Testosterone replacement therapy
Also known as: TRT
Medically reviewed by Hormone Journal Editorial Team · Last reviewed 2026-05-22
Testosterone replacement therapy (TRT) is a medical treatment for hypogonadism that restores testosterone to normal levels, affecting roughly 2–4% of adult men.
What it is
Testosterone replacement therapy (TRT) is a prescribed medical treatment for hypogonadism — a condition in which the body fails to produce adequate testosterone — affecting an estimated 2–4% of adult men, with prevalence rising to roughly 20% in men over 60. Also called androgen replacement therapy, TRT restores circulating testosterone to the normal physiological range (typically 8–29 nmol/L by Canadian laboratory standards) through injections, topical gels, transdermal patches, or subcutaneous pellets. In Canada, testosterone products are regulated by Health Canada and require a prescription; testing is widely available through LifeLabs and Dynacare using a morning serum total testosterone draw.
Testosterone is the primary male sex hormone, produced mainly in the testes under pituitary control. It governs muscle mass, bone density, red blood cell production, libido, mood, and fat distribution. Levels peak in early adulthood and decline at roughly 1–2% per year after age 30–40. That gradual decline is normal aging; TRT is indicated only when levels fall below the clinical threshold AND the patient has symptoms — not for age-related decline alone.
Causes and mechanism
Hypogonadism is classified into two types:
| Type | Origin | Common causes |
|---|---|---|
| Primary (hypergonadotropic) | Testes | Klinefelter syndrome, orchitis, chemotherapy, trauma |
| Secondary (hypogonadotropic) | Pituitary / hypothalamus | Pituitary adenoma, obesity, opioid use, chronic illness |
In primary hypogonadism, the testes cannot respond to luteinizing hormone (LH); in secondary hypogonadism, the pituitary fails to send adequate LH signal. TRT bypasses both defects by delivering exogenous testosterone directly. Because exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis via negative feedback, it also suppresses endogenous sperm production — a key consideration for men who want to preserve fertility.
Symptoms and diagnosis
Symptoms of low testosterone (hypogonadism) include reduced libido, erectile dysfunction, fatigue, depressed mood, decreased muscle mass, increased visceral fat, and reduced bone mineral density. These overlap substantially with other conditions — thyroid disorders, depression, obstructive sleep apnea, and type 2 diabetes can all produce similar presentations.
Diagnosis requires at least two morning fasting serum total testosterone measurements below the laboratory reference range, combined with clinical symptoms. The Endocrine Society recommends against routine screening in asymptomatic men. Free testosterone or bioavailable testosterone may be measured when sex hormone-binding globulin (SHBG) is suspected to be abnormal (e.g., in obesity or liver disease). In Canada, these tests are OHIP-billable when ordered for a documented clinical indication; coverage varies by province for follow-up monitoring.
Treatment options
Available TRT formulations differ in dosing frequency, cost, and side-effect profile:
| Formulation | Typical dosing | Notes |
|---|---|---|
| Intramuscular injection (testosterone cypionate / enanthate) | Every 1–2 weeks | Low cost; covered by most provincial drug plans with prior authorization |
| Subcutaneous injection | Weekly or twice-weekly | Smaller volume, steadier levels; increasingly preferred |
| Topical gel (AndroGel, Testim) | Daily | Convenient; transfer risk to partners/children |
| Transdermal patch (Androderm) | Daily | Skin irritation common |
| Subcutaneous pellet | Every 3–6 months | Not widely available in Canada; not covered by most provincial formularies |
Documented benefits in men with confirmed hypogonadism include improved sexual desire and erectile function, increased lean muscle mass, improved bone mineral density, and better insulin sensitivity. A 2025 systematic review in Cureus found consistent improvements across these domains when TRT was used in appropriately selected patients aged 50 and above.
For men with secondary hypogonadism who wish to preserve fertility, alternatives such as clomiphene citrate or human chorionic gonadotropin (hCG) stimulate endogenous testosterone production without suppressing spermatogenesis.
When to see a clinician in Canada
See a family physician or endocrinologist if you have persistent symptoms of low testosterone — particularly reduced libido, unexplained fatigue, and loss of muscle mass — lasting more than a few months. A referral to endocrinology or urology is appropriate when the cause of hypogonadism is unclear, when fertility preservation is a concern, or when initial treatment does not achieve target levels.
In Canada, TRT is initiated and monitored by physicians; some patients access prescriptions through virtual care platforms (Felix, Maple, Phoenix, Cleo, and others), though in-person assessment is generally recommended before starting therapy. Monitoring typically includes serum testosterone, hematocrit, PSA (in men over 40), and liver enzymes at 3 months after initiation and then annually.
Limitations and open questions
Research is still emerging on several important questions. The cardiovascular safety of long-term TRT remains debated: the 2023 TRAVERSE trial (5,246 men) found no significant increase in major adverse cardiovascular events over a median 33-month follow-up, but longer-term data are limited. The relationship between TRT and prostate cancer risk has not been definitively resolved; current evidence does not support a causal link, but TRT remains contraindicated in men with active or suspected prostate cancer.
Health Canada has not issued specific guidance on TRT for age-related testosterone decline in otherwise healthy men, and most provincial drug benefit programs require documented hypogonadism for coverage. The optimal testosterone target range, ideal formulation for long-term use, and effects on cognitive function and mood in older men are all areas where evidence remains incomplete. TRT in transgender men is a distinct clinical context with its own evidence base and is not fully addressed here.
FAQs
How is TRT different from anabolic steroid use?
TRT uses physician-prescribed testosterone doses calibrated to restore levels to the normal physiological range (8–29 nmol/L in most Canadian labs), whereas anabolic steroid use typically involves supraphysiological doses — often 10–100 times higher — taken without a medical indication. The health risks differ substantially: supraphysiological doses carry much greater risks of cardiovascular harm, liver toxicity, and severe hormonal suppression. TRT is a regulated medical treatment; non-prescribed anabolic steroid use is illegal in Canada under the Controlled Drugs and Substances Act.
Will TRT affect my fertility?
Yes — exogenous testosterone suppresses the pituitary signals (LH and FSH) that drive sperm production, and most men on TRT experience significant reductions in sperm count, sometimes to zero. This effect is generally reversible after stopping TRT, but recovery can take 6–18 months and is not guaranteed. Men who want to father children should discuss fertility-preserving alternatives such as clomiphene citrate or hCG injections with their physician before starting TRT.
Is testosterone replacement therapy covered by provincial drug plans in Canada?
Coverage varies by province and formulation. Injectable testosterone (cypionate or enanthate) is listed on most provincial formularies and is generally the lowest-cost option, often requiring prior authorization confirming a diagnosis of hypogonadism. Topical gels and patches are covered in some provinces but not others, and subcutaneous pellets are rarely covered. Patients should check their specific provincial drug benefit program (e.g., Ontario Drug Benefit, BC PharmaCare, RAMQ in Quebec) and confirm coverage before starting a particular formulation.
What are the main risks of testosterone replacement therapy?
The most common risks include erythrocytosis (elevated red blood cell count, occurring in roughly 5–10% of users), acne, testicular atrophy, and reduced sperm production. Fluid retention and gynecomastia (breast tissue growth) can occur. TRT is contraindicated in men with active prostate cancer, breast cancer, untreated severe obstructive sleep apnea, or a hematocrit above 54%. The 2023 TRAVERSE trial (5,246 participants) did not find a significant increase in major cardiovascular events over approximately 33 months, but long-term cardiovascular data beyond 3 years remain limited.
How long does it take for TRT to work?
Different effects emerge on different timelines. Libido and mood improvements are often noticed within 3–6 weeks. Changes in muscle mass and body composition typically become measurable after 3–6 months of consistent therapy. Bone mineral density improvements may take 1–2 years to show on DEXA scanning. Clinicians in Canada generally reassess serum testosterone levels and symptom response at 3 months after initiation to confirm that target levels have been reached and to check for early side effects such as elevated hematocrit.
Sources
- Testosterone therapy: Potential benefits and risks as you age
- The benefits and risks of testosterone replacement therapy: a review
- Testosterone Replacement Therapy in Men Aged 50 and Above: A Narrative Review of Evidence-Based Benefits, Safety Considerations, and Clinical Recommendations
- Impact of Testosterone on Male Health: A Systematic Review
- Testosterone Deficiency in Adults and Testosterone Therapy — Endocrine Society Clinical Practice Guideline
- Health Canada Drug Product Database — Testosterone