Testosterone injections: what the evidence actually shows
Testosterone injections do not hold a flat level between doses. Dobs 1999 in the Journal of Clinical Endocrinology and Metabolism, a 24-week randomized trial in 66 hypogonadal men, found intramuscular enanthate given every 2 weeks produced supraphysiological levels for several days after each injection, with mean morning levels in the normal range in 19 to 84 percent of those patients.
Key takeaways
- Dobs 1999 in the Journal of Clinical Endocrinology and Metabolism found two-weekly intramuscular enanthate suppressed luteinizing hormone into the subnormal range in 31 percent of patients, against 0 percent on a patch.
- Choi 2021 in The Journal of Urology, comparing 234 men over 12 weeks, found the route was not associated with total testosterone after regression (p = 0.057), but subcutaneous use was independently associated with lower estradiol and lower hematocrit (both p less than 0.001).
- No randomized trial compares injection frequencies of the same short-acting ester.
- Hajjar 1997 in the Journal of Clinical Endocrinology and Metabolism found 11 of 45 men (24 percent) on two-weekly enanthate or cypionate for 2 years developed polycythemia requiring phlebotomy or temporary withholding.
- Liu 2025 in Blood Advances, reviewing 45 studies, reported erythrocytosis rates of up to 66.7 percent and thromboembolic events in up to 2.7 percent of men on testosterone therapy.
- Only two injectable testosterone products were marketed in Canada at the Health Canada Drug Product Database check of 14 September 2026, and two brand injectables were cancelled in 2025.
Who does this evidence apply to?
All of it applies to men with confirmed low testosterone. Health Canada’s product monograph for oral testosterone undecanoate, authorized 12 December 2025, requires deficiency to be clearly demonstrated by clinical features and confirmed by two separate validated biochemical assays of morning testosterone. What testing your own case needs is a decision for your doctor or nurse practitioner.
None of it applies to men whose testosterone is normal. The same monograph states the product should not be used for non-specific symptoms suggestive of hypogonadism if deficiency has not been demonstrated. For the diagnostic steps, see how low testosterone is diagnosed in Canada.
What do testosterone injections look like between doses?
They rise above the normal range and then fall through it. Dobs 1999 in the Journal of Clinical Endocrinology and Metabolism ran a 24-week randomized parallel-group trial in 66 hypogonadal men, comparing a permeation-enhanced patch against 200 mg of enanthate intramuscularly every 2 weeks.
The injection arm, in the authors’ words, produced supraphysiological levels of testosterone, bioavailable testosterone and estradiol, though not dihydrotestosterone, for several days after each injection. Mean morning sex hormone levels were within the normal range in 77 to 100 percent of patch patients versus 19 to 84 percent of injection patients, and luteinizing hormone was suppressed into the subnormal range in 31 percent of injection patients versus 0 percent on the patch.
That is the measured basis for the peak and trough description. The comparator, a patch, is no longer sold in Canada, the United States, the United Kingdom or Australia, so it documents the injection curve rather than a live choice. What the attached ester does to that curve is covered in testosterone esters explained.
Is subcutaneous better than intramuscular?
The one direct comparison found no significant difference in testosterone level, but differences in two secondary markers. Choi 2021 in The Journal of Urology studied 234 hypogonadal men given 100 mg weekly, either intramuscularly as cypionate or subcutaneously as enanthate, over 12 weeks.
Trough total testosterone rose in both groups, from 313.6 to 536.4 ng/dL with intramuscular cypionate and from 246.6 to 552.8 ng/dL with subcutaneous enanthate, both p less than 0.001. After linear regression, modality was not associated with total testosterone level (p = 0.057). Subcutaneous administration was independently associated with lower post-therapy estradiol and lower hematocrit (both p less than 0.001), and neither modality raised prostate specific antigen significantly (p = 0.965).
Two caveats decide the weight this carries. The study was not randomized, and route and ester change together between the arms, so no part of the result can be assigned to the route alone. It is still the best available comparison, which says more about the literature than the finding.
What is known about the weekly subcutaneous auto-injector?
It has been studied in three published cohorts, and it is not available in Canada: the single-use subcutaneous enanthate auto-injector is authorized only in the United States, under NDA 209863, verified 14 September 2026.
Kaminetsky 2019 in The Journal of Urology followed 150 hypogonadal men for 52 weeks on weekly subcutaneous doses of 50, 75 or 100 mg. At week 12, 92.7 percent had an average total testosterone of 300 to 1,100 ng/dL, with a mean of 553.3 ng/dL, and mean trough at week 52 was 487.2 ng/dL. The most frequent treatment emergent events were increased hematocrit, hypertension and increased prostate specific antigen, which led to discontinuation in 30 men.
Gittelman 2019 in The Journal of Sexual Medicine added ambulatory blood pressure monitoring in 133 men over 26 weeks. Adverse drug reactions occurred in 25.6 percent, most commonly a hematocrit at or above 52 percent, in 7.5 percent of men. By week 26, clinic systolic pressure had risen 3.4 mm Hg and diastolic 1.8 mm Hg. At week 12, ambulatory monitoring showed 24-hour systolic up 3.7 mm Hg and diastolic up 1.3 mm Hg. That trial is the basis of the blood pressure boxed warning carried by the United States product.
Choi 2021 in the International Journal of Impotence Research reported post-market experience in 110 men over 6 weeks: total testosterone rose from 246.6 to 538.4 ng/dL (p less than 0.001), 91.8 percent exceeded 300 ng/dL, no patient had a hematocrit above 54 percent, and mean prostate specific antigen rose from 1.07 to 1.18 (p = 0.01).
Published injectable findings at a glance
| Study | Population | Finding | Source |
|---|---|---|---|
| Dobs 1999, Journal of Clinical Endocrinology and Metabolism | 66 hypogonadal men, 24 weeks, enanthate 200 mg intramuscularly every 2 weeks | Supraphysiological levels for several days after each injection; normal range in 19 to 84 percent versus 77 to 100 percent on patch; luteinizing hormone subnormal in 31 percent versus 0 percent | PMID 10522982 |
| Choi 2021, The Journal of Urology | 234 men, 100 mg weekly, 12 weeks | Trough 313.6 to 536.4 ng/dL intramuscular, 246.6 to 552.8 ng/dL subcutaneous; modality not associated with total testosterone (p = 0.057); lower estradiol and hematocrit subcutaneously | PMID 34694927 |
| Kaminetsky 2019, The Journal of Urology | 150 men, weekly subcutaneous auto-injector, 52 weeks | 92.7 percent within 300 to 1,100 ng/dL at week 12; mean trough 487.2 ng/dL at week 52; 30 discontinuations | PMID 30296416 |
What is known about the long-acting undecanoate injection?
It is the only testosterone product with a restricted distribution program in the United States, and it has never been authorized in Canada, where every testosterone undecanoate product with a DIN is an oral capsule, verified 14 September 2026.
The reason for the restriction is pulmonary oil microembolism and anaphylaxis. The United States label for the long-acting injection (NDA 022219) states the product is available only through a restricted program under a Risk Evaluation and Mitigation Strategy because of those risks, and requires observation in the healthcare setting for 30 minutes after every injection.
Pastuszak 2020 in Sexual Medicine reviewed postmarketing safety across 90,092 doses distributed over 4.3 years. Of 633 case safety reports, 28 were classified as pulmonary oil microembolism, a yearly spontaneously reported rate of less than 0.1 percent per injection. Most events resolved (21 of 22), most within 30 minutes or less (13 of 17), and more than 60 percent required no medical intervention. In 3 of the 4 cases serious enough for an emergency visit, injection technique or dosing was a potential contributing factor. The authors note that postmarketing data are typically underreported and retrospective.
Adam 2022 in the International Journal of Impotence Research reviewed 29 studies covering 7,978 patients. Eight studies reported 88 cases of pulmonary oil microembolism or cough, and one post market review reported 223 cases per 3,107,652 injections. Almost all resolved spontaneously within 60 minutes, and the authors concluded the event was rare.
Ong 2012 in Case Reports in Medicine describes a single anaphylaxis case in which skin testing identified benzyl benzoate, the vehicle, as the trigger rather than the castor oil or the testosterone undecanoate.
What does the evidence say about testosterone injection frequency?
Very little, which is the honest answer. No randomized trial compares injection frequencies of the same short-acting ester: there is no trial of weekly against every-two-week cypionate, and none of split or daily schedules.
The only retrieved study quantifying the effect of shortening an interval is a simulation. Pastuszak 2021 in the Journal of Clinical Pharmacology modelled 8-week against 10-week maintenance intervals for 750 mg of undecanoate and predicted an 11 percent increase in average and trough concentration, a 5 percent increase in maximum concentration, and about a 10 percent increase in the proportion of patients with a trough above 300 ng/dL, with low likelihood of a maximum above 2500 ng/dL. Those figures are simulated, not observed.
Nothing above tells any individual what interval suits them. That is a conversation for a prescriber, alongside the bloodwork described in testosterone therapy monitoring in Canada.
How often do testosterone injections raise hematocrit?
Often enough that it is the main monitored harm. Nackeeran 2022 in The Journal of Urology, a Bayesian network meta-analysis of 29 placebo-controlled randomized trials in 3,393 men, found a mean hematocrit increase versus placebo of 4.0 percent (95 percent credible interval 2.9 to 5.1) for intramuscular enanthate or cypionate, against 3.0 percent for gel, 1.6 percent for intramuscular undecanoate and 1.4 percent for the patch. Only the difference between the intramuscular short esters and the patch reached significance, and the authors stated that the clinical concern of this increase remains questionable.
Hajjar 1997 in the Journal of Clinical Endocrinology and Metabolism followed 45 men on 200 mg of enanthate or cypionate every 2 weeks for 2 years. Eleven men, 24 percent, developed polycythemia requiring phlebotomy or temporary withholding, a third of those within the first year, and about a third of all subjects discontinued therapy.
Liu 2025 in Blood Advances reviewed 45 studies, 35 of them on testosterone and other androgens, and reported erythrocytosis rates of up to 66.7 percent, with intramuscular formulations, higher doses and older age associated with increased risk. It also reported that up to 2.7 percent of men on testosterone therapy developed thromboembolic events. Formulation-by-formulation figures are in hematocrit and testosterone by formulation.
Which testosterone injections are available in Canada?
Two, and both are short-acting intramuscular products. The Health Canada Drug Product Database, queried 14 September 2026, lists Taro-Testosterone Cypionate Injection 100 mg/mL, DIN 02496003, and Testosterone Enanthate Injection USP 200 mg/mL from Hikma Canada, DIN 02536315, as the only marketed injectables.
Both brand injectables were cancelled during 2025: Depo-Testosterone, DIN 00030783, on 18 July 2025, and Delatestryl, DIN 00029246, on 18 December 2025. A further cypionate 100 mg/mL product, DIN 02570122, was approved on 20 July 2026 but is not yet marketed, and approved is not the same as available.
Nothing else injectable is sold here: no long-acting undecanoate injection, no subcutaneous auto-injector, no mixed-ester product. The full list is in which testosterone products are available in Canada.
What the evidence does not show
- It does not show that subcutaneous dosing raises testosterone more than intramuscular dosing. In Choi 2021, with 234 men, modality was not associated with total testosterone after regression (p = 0.057), and the study was not randomized, with route and ester confounded.
- It does not show which injection frequency is better. No randomized trial compares injection frequencies of the same short-acting ester, and the only interval comparison retrieved, Pastuszak 2021, is a simulation.
- It does not show that injections are distinguishable from most other forms on hematocrit. In Nackeeran 2022, across 3,393 men, only the comparison against the patch reached significance.
- It does not show that the auto-injector findings transfer to Canadian practice. All three cohorts used a product authorized only in the United States, and 30 of the 150 men in the 52-week study discontinued for hematocrit, hypertension or prostate specific antigen changes.
- It does not quantify pulmonary oil microembolism precisely. Pastuszak 2020 rests on spontaneous reports the authors call typically underreported and retrospective.
- It does not show these products are free of cardiovascular signals. Gittelman 2019 measured a clinic systolic rise of 3.4 mm Hg by week 26 and a 24-hour ambulatory systolic rise of 3.7 mm Hg at week 12.
Frequently asked questions
Is subcutaneous injection better than intramuscular?
The evidence does not establish that. Choi 2021 in The Journal of Urology compared 234 men over 12 weeks and found the modality was not associated with total testosterone after regression (p = 0.057), although subcutaneous use was independently associated with lower estradiol and lower hematocrit (both p less than 0.001). The study was not randomized, and the route and the ester changed together between arms.
How often should testosterone injections be given?
No trial answers that. No randomized trial compares injection frequencies of the same short-acting ester, so there is no evidence comparing weekly with every-two-week dosing. The only retrieved interval comparison, Pastuszak 2021 in the Journal of Clinical Pharmacology, is a simulation of 8-week against 10-week undecanoate dosing that predicted an 11 percent increase in average and trough concentration. Injection schedules are a matter for your prescriber.
Can I get the weekly auto-injector or the long-acting injection in Canada?
No. The subcutaneous enanthate auto-injector is authorized only in the United States under NDA 209863, and the long-acting undecanoate injection has never been authorized in Canada, both verified on 14 September 2026. Every testosterone undecanoate product with a Canadian DIN is an oral capsule. Canada’s only marketed injectables are a cypionate 100 mg/mL solution and an enanthate 200 mg/mL solution.
How common is a high hematocrit on injections?
It is the most frequently measured harm. Hajjar 1997 in the Journal of Clinical Endocrinology and Metabolism found 11 of 45 men (24 percent) on two-weekly enanthate or cypionate for 2 years developed polycythemia requiring phlebotomy or temporary withholding. Liu 2025 in Blood Advances reported erythrocytosis rates of up to 66.7 percent across 45 studies, and thromboembolic events in up to 2.7 percent of men.
What is pulmonary oil microembolism?
It is a reaction in which oil from an injection reaches the lungs, reported with the long-acting undecanoate injection that Canada has never authorized. Pastuszak 2020 in Sexual Medicine identified 28 cases among 633 reviewed reports across 90,092 doses, below 0.1 percent per injection, with most resolving within 30 minutes. Adam 2022 reviewed 29 studies and 7,978 patients and concluded the event was rare.
References
- Dobs AS, et al. 1999. Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. Journal of Clinical Endocrinology and Metabolism. PMID 10522982. DOI: https://doi.org/10.1210/jcem.84.10.6078
- Choi EJ, et al. 2021. Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate. The Journal of Urology. PMID 34694927. DOI: https://doi.org/10.1097/JU.0000000000002301
- Kaminetsky JC, et al. 2019. A 52-Week Study of Dose Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-Injector. The Journal of Urology. PMID 30296416. DOI: https://doi.org/10.1016/j.juro.2018.09.057
- Gittelman M, et al. 2019. Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study. The Journal of Sexual Medicine. PMID 31551193. DOI: https://doi.org/10.1016/j.jsxm.2019.08.013
- Choi EJ, et al. 2021. Post-market safety and efficacy profile of subcutaneous testosterone enanthate-autoinjector. International Journal of Impotence Research. PMID 34007063. DOI: https://doi.org/10.1038/s41443-021-00435-6
- Kaminetsky J, et al. 2015. Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single-Use Autoinjector. Sexual Medicine. PMID 26797061. DOI: https://doi.org/10.1002/sm2.80
- Pastuszak AW, et al. 2020. Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis. Sexual Medicine. PMID 32184081. DOI: https://doi.org/10.1016/j.esxm.2020.01.009
- Adam M, et al. 2022. Occurrence of pulmonary oil microembolism (POME) with intramuscular testosterone undecanoate injection: literature review. International Journal of Impotence Research. PMID 35610506. DOI: https://doi.org/10.1038/s41443-022-00585-1
- Ong GS, et al. 2012. Anaphylaxis triggered by benzyl benzoate in a preparation of depot testosterone undecanoate. Case Reports in Medicine. PMID 22272209. DOI: https://doi.org/10.1155/2012/384054
- Pastuszak AW, et al. 2021. Population Pharmacokinetic Modeling and Simulations to Evaluate a Potential Dose Regimen of Testosterone Undecanoate. Journal of Clinical Pharmacology. PMID 34269421. DOI: https://doi.org/10.1002/jcph.1939
- Nackeeran S, et al. 2022. The Effect of Route of Testosterone on Changes in Hematocrit: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Trials. The Journal of Urology. PMID 34445892. DOI: https://doi.org/10.1097/JU.0000000000002188
- Hajjar RR, et al. 1997. Journal of Clinical Endocrinology and Metabolism. PMID 9360543. DOI: https://doi.org/10.1210/jcem.82.11.4387
- Liu K, et al. 2025. Diagnosis, management, and outcomes of drug-induced erythrocytosis: a systematic review. Blood Advances. PMID 39913688. DOI: https://doi.org/10.1182/bloodadvances.2024015410
- Health Canada. Drug Product Database. Queried 14 September 2026. https://health-products.canada.ca/dpd-bdpp/search/
- Health Canada. Product Monograph, oral testosterone undecanoate capsules. Authorized 12 December 2025. https://pdf.hres.ca/dpd_pm/00082762.PDF
- United States Food and Drug Administration. Drugs@FDA. Queried 14 September 2026. https://www.accessdata.fda.gov/scripts/cder/daf/
This page is educational information, not medical advice. Testosterone is a prescription medication and a controlled substance in Canada. Talk to your doctor or pharmacist about your own situation.