Short answer: Both routes can produce normal testosterone levels, but only one US product is labeled for subcutaneous (under-the-skin) use: Xyosted, a weekly enanthate autoinjector. Standard cypionate vials such as Depo-Testosterone are labeled "for intramuscular use only," so injecting them under the skin is off-label. In Xyosted's registration trial, 92.7% of men reached the target testosterone range at week 12 and more than 95% reported no injection pain. One retrospective study found weekly SC enanthate was linked to lower hematocrit and estradiol than weekly IM cypionate. There is no large randomized head-to-head trial.
Many men on TRT have moved from deep muscle shots to small, under-the-skin injections with insulin-style needles. It is easier and usually less painful. But "SC is better" has become an online rule of thumb that goes further than the evidence. This article sets out what the labels say, what the trials and comparison studies found, and what is still unknown. It does not give dosing advice.
| Product | Labeled route | Key label wording |
|---|---|---|
| Depo-Testosterone (testosterone cypionate) | Intramuscular | "for intramuscular use only"; injections "should be given deep in the gluteal muscle" |
| Xyosted (testosterone enanthate autoinjector) | Subcutaneous | "for subcutaneous injection in the abdominal region only. Avoid intramuscular or intravascular injection." |
So the choice is not only practical. Using a vial labeled for intramuscular use as a subcutaneous shot is off-label. That is legal for a prescriber to direct, and common, but it means the label's absorption and safety data were not collected that way. The Depo-Testosterone label, for example, gives a half-life of about eight days "when injected intramuscularly."
Xyosted's approval rests on two open-label studies in men with low testosterone.
These are single-arm studies. They show the autoinjector works and is well tolerated. They do not compare it with intramuscular shots.
The most direct comparison we found is a retrospective study of 234 men treated with either intramuscular testosterone cypionate 100 mg weekly or the subcutaneous enanthate autoinjector 100 mg weekly (Choi 2022). After 12 weeks:
Two limits matter. It was not randomized, so the men in each group may have differed in ways the analysis did not capture. And it compared two different products (cypionate by IM vs an enanthate autoinjector by SC), not the same vial given two ways.
Evidence for injecting ordinary cypionate under the skin is smaller still. A study of 11 transgender men already on weekly subcutaneous testosterone cypionate measured levels at eight time points over one week (McFarland 2017). Mean total testosterone between injections was 627 ± 206 ng/dL and stayed within the normal range, with no adverse effects. The authors expected the results to extend to hypogonadal men, but that was not tested.
Pain is the main reason people switch. The Xyosted data are strong on this point (more than 95% no pain; one mild report in 965 injections). The Depo-Testosterone label lists "inflammation and pain at the site of intramuscular injection" among its side effects. Subcutaneous injections bring their own site issues; the Xyosted label lists injection-site bruising as a common reaction. Rotating sites helps either way; see our site rotation guide.
The Endocrine Society guideline says that for injectable testosterone enanthate or cypionate, clinicians should "measure serum T concentrations midway between injections," and adjust the dose or frequency if the mid-interval level is above 600 ng/dL or below 350 ng/dL. Xyosted's trials used a different anchor: doses were adjusted on the pre-dose (trough) level, with a target of 350 to 650 ng/dL in the 26-week study. If you change route, ask your prescriber which timing they want, and keep it the same before and after the switch so the numbers can be compared. Our steady-state guide explains why you should also wait several weeks after any change before testing.
A route change is a protocol change. The cleanest way to see its effect is to keep everything else the same and compare labs before and after at the same point in your injection cycle. Useful things to log:
Dose Track records route and injection site with each dose and lets you add lab results to the same timeline, so a before-and-after comparison is easy to show your prescriber. For the lab side, see hematocrit on TRT and estradiol on TRT.
Questions about the app? See the help center or join the Dose Track community.
Every number in this article comes from one of these sources, checked on October 22, 2026. This article is for education. It is not medical or legal advice, and nothing here is a dose recommendation.