ALPHA

Head to head

Subcutaneous vs Intramuscular Testosterone

One product in the United States is FDA-labelled for weekly subcutaneous testosterone. Every oil vial is labelled intramuscular only. Injecting a vial under the skin is common, published, and not on any label — and this page says which is which in every row.

Reviewed

The short answer

Start with the fact that decides how to read everything else: exactly one testosterone product in the United States is labelled for subcutaneous injection, and it is not a vial. XYOSTED is a fixed-dose autoinjector, and its label is unusually blunt about the route — "XYOSTED is for subcutaneous injection in the abdominal region only. Avoid intramuscular or intravascular injection." An openFDA census of every testosterone label record returns 44 routed intramuscular and 2 routed subcutaneous, and one of those two is Testopel, an implanted pellet rather than an injection.

Drawing testosterone cypionate from a vial and injecting it subcutaneously is common practice, it has published support, and it is not described on any FDA label. DEPO-Testosterone's own dosage section says "DEPO-Testosterone Injection is for intramuscular use only… Intramuscular injections should be given deep in the gluteal muscle", and the carton prints "For intramuscular use only". That does not mean the practice is wrong; it means no regulator has evaluated the vial by that route, and nothing on this page supplies a subcutaneous dose, volume, needle or site for one.

The safety claim most repeated about XYOSTED is out of date. It carried a boxed warning about blood pressure increases and FDA removed it — the label's own Recent Major Changes table reads "Boxed Warnings, Blood Pressure Increases — Removed 03/2025", and there is no boxed warning anywhere in the current document. What was not removed is the blood pressure content itself: section 5.4 still states that XYOSTED raised systolic/diastolic pressure by an average of 3.9/1.5 mm Hg over 12 weeks and that it is "Not recommended for use in men with uncontrolled hypertension." The warning moved down the page; it did not go away.

The real asymmetry is in what each label knows about itself. XYOSTED publishes week-12 pharmacokinetics — mean C-avg 553 ng/dL, C-max 790, C-min 436 — from a named 52-week trial. Neither oil vial label publishes a single serum testosterone concentration; DEPO-Testosterone has no clinical studies section at all, because it is a pre-modern ANDA whose entire pharmacokinetics section is five paragraphs and one number, "approximately eight days".

2 of 15 dimensions are materially the same. They are marked below rather than dressed up as differences.

Subcutaneous

XYOSTED (testosterone enanthate autoinjector)

Into the fat under the skin. One FDA-labelled testosterone injection uses this route: XYOSTED, NDA 209863, 75 mg weekly into the abdomen from a fixed 0.5 mL autoinjector.

Dosing protocol →

Intramuscular

Depo-Testosterone · testosterone enanthate injection, USP · Aveed

Deep into muscle. Every testosterone oil vial sold in the US is labelled this way, most of them "deep in the gluteal muscle", at 50 to 400 mg every two to four weeks.

Dosing protocol →

Side by side

Every row carries how well supported it is. A claim that only reflects common practice is labelled as such rather than presented as fact.

DimensionSubcutaneousIntramuscularBasis
Products labelled for this routeOne injection — XYOSTED, NDA 20986344 label recordslabelopenFDA route census of every testosterone label record, data refresh 2026-09-18: 44 INTRAMUSCULAR, 2 SUBCUTANEOUS. The two subcutaneous records are XYOSTED and TESTOPEL — and Testopel is an implanted pellet, not an injection, so XYOSTED stands alone as the labelled subcutaneous testosterone injection.
What the label says about the other route"Avoid intramuscular or intravascular injection""For intramuscular use only"labelEach label forbids the other route in its own words. XYOSTED section 2.3: "XYOSTED is for subcutaneous injection in the abdominal region only. Avoid intramuscular or intravascular injection." DEPO-Testosterone: "DEPO-Testosterone Injection is for intramuscular use only. It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle." The generic enanthate vial prints "For Intramuscular Use ONLY" on the carton.
Injecting the oil vials the other wayWidespread practice, on no labelThe labelled route for every vialpracticeThe reason most people are reading this page, and the honest answer is that subcutaneous injection of testosterone cypionate or enanthate drawn from a vial is ordinary clinical practice with published support and zero labelling. No FDA label describes it, states a dose for it, specifies a site or needle for it, or evaluates it. That makes it unlabelled use — lawful for a prescriber to direct, and outside anything a regulator has reviewed. This page prints no subcutaneous figure for any vial.
Labelled dose and interval75 mg once weekly, ±25 mg on trough50 to 400 mg every two to four weekslabelXYOSTED: "The starting dose of XYOSTED is 75 mg, administered subcutaneously in the abdominal region once a week", adjusted by 25 mg against a 350–650 ng/dL trough measured 7 days after a dose. DEPO-Testosterone: "For replacement in the hypogonadal male, 50 - 400 mg should be administered every two to four weeks." Weekly dosing of the vials is itself common practice rather than a labelled schedule.
Injection siteAbdomen only, left or right sideDeep in the gluteal musclelabelXYOSTED's Instructions for Use is prescriptive: "Only use the left or right side of the abdomen (belly) for injection sites", squeeze to raise the skin, autoinjector at 90 degrees. No thigh, no arm. The enanthate vial says "Care should be taken to slowly inject the preparation deeply into the gluteal muscle, being sure to follow the usual precautions for intramuscular administration, such as the avoidance of intravascular injection."
What you inject withA pressure-assisted autoinjector, fixed 0.5 mLYour own syringe and needle, volume you drawlabelA device difference that is easy to underrate. XYOSTED is "a single-dose syringe pre-assembled in an autoinjector" at 50, 75 or 100 mg in 0.5 mL — three strengths and no dose in between. A vial plus syringe gives any dose the concentration allows and puts the measurement on the person doing it. Neither label states a needle gauge, so none is stated here.
Vehicle and preservativeSesame oil, preservative-free, single doseCottonseed or sesame oil, preserved, multi-doselabelXYOSTED is "sterile, preservative-free, and nonpyrogenic… testosterone enanthate in sesame oil". DEPO-Testosterone 100 mg/mL is cottonseed oil 736 mg with benzyl benzoate 0.1 mL and benzyl alcohol 9.45 mg per mL as preservative; the generic enanthate vial is sesame oil with 5 mg chlorobutanol. The preservative is what makes a vial re-enterable — and no label states a subcutaneous tolerance for any of them, so none is given.
Boxed warningsameNone — removed 03/2025None on the oil vialslabelBoth currently have none, and one of them used to. XYOSTED's Recent Major Changes table reads "Boxed Warnings, Blood Pressure Increases — Removed 03/2025" and "Warnings and Precautions, Cardiovascular Risk (5.4) — Removed 03/2025"; the document contains no boxed warning. Most secondary sources have not caught up and still describe one.
Blood pressure content that remains3.9/1.5 mm Hg at 12 weeks; avoid in uncontrolled hypertensionNot quantified on either vial labellabelThe removal of the box did not remove the finding. XYOSTED section 5.4, dated 03/2025: "XYOSTED can increase blood pressure. Ambulatory blood pressure monitoring (ABPM) demonstrated XYOSTED increased systolic/diastolic BP by an average of 3.9/1.5 mm Hg from baseline after 12 weeks of treatment", with "Not recommended for use in men with uncontrolled hypertension" in the Highlights. The oil labels carry no blood pressure figure at all — which is absence of measurement, not evidence of absence.
Published pharmacokineticsC-avg 553 (127), C-max 790 (215), C-min 436 (109) ng/dLNo serum concentration publishedlabelXYOSTED Table 3, arithmetic mean (SD) at week 12, N=137, and section 14 adds that 90% of 150 men were within 300–1100 ng/dL with no patient above a C-max of 1500. Neither oil label states a single concentration: the cypionate label's whole pharmacokinetics section offers one number, "The half-life of testosterone cypionate when injected intramuscularly is approximately eight days", and has no clinical studies section at all.
Injection reaction as reported12.7% of 283 patients over up to a year"Inflammation and pain at the site of intramuscular injection"labelDifferent levels of detail rather than different rates. XYOSTED counts them: "Injection site reactions, including injection site bruising, injection site hemorrhage, injection site erythema and injection site induration were reported in 36 of the 283 patients… No patients discontinued XYOSTED because of injection site reactions." The vial labels list the reaction without a frequency, because these are pre-PLR labels that do not report incidence.
The cough reactionCough in 2.7%, cause not attributed to routePost-marketing reports of coughing fits immediately after injectionlabelOn the enanthate vial label, verbatim: "There have been rare post-marketing reports of transient reactions involving urge to cough, coughing fits, and respiratory distress immediately after the injection of testosterone enanthate, an oil-based depot preparation." It sits in the intramuscular administration paragraph, next to the instruction to avoid intravascular injection. XYOSTED lists cough at 2.7% in its adverse reaction table without linking it to the injection itself.
Head-to-head in hypogonadal menLower post-therapy oestradiol and haematocritComparator armliterature234 hypogonadal men on IM testosterone cypionate 100 mg weekly or the subcutaneous enanthate autoinjector 100 mg weekly for 12 weeks. Treatment modality "was not found to be associated with TT levels (p=0.057)"; the autoinjector was independently associated with lower oestradiol and haematocrit. Read what changed between arms: the ester, the route AND the device all differ, so this cannot isolate the route. Retrospective, not randomised.
Evidence for subcutaneous oil from a vialTwo cohorts, 63 and 11 patients, not in menThe labelled route; no comparison neededliteratureThe papers routinely cited for subcutaneous cypionate were done in female-to-male transgender patients at one clinic, not in hypogonadal men. The follow-up study says so itself: "It is anticipated that these results can be extended to hypogonadal men." That sentence is an expectation the authors wrote down, and it is quoted here rather than converted into a finding.
Monitoring either waysameHaematocrit about every 3 monthsHaemoglobin and haematocrit periodicallylabelThe same surveillance for the same reason. XYOSTED: "Monitor hematocrit approximately every 3 months to detect increased red blood cell mass and polycythemia." DEPO-Testosterone: "Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration." Route does not change what needs watching.
label
Stated on the FDA label
guideline
Clinical practice guideline
literature
Published literature
practice
Common practice, not documented

Which one

Choose Subcutaneous if

  • You want the route a regulator has actually reviewed, with a product approved for it. That is the whole case for XYOSTED and for most men it is enough.
  • Weekly dosing at a documented trough matters to you. XYOSTED is titrated against a 350–650 ng/dL trough measured seven days after a dose, and its label publishes what the resulting week looks like.
  • A gluteal injection is the thing standing between you and treatment. An abdominal autoinjector removes the needle, the draw, the angle and the site decision.
  • You want the lower oestradiol and haematocrit signal from the one comparison in hypogonadal men — while accepting that the study changed the ester and the device as well as the route.

Choose Intramuscular if

  • You need a dose the autoinjector does not offer. XYOSTED comes in 50, 75 and 100 mg and nothing in between; a vial gives whatever the concentration allows.
  • Cost matters. A multi-dose vial and a syringe is the cheapest way testosterone is supplied in the United States, and an autoinjector is not.
  • Every two weeks suits you better than every week. That is the labelled interval on the vials and there is no two-weekly subcutaneous product.
  • You are already stable on an intramuscular regimen. Nothing on this page is a reason to disturb a regimen that is working.

What this page will not do is tell you to inject a vial subcutaneously or how to. It is common, it is published, prescribers direct it every day, and no FDA label describes it — so there is no labelled dose, site, volume or needle for it, and inventing one would be exactly the failure this page type exists to prevent. If your prescriber has told you to inject your cypionate subcutaneously, that is their clinical judgement and it is worth asking what it is based on. And if you read anywhere that XYOSTED carries a boxed warning, check the date: FDA removed it in March 2025, while leaving the blood pressure finding in place one section further down.

Frequently asked questions

Can I inject testosterone cypionate subcutaneously?
Many men do and no FDA label describes it. DEPO-Testosterone's dosage section says "DEPO-Testosterone Injection is for intramuscular use only. It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle", and "For intramuscular use only" is printed on the carton. Every testosterone oil vial in the United States says some version of that — an openFDA census returns 44 label records routed intramuscular and two routed subcutaneous, and the subcutaneous pair is XYOSTED, which is an autoinjector, and Testopel, which is an implanted pellet. So subcutaneous injection of a vial is unlabelled use: lawful for a prescriber to direct, supported by published cohorts, and not something FDA has evaluated. This page gives no subcutaneous dose, volume, site or needle for a vial, because no label states one.
Does XYOSTED still have a boxed warning?
No. The current label's Recent Major Changes table lists "Boxed Warnings, Blood Pressure Increases — Removed 03/2025" alongside "Warnings and Precautions, Cardiovascular Risk (5.4) — Removed 03/2025", and there is no boxed warning element anywhere in the document. A great many secondary sources — comparison articles, clinic pages, older summaries — still describe one, and they have not been updated. The important half of the answer is what stayed: section 5.4, dated 03/2025, still says "XYOSTED can increase blood pressure. Ambulatory blood pressure monitoring (ABPM) demonstrated XYOSTED increased systolic/diastolic BP by an average of 3.9/1.5 mm Hg from baseline after 12 weeks of treatment in clinical trials", and the Highlights still carry "Not recommended for use in men with uncontrolled hypertension." The warning was demoted from the box, not deleted from the label.
Is subcutaneous injection less likely to spike my levels?
The only label that publishes the numbers is XYOSTED's, and they are steady: at week 12 in 137 men on 50, 75 or 100 mg weekly, mean C-avg was 553 ng/dL, C-max 790 and C-min 436, and section 14 records that no patient exceeded a C-max of 1500 ng/dL at week 12. What cannot be done is to compare that with the oil vials, because neither vial label publishes a single serum concentration — DEPO-Testosterone's entire pharmacokinetics section offers one figure, an eight-day half-life, and has no clinical studies section at all. Part of the difference people attribute to the route is really the interval: XYOSTED is weekly and the vials are labelled every two to four weeks. A trial in 234 hypogonadal men found the modality "was not found to be associated with TT levels (p=0.057)" once adjusted.
Where does the evidence for subcutaneous testosterone actually come from?
Two places, and it is worth knowing which. The first is XYOSTED's own programme: a 52-week open-label study (NCT02159469) in 150 adult hypogonadal men, in which "One hundred and thirty five (90%) of the 150 hypogonadal men who received XYOSTED had a serum total testosterone concentration Cavg(0-168h) within the normal range (300 to 1100 ng/dL) at Week 12." The second is the literature people cite for injecting vials subcutaneously, and that is thinner than it looks: the two most-quoted papers studied 63 and 11 female-to-male transgender patients at one academic clinic, not hypogonadal men, and the second states its own limitation plainly — "It is anticipated that these results can be extended to hypogonadal men."
Which one hurts less?
Neither label answers that question and this page will not invent an answer to it. What the labels do report is different in kind rather than in degree. XYOSTED counts its injection reactions: 36 of 283 patients, 12.7%, over up to a year, with "No patients discontinued XYOSTED because of injection site reactions." The oil vial labels list "Inflammation and pain at the site of intramuscular injection" with no frequency attached, because they are pre-modern labels that do not report incidence. The enanthate label also carries something the autoinjector label does not: "rare post-marketing reports of transient reactions involving urge to cough, coughing fits, and respiratory distress immediately after the injection", which sits directly beside its instruction to avoid intravascular injection.
Can I switch between the two routes at the same dose?
Not as arithmetic, and no label supports a conversion. XYOSTED and the oil vials are different esters, different vehicles, different intervals and different dose ranges: 75 mg weekly adjusted in 25 mg steps against a measured trough, versus 50 to 400 mg every two to four weeks with no trough target stated. XYOSTED also only exists at 50, 75 and 100 mg, so a dose from a vial frequently has no autoinjector equivalent. If you switch, the new product starts at its own labelled starting dose and is titrated on its own terms, and the trough measurement seven days after a dose is the thing that tells your prescriber where you have landed.

Sources

  1. [1]FDA label — XYOSTED (testosterone enanthate) injection, for subcutaneous use, Antares Pharma, Inc. (DailyMed SPL 8a3d204c-be26-49e0-8599-0ac12a272e81; approval block NDA 209863, marketing category NDA), fetched in full 2026-09-20. Source of "XYOSTED is for subcutaneous injection in the abdominal region only. Avoid intramuscular or intravascular injection."; of "The starting dose of XYOSTED is 75 mg, administered subcutaneously in the abdominal region once a week."; of the Recent Major Changes entries "Boxed Warnings, Blood Pressure Increases — Removed 03/2025" and "Warnings and Precautions, Cardiovascular Risk (5.4) — Removed 03/2025"; of section 5.4 "XYOSTED can increase blood pressure. Ambulatory blood pressure monitoring (ABPM) demonstrated XYOSTED increased systolic/diastolic BP by an average of 3.9/1.5 mm Hg from baseline after 12 weeks of treatment in clinical trials."; of the Table 3 week-12 pharmacokinetics; of "Injection site reactions… were reported in 36 of the 283 patients in the 2 clinical studies, representing 12.7%… No patients discontinued XYOSTED because of injection site reactions."; and of the Instructions for Use line "Only use the left or right side of the abdomen (belly) for injection sites." The document contains no boxed warning
  2. [2]FDA label — DEPO-TESTOSTERONE (testosterone cypionate) injection, USP, Pharmacia and Upjohn (DailyMed SPL cfbb53d4-b868-4a28-8436-f9112eb01c39; approval block ANDA 085635). Source of "DEPO-Testosterone Injection is for intramuscular use only.", "It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle.", the carton text "For intramuscular use only", "For replacement in the hypogonadal male, 50 - 400 mg should be administered every two to four weeks.", "The half-life of testosterone cypionate when injected intramuscularly is approximately eight days.", the per-mL composition (cottonseed oil 736 mg, benzyl benzoate 0.1 mL, benzyl alcohol 9.45 mg as preservative) and "Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically". This label has no clinical studies section and states no serum testosterone concentration
  3. [3]FDA label — TESTOSTERONE ENANTHATE INJECTION, USP (DailyMed SPL e89d6458-428c-4256-97a3-f1fa851293c1; approval block ANDA 091120). Source of "Each mL of sterile, colorless to pale yellow, solution provides 200 mg Testosterone Enanthate, USP in sesame oil with 5 mg chlorobutanol (chloral derivative) as a preservative."; of "Care should be taken to slowly inject the preparation deeply into the gluteal muscle, being sure to follow the usual precautions for intramuscular administration, such as the avoidance of intravascular injection."; of "There have been rare post-marketing reports of transient reactions involving urge to cough, coughing fits, and respiratory distress immediately after the injection of testosterone enanthate, an oil-based depot preparation"; and of the principal display panel "For Intramuscular Use ONLY"
  4. [4]openFDA drug label endpoint — route census across every testosterone label record, data refresh 2026-09-18. INTRAMUSCULAR 44, ORAL 33, TOPICAL 18, TRANSDERMAL 17, SUBLINGUAL 5, SUBCUTANEOUS 2, NASAL 1. A follow-up query restricted to the subcutaneous route returns exactly two products: XYOSTED (NDA 209863, Antares Pharma) and Testopel (ANDA 080911, Endo USA), the latter an implanted pellet rather than an injection
  5. [5]Choi EJ, Xu P, Barham D, El-Khatib FM, Yafi FA, Kavoussi PK. Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate. J Urol. 2022;207(3):677–683 (PMID 34694927). "A total of 234 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC 100 mg weekly or SCTE-AI 100 mg weekly." "After linear regression, type of TRT modality was not found to be associated with TT levels (p=0.057). SCTE-AI was independently associated with lower post-therapy E2 (p <0.001) and HCT (p <0.001)." Note that the comparison changes ester, route and device simultaneously
  6. [6]Spratt DI, Stewart II, Savage C, et al. Subcutaneous Injection of Testosterone Is an Effective and Preferred Alternative to Intramuscular Injection: Demonstration in Female-to-Male Transgender Patients. J Clin Endocrinol Metab. 2017;102(7):2349–2355 (PMID 28379417). "Sixty-three FTM transgender patients aged >18 years electing to receive subcutaneous (SC) T therapy for sex transition were included." "Serum T levels within the normal male range were achieved in all 63 patients with doses of 50 to 150 mg (median, 75/80 mg)." The population is named in the title and is not hypogonadal men
  7. [7]McFarland J, Craig W, Clarke NJ, Spratt DI. Serum Testosterone Concentrations Remain Stable Between Injections in Patients Receiving Subcutaneous Testosterone. J Endocr Soc. 2017;1(8):1095–1103 (PMID 29264562). "Eleven FTM transgender patients already receiving weekly SC testosterone cypionate with documented therapeutic levels prior to enrollment had free and total serum testosterone levels measured at eight different time points during a 1-week dosing interval." And the sentence this page quotes rather than paraphrases: "It is anticipated that these results can be extended to hypogonadal men."

Next steps

Other comparisons

Educational reference, not medical advice. Which medication suits you is a decision for your prescriber.