo label warns that the effect on fertility may be irreversible.
- Edema, gynecomastia and sleep apnea, especially in men with heart, kidney or liver disease, or with obesity or lung disease for sleep apnea.
In dogs given Jatenzo for 3 and 9 months, the label reports shrinkage of the adrenal glands and lower cortisol. This is animal data, and the label states that its clinical significance is unknown.
Interactions
The US labels list these interactions:
- Insulin and diabetes medicines. Androgens can lower blood glucose, so doses may need reducing.
- Warfarin. Androgens can change its effect; INR should be checked more often, especially when starting or stopping testosterone.
- Corticosteroids. Combined use can increase fluid retention.
- Drugs that raise blood pressure, including some over-the-counter cold and pain medicines.
At a 237 mg dose, Jatenzo had no clinically meaningful effect on midazolam, digoxin or rosuvastatin levels. The European label adds that enzyme-inducing drugs such as barbiturates may lower testosterone levels.
Who should not use it
The US labels contraindicate oral TU in:
- men with breast cancer or known or suspected prostate cancer;
- pregnant women, because testosterone can virilize a female fetus;
- anyone with hypersensitivity to the product or its ingredients.
The capsules are not indicated for women. The European Testocaps label also listed hypercalcemia, nephrotic syndrome, ischemic heart disease, untreated heart failure, and peanut or soya allergy (the capsules may contain traces of soya lecithin).
Legal status and use outside medicine
In the US, testosterone and its esters are Schedule III anabolic steroids under 21 CFR 1308.13, and all three capsule brands carry the CIII designation. Andriol was never approved by the FDA; the only oral TU products listed in Drugs@FDA are Jatenzo, Tlando and Kyzatrex.
The WADA 2026 Prohibited List prohibits testosterone and its esters at all times, in and out of competition, under S1.1 anabolic androgenic steroids. The US labels note that testosterone has been abused, usually at doses far above the approved range and alongside other anabolic steroids.
Key takeaways
- Testosterone that survives being swallowed. The undecanoate ester lets part of each dose enter the blood through the gut’s lymphatic system, partly bypassing the liver. Bioavailability is still only about 7% for Andriol.
- Food and twice-daily dosing are essential. TU’s half-life is about 2 hours, and taking it without fat can cut testosterone exposure by more than half.
- Brands are not interchangeable. Jatenzo, Tlando and Kyzatrex use different formulations, doses and lab-timing rules, and the labels say they cannot be substituted mg for mg.
- Blood pressure is the distinctive risk. Ambulatory systolic pressure rose by about 2–5 mm Hg in the US trials, more in men already treated for hypertension.
- No 17α-alkyl liver toxicity. Liver enzymes did not change meaningfully in trials, but hematocrit, HDL, PSA and fertility effects are the same as with other testosterone forms.
- Normal levels, limited outcome data. About 80–88% of men reached normal average testosterone in pivotal trials, but those trials were short and did not test long-term cardiovascular or bone outcomes.
Sources
- Tolmar Inc. Jatenzo (testosterone undecanoate) capsules, for oral use, prescribing information. DailyMed; Drugs@FDA, NDA 206089.
- Verity Pharmaceuticals Inc. Tlando (testosterone undecanoate) capsules, for oral use, prescribing information. DailyMed; Drugs@FDA, NDA 208088.
- Marius Pharmaceuticals. Kyzatrex (testosterone undecanoate) capsules, for oral use, prescribing information. DailyMed; Drugs@FDA, NDA 213953.
- Merck Sharp & Dohme Ireland. Restandol Testocaps 40 mg soft capsules, Summary of Product Characteristics, February 2020. HPRA; licence status: HPRA.
- Köhn FM, Schill WB. A new oral testosterone undecanoate formulation. World J Urol. 2003;21(5):311–315. PubMed.
- Horst HJ, Höltje WJ, Dennis M, et al. Lymphatic absorption and metabolism of orally administered testosterone undecanoate in man. Klin Wochenschr. 1976;54(18):875–879. PubMed.
- Bagchus WM, Hust R, Maris F, et al. Important effect of food on the bioavailability of oral testosterone undecanoate. Pharmacotherapy. 2003;23(3):319–325. PubMed.
- Schnabel PG, Bagchus W, Lass H, et al. The effect of food composition on serum testosterone levels after oral administration of Andriol Testocaps. Clin Endocrinol (Oxf). 2007;66(4):579–585. PubMed.
- Ceponis J, Swerdloff R, Leung A, et al. Accurate measurement of androgen after androgen esters: problems created by ex vivo esterase effects and LC-MS/MS interference. Andrology. 2019;7(1):42–52. PubMed.
- Roth MY, Dudley RE, Hull L, et al. Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5α-reductase by finasteride. Int J Androl. 2011;34(6 Pt 1):541–547. PubMed.
- Swerdloff RS, Wang C, White WB, et al. A new oral testosterone undecanoate formulation restores testosterone to normal concentrations in hypogonadal men. J Clin Endocrinol Metab. 2020;105(8):2515–2531. PubMed.
- Honig S, Gittelman M, Kaminetsky J, et al. Two-year analysis of a new oral testosterone undecanoate (TU) formulation in hypogonadal men: efficacy, impact on psychosexual function, and safety. J Sex Med. 2022;19(12):1750–1758. PubMed.
- DelConte A, Papangkorn K, Kim K, et al. A new oral testosterone (TLANDO) treatment regimen without dose titration requirement for male hypogonadism. Andrology. 2022;10(4):669–676. PubMed.
- Miner M, Wang C, Kaminetsky J, et al. Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism. Andrology. 2025;13(4):882–893. PubMed.
- Bernstein JS, Dhingra OP. A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product. Ther Adv Urol. 2024;16:17562872241241864. PubMed.
- White WB, Dobs A, Carson C, et al. Effects of a novel oral testosterone undecanoate on ambulatory blood pressure in hypogonadal men. J Cardiovasc Pharmacol Ther. 2021;26(6):630–637. PubMed.
- Wittert GA, Chapman IM, Haren MT, et al. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci. 2003;58(7):618–625. PubMed.
- Legros JJ, Meuleman EJ, Elbers JM, et al. Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. Eur J Endocrinol. 2009;160(5):821–831. PubMed.
- Gooren LJ. A ten-year safety study of the oral androgen testosterone undecanoate. J Androl. 1994;15(3):212–215. PubMed.
- 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.
- US Code of Federal Regulations. 21 CFR 1308.13, Schedule III. eCFR.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.