Testosterone

What it is

Testosterone is the primary androgen hormone in humans, declining roughly 1% per year after age 30 in men — a rate that can eventually produce clinically significant deficiency in an estimated 2–6% of adult males. Also called the principal male sex hormone or androgen, testosterone is produced mainly in the Leydig cells of the testes (about 95%) and, in smaller amounts, by the adrenal cortex in both sexes and by the ovaries in people assigned female at birth. In Canada, low testosterone (hypogonadism) is assessed through serum total testosterone testing available at national labs such as LifeLabs and Dynacare, with most Canadian clinical guidelines using a threshold of roughly 8–12 nmol/L to define deficiency in symptomatic men.

Testosterone is not exclusively a reproductive hormone. It regulates bone mineral density, lean muscle mass, red blood cell production, fat distribution, mood, and cognitive function. A small fraction of circulating testosterone is converted peripherally to estradiol — meaning some effects historically attributed to testosterone deficiency are partly driven by the accompanying decline in estrogen.

Causes and mechanism

Testosterone synthesis is governed by the hypothalamic-pituitary-gonadal (HPG) axis. The hypothalamus releases gonadotropin-releasing hormone (GnRH), which prompts the pituitary to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates testicular Leydig cells to produce testosterone; rising testosterone then feeds back to suppress further GnRH and LH release.

Deficiency arises from two broad categories:

Type	Origin	Common causes
Primary hypogonadism	Testes fail to produce adequate testosterone despite normal LH/FSH	Klinefelter syndrome, orchitis, chemotherapy, radiation
Secondary hypogonadism	Pituitary or hypothalamus fails to signal the testes	Pituitary adenoma, opioid use, obesity, hyperprolactinemia
Age-related (late-onset)	Gradual decline in both testicular and HPG-axis function	Normal aging, metabolic syndrome, type 2 diabetes

Obesity accelerates decline: adipose tissue converts testosterone to estradiol via aromatase, suppressing HPG-axis output. Chronic opioid use is an increasingly recognized cause of secondary hypogonadism in Canada, given high rates of opioid prescribing.

Symptoms and diagnosis

Symptoms of low testosterone overlap substantially with those of other conditions, which makes diagnosis dependent on both clinical presentation and laboratory confirmation.

Common symptoms include reduced libido, erectile dysfunction, fatigue, depressed mood, decreased muscle mass, increased visceral fat, and reduced bone density. Gynecomastia (breast tissue enlargement) can occur when the testosterone-to-estrogen ratio falls.

Diagnosis in Canada typically involves:

1. Morning serum total testosterone (two separate measurements on different days if the first is borderline)
2. LH and FSH to distinguish primary from secondary hypogonadism
3. Sex hormone-binding globulin (SHBG) and calculated free testosterone when total testosterone is borderline or SHBG is suspected to be abnormal
4. Prolactin, thyroid function, and CBC to rule out contributing conditions

Reference ranges vary by lab, but most Canadian laboratories report a normal adult male range of approximately 8.0–29.0 nmol/L for total testosterone.

Treatment options

Treatment is indicated for men with consistently low testosterone AND symptoms attributable to deficiency — not for age-related decline alone in otherwise healthy, asymptomatic men.

Testosterone replacement therapy (TRT) is available in several formulations in Canada:

• Topical gels/creams (e.g., AndroGel, Testim) — daily application; risk of transference to partners or children
• Intramuscular injections (testosterone cypionate or enanthate) — every 1–4 weeks; widely covered by provincial drug plans
• Subcutaneous pellets — inserted every 3–6 months; less commonly used in Canada
• Transdermal patches — daily; less popular due to skin reactions

TRT is contraindicated in men planning fertility in the near term, as exogenous testosterone suppresses sperm production. Men wishing to preserve fertility may instead use clomiphene citrate or human chorionic gonadotropin (hCG) to stimulate endogenous production.

Coverage varies by province: injectable testosterone is generally listed on provincial formularies (e.g., Ontario Drug Benefit, BC PharmaCare) for confirmed hypogonadism; gels may require special authorization. Canadian telehealth platforms including Felix, Maple, Cleo, Phoenix, and others now offer TRT assessment and prescribing, though patients should confirm that any prescription is supported by laboratory testing and follow-up monitoring.

When to see a clinician in Canada

See a family physician or endocrinologist if you have persistent fatigue, low libido, unexplained loss of muscle mass, or mood changes lasting more than a few weeks — particularly if you are over 40, have obesity, type 2 diabetes, or a history of opioid use. A referral to endocrinology or urology is appropriate when primary hypogonadism is suspected, prolactin is elevated, or TRT has not produced expected results. Bone density testing (DXA scan) is recommended for men with confirmed long-standing hypogonadism, as osteoporosis risk is elevated.

Limitations and open questions

Research is still emerging on several important questions. The testosterone threshold at which treatment becomes beneficial — rather than merely correcting a lab value — is not firmly established; a landmark 2013 NIH-funded study in the New England Journal of Medicine showed that different physiological functions are impaired at different testosterone levels, complicating any single cutoff. The long-term cardiovascular safety of TRT remains debated: earlier observational data raised concerns, but the 2023 TRAVERSE trial found no significant increase in major adverse cardiovascular events in men with hypogonadism and pre-existing cardiovascular risk. Health Canada has not issued updated prescribing guidance that fully incorporates TRAVERSE findings. The role of testosterone therapy in women — for low libido, fatigue, or menopause-related symptoms — is an active area of research; the SOGC and Endocrine Society acknowledge benefit for hypoactive sexual desire disorder in postmenopausal women, but long-term safety data remain limited. Optimal monitoring intervals, target levels during TRT, and the clinical significance of free versus total testosterone in borderline cases are all areas where Canadian clinical consensus is still developing.