📋 Key Information Summary
- Testosterone replacement therapy (TRT) is indicated for men with confirmed hypogonadism — consistently low serum testosterone (total T < 8 nmol/L on two morning samples) with associated symptoms.
- Hypogonadism may be primary (testicular failure) or secondary (hypothalamic–pituitary dysfunction); aetiology must be identified before initiating therapy.
- TRT is contraindicated in prostate cancer, breast cancer, uncontrolled heart failure, severe untreated obstructive sleep apnoea (OSA), polycythaemia (haematocrit > 0.54), and when fertility is desired.
- Australian PBS-listed options include testosterone undecanoate (Reandron® IM), testosterone enanthate (Primoteston Depot® IM), and testosterone undecanoate oral (Andriol Testocaps®).
- Transdermal testosterone (Testogel® 1% 50 mg sachets) is available but is not PBS-subsidised for most patients — authority required or private script.
- Initial monitoring: haematocrit, PSA, lipids, LFTs at baseline, 3 months, 6 months, then 6–12 monthly.
- Haematocrit > 0.54 requires dose reduction, phlebotomy, or cessation — thromboembolic risk increases significantly.
- PSA monitoring is essential; TRT is contraindicated in existing prostate cancer and a urology referral is required if PSA rises > 4.0 µg/L or increases by > 1.4 µg/L in 12 months.
- For men desiring fertility, TRT suppresses spermatogenesis via negative feedback on gonadotrophins — use clomiphene citrate or hCG instead.
- Late-onset hypogonadism (ageing-related) should be managed cautiously with lifestyle optimisation first; TRT only if sustained low levels with clear symptomatic benefit.
- Aboriginal and Torres Strait Islander men experience higher rates of chronic disease-related hypogonadism; culturally safe care, remote monitoring pathways, and PBS access are important considerations.
- Oral testosterone undecanoate must be taken with food containing at least 19 g of fat for adequate absorption — poor bioavailability with fasting.
🎧 Audio Brief
Introduction & Australian Epidemiology
Testosterone replacement therapy (TRT) is the cornerstone of management for men with confirmed hypogonadism — a clinical syndrome characterised by low circulating testosterone and associated symptoms including decreased libido, erectile dysfunction, fatigue, reduced muscle mass, increased adiposity, and mood disturbance.
The Endocrine Society of Australia and the Australasian Society of Clinical Immunology and Allergy (ASCIA) endorse that diagnosis requires both biochemical confirmation (total serum testosterone < 12 nmol/L on at least two early-morning fasting samples) and clinical symptomatology. Total testosterone between 8 and 12 nmol/L is considered equivocal and should prompt measurement of free testosterone or sex hormone-binding globulin (SHBG).
Australian epidemiology: Community-based studies estimate the prevalence of symptomatic hypogonadism at 5–8% of men aged 40–79 years, rising to 15–20% in men aged > 70 years. In the 2017–18 Australian Bureau of Statistics National Health Survey, testosterone prescribing increased approximately 4-fold over the preceding decade, with Reandron® (testosterone undecanoate 1000 mg IM) being the most commonly PBS-dispensed formulation. Chronic conditions prevalent in Australia — type 2 diabetes mellitus, obesity, opioid use, and obstructive sleep apnoea — are major contributors to functional hypogonadism.
Primary hypogonadism (hypergonadotrophic) accounts for approximately 30% of cases and includes Klinefelter syndrome (affecting ~1 in 600 Australian males), orchitis, testicular trauma, and cryptorchidism. Secondary hypogonadism (hypogonadotrophic) — including Kallmann syndrome, pituitary adenoma, and functional suppression — accounts for the remainder.
Indications & Contraindications
Indications for Testosterone Replacement Therapy
TRT is indicated when both biochemical and clinical criteria are met:
| Indication | Details |
|---|---|
| Primary hypogonadism | Klinefelter syndrome, bilateral anorchia, testicular torsion, orchidectomy, mumps orchitis, chemotherapy/radiation-induced gonadal failure |
| Secondary hypogonadism | Kallmann syndrome, idiopathic hypogonadotrophic hypogonadism, pituitary tumour/adenoma, hyperprolactinaemia (after treatment), haemochromatosis |
| Late-onset hypogonadism (LOH) | Age-related decline with total T consistently < 8 nmol/L and symptoms — use cautiously; lifestyle measures first |
| Functional hypogonadism | Obesity, type 2 DM, chronic opioid therapy, glucocorticoid use, HIV-related wasting — treat underlying cause first where possible |
Diagnostic Criteria
- Total serum testosterone < 8 nmol/L on two separate morning (8–10 am) fasting samples — confirms hypogonadism
- Total testosterone 8–12 nmol/L — equivocal zone: calculate free testosterone (using Vermeulen equation) or measure bioavailable testosterone
- Elevated LH and FSH → primary hypogonadism
- Normal or low LH and FSH → secondary hypogonadism → investigate pituitary (MRI pituitary, prolactin, iron studies)
- Prolactin > 1000 mIU/L → exclude prolactinoma before starting TRT
Absolute Contraindications
- Prostate cancer (known or suspected) — testosterone may stimulate growth
- Male breast cancer
- Polycythaemia with haematocrit > 0.54
- Uncontrolled or severe congestive heart failure (NYHA class III–IV)
- Desire for fertility in the next 6–12 months
- Hypersensitivity to testosterone or formulation excipients
Relative Contraindications / Cautions
- Severe untreated obstructive sleep apnoea — may worsen OSA; treat CPAP first
- Lower urinary tract symptoms (IPSS > 19) — monitor closely
- PSA > 4.0 µg/L without urological work-up
- Thrombophilia or history of venous thromboembolism (VTE)
- Epilepsy — testosterone may lower seizure threshold
- Severe hepatic impairment
Formulations & Dosing
The choice of formulation depends on patient preference, PBS availability, injection tolerance, and clinical context. The following formulations are available in Australia:
Testosterone Undecanoate
Reandron® · IM injection · Long-acting
Adult dose
1000 mg IM deep gluteal injection; loading dose at week 0, then week 6, then every 10–14 weeks
Paediatric dose
Not established in < 18 years (use specialist guidance)
Route / Frequency
Intramuscular (gluteal only — risk of pulmonary oil microembolism if given IV); q10–14 weeks
Renal adjustment
No dose adjustment required
Hepatic adjustment
Avoid in severe hepatic impairment
PBS status
✔ PBS General Benefit
Testosterone Enanthate
Primoteston Depot® · IM injection · Medium-acting
Adult dose
250 mg IM every 2–3 weeks (adjust based on trough levels)
Paediatric dose
50–100 mg IM every 2–4 weeks for delayed puberty (specialist only)
Route / Frequency
Intramuscular (deltoid or gluteal); q2–3 weeks
Renal adjustment
No dose adjustment required
Hepatic adjustment
Avoid in severe hepatic impairment
PBS status
✔ PBS General Benefit
Testosterone Undecanoate (Oral)
Andriol Testocaps® · Oral capsule · Lymphatic absorption
Adult dose
120–160 mg PO daily in 2 divided doses with meals containing ≥ 19 g fat
Important note
Must be taken with food containing fat — fasting absorption is negligible
Route / Frequency
Oral, twice daily with meals
Renal adjustment
No dose adjustment required
Hepatic adjustment
Avoid in hepatic impairment
PBS status
✔ PBS General Benefit
Testosterone Gel 1%
Testogel® 50 mg sachets · Transdermal · Not PBS-subsidised
Adult dose
50 mg (1 sachet) applied daily to shoulders/upper arms; may increase to 75–100 mg based on levels
Important note
Risk of secondary transfer to women and children — cover application site; wash hands thoroughly
Route / Frequency
Transdermal, daily application; allow to dry before dressing
Renal adjustment
No dose adjustment required
PBS status
✘ Not PBS-subsidised — private prescription or authority in select cases
Pulmonary oil microembolism (POME): Reandron® and Primoteston® must be injected deep into the gluteal muscle only. Intravascular injection can cause POME — symptoms include cough, dyspnoea, chest tightness, and syncope. Observe patients for 30 minutes post-injection. Never inject IV.
Target Serum Levels
The therapeutic target is a mid-range total testosterone of 15–20 nmol/L measured at trough (just before next injection) for injectable formulations. Avoid supraphysiological levels (> 30 nmol/L) which increase adverse effects without additional benefit.
Monitoring & Side Effects
Recommended Monitoring Schedule
Baseline
Total testosterone (×2 morning samples), FSH, LH, prolactin, SHBG, FBC with haematocrit, PSA, LFTs, fasting lipids, fasting glucose/HbA1c, bone density (DEXA if primary hypogonadism), IPSS questionnaire
3 months
Total testosterone (trough), haematocrit, PSA, symptom assessment, injection site review
6 months
Total testosterone, haematocrit, PSA, LFTs, fasting lipids, symptom assessment
Every 6–12 months
Total testosterone, haematocrit, PSA, LFTs, lipids, FBC, DEXA (if indicated), symptom reassessment, cardiovascular risk review
Key Side Effects & Management
| Side Effect | Mechanism | Management |
|---|---|---|
| Polycythaemia (haematocrit > 0.54) | Erythropoietin stimulation | Dose reduction, therapeutic phlebotomy, or stop TRT |
| Acne / oily skin | Sebaceous gland stimulation | Topical agents; dose reduction if severe |
| Gynaecomastia | Peripheral aromatisation to oestradiol | Dose reduction; consider tamoxifen if symptomatic |
| Peripheral oedema | Fluid retention via mineralocorticoid effect | Reduce dose; diuretics if needed |
| Sleep apnoea worsening | Upper airway effects | Optimise CPAP; consider dose reduction |
| Infertility | GnRH suppression → ↓ LH/FSH | Stop TRT; use hCG or clomiphene if fertility desired |
| Mood / behavioural changes | CNS androgen receptor effects | Dose titration; psychiatric review if significant |
| Injection site pain / reaction | Oil-based depot formulation | Rotate sites; switch formulation if persistent |
Stop TRT and refer urgently if: haematocrit > 0.54, PSA > 4.0 µg/L (or rise > 1.4 µg/L/year), symptoms of VTE (leg swelling, chest pain, dyspnoea), or signs of hepatic dysfunction.
Prostate Monitoring Detail
- Digital rectal examination (DRE) at baseline and annually
- PSA at baseline, 3 months, 6 months, then annually
- Refer to urology if PSA > 4.0 µg/L or velocity > 0.4 µg/L/year on two occasions
- TRT does not cause prostate cancer but may accelerate pre-existing occult disease
- Men on active surveillance for prostate cancer — TRT generally contraindicated; specialist decision only
Special Situations (Fertility, Ageing)
Fertility Preservation
TRT suppresses spermatogenesis. Exogenous testosterone exerts negative feedback on hypothalamic GnRH, reducing LH and FSH secretion. Sperm production may be completely abolished. Men wishing to conceive in the next 6–12 months should not receive TRT.
Alternatives for hypogonadal men desiring fertility:
Clomiphene Citrate
Clomid® · Off-label in men · SERM
Adult dose
25–50 mg PO daily; blocks oestrogen negative feedback → ↑ LH/FSH → ↑ intratesticular testosterone → maintains spermatogenesis
PBS status
⚠ Not PBS for male hypogonadism — off-label; private script
hCG (Human Chorionic Gonadotrophin)
Pregnyl® · IM or SC injection · LH analogue
Adult dose
1000–2000 IU SC or IM 2–3 times per week; stimulates intratesticular testosterone production
PBS status
✔ PBS General Benefit (for gonadotrophin deficiency)
Recovery of spermatogenesis after discontinuing TRT may take 6–24 months and is unpredictable. Semen analysis should be performed before restarting TRT if fertility was previously desired. Pre-treatment sperm banking should be discussed with all men of reproductive age.
Late-Onset Hypogonadism (Ageing)
Testosterone levels decline approximately 1–2% per year after age 30. Late-onset hypogonadism (LOH) is characterised by total testosterone < 11 nmol/L (or free testosterone < 225 pmol/L) in conjunction with at least three sexual symptoms (decreased libido, erectile dysfunction, reduced morning erections).
Management approach for older men:
- Step 1 — Lifestyle optimisation: Weight loss (5–10% body weight can increase testosterone by 2–3 nmol/L), resistance exercise, sleep hygiene, alcohol reduction, opioid weaning if applicable
- Step 2 — Re-evaluate at 3–6 months: If persistent symptomatic low testosterone (total T < 8 nmol/L on repeat testing), consider TRT
- Step 3 — Cardiovascular risk assessment: The TRAVERSE trial (2023) demonstrated no significant increase in major adverse cardiovascular events (MACE) with TRT in men aged 45–80 years with cardiovascular risk factors — but polycythaemia management remains critical
- Avoid routine TRT for age-related decline without clear biochemical and symptomatic criteria — "well man" testosterone use is not evidence-based
Opioid-Induced Hypogonadism
Chronic opioid use suppresses GnRH pulsatility, causing secondary hypogonadism in up to 75% of men on long-term opioid therapy. Management priorities:
- Opioid dose reduction or rotation where possible
- TRT if symptomatic hypogonadism persists after opioid optimisation
- Monitor closely — polypharmacy interactions and fall risk in older patients
Investigations
The following investigations are recommended before initiating TRT:
Essential
Total serum testosterone (×2 morning fasting samples)
Collect between 8–10 am after overnight fast. MBS Item 66782. Validated immunoassay or LC-MS/MS preferred.
Essential
SHBG and calculated free testosterone
Use Vermeulen equation if total T is 8–12 nmol/L (equivocal zone).
Essential
LH and FSH
Differentiates primary (↑ gonadotrophins) from secondary (normal/↓) hypogonadism.
Essential
FBC with haematocrit
Baseline polycythaemia is a contraindication. Haematocrit > 0.54 = do not start TRT.
Essential
PSA (prostate-specific antigen)
Baseline and follow-up. Age-specific reference ranges. DRE recommended.
Available
Prolactin
Elevated prolactin may indicate pituitary pathology. Refer if > 1000 mIU/L.
Available
Fasting lipids and glucose / HbA1c
Metabolic syndrome screening; TRT may improve insulin sensitivity and lipid profile.
Available
LFTs (liver function tests)
Exclude hepatic causes; baseline for monitoring oral formulations.
Referral
MRI pituitary
If secondary hypogonadism confirmed — exclude pituitary adenoma, especially if prolactin elevated or other pituitary hormone deficiencies present.
Referral
DEXA bone density scan
Recommended for primary hypogonadism (e.g., Klinefelter) and men with fractures. MBS-rebated if criteria met.
Available
Iron studies
Haemochromatosis screening — a treatable cause of secondary hypogonadism.
Available
Semen analysis
Baseline fertility assessment for men of reproductive age before TRT initiation.
Special Populations
Paediatrics
Indication: Delayed puberty, Klinefelter syndrome, anorchia
Testosterone enanthate: 50–100 mg IM every 2–4 weeks, titrated to pubertal milestones
Monitoring: Growth velocity, bone age (wrist X-ray), pubertal staging (Tanner), haematocrit
Endocrinologist-supervised only. Goal is physiological virilisation, not supraphysiological levels.
Pregnancy / Reproductive Partners
Secondary transfer: Transdermal gels pose risk to pregnant women and children — testosterone can cause virilisation of female foetuses
Precautions: Cover application site, wash hands, avoid skin-to-skin contact for 6 hours, do not let children touch gel site
Consider IM formulations in households with pregnant partners or young children to eliminate transfer risk.
Elderly (≥ 65 years)
Cardiovascular: TRAVERSE trial supports cardiovascular safety in men 45–80 with existing CV risk — but individualise
Polycythaemia: Higher baseline risk; monitor haematocrit more frequently (every 3 months initially)
Falls: Monitor for fluid retention, mood lability, and polypharmacy effects
Start at standard dose; avoid supraphysiological trough levels (> 25 nmol/L) in older men.
Renal Impairment
CKD stages 1–3: No dose adjustment required
CKD stages 4–5 / dialysis: Use with caution; no formal dose adjustment data — start at lower dose and monitor haematocrit closely
Erythropoietin-stimulating agents (ESAs) in CKD patients may compound polycythaemia risk when combined with TRT.
Hepatic Impairment
Mild: Use with caution; monitor LFTs closely
Moderate–severe: Avoid oral testosterone (first-pass metabolism). Prefer parenteral (IM) formulations
Hepatocellular carcinoma: Absolute contraindication to TRT
Oral 17α-alkylated testosterone preparations (not used in Australia) are most hepatotoxic. Reandron® and Primoteston® are safer in mild hepatic disease.
Immunocompromised
HIV-related hypogonadism: Common (up to 50% of men with advanced HIV). TRT improves lean body mass and quality of life
Drug interactions: No significant interactions with ART; monitor lipids (some ART regimens cause dyslipidaemia)
TRT is PBS-subsidised for documented hypogonadism in HIV-positive men.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
📚 References
- 1. Yeap BB, Grossmann M, McLachlan RI, et al. Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy. Medical Journal of Australia. 2016;205(4):173-178.
- 2. Grossmann M, Ng Tang Fui M, Cheung AS. Late-onset hypogonadism — testosterone therapy in older men. Medical Journal of Australia. 2020;212(8):367-372.
- 3. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. New England Journal of Medicine. 2023;389(2):107-117. (TRAVERSE trial)
- 4. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 2018;103(5):1715-1744.
- 5. Grossmann M, Matsumoto AM. A perspective on middle-aged and older men with functional hypogonadism: focus on holistic management. Journal of Clinical Endocrinology & Metabolism. 2017;102(3):1067-1075.
- 6. Australian Institute of Health and Welfare (AIHW). The health of Aboriginal and Torres Strait Islander peoples 2023. AIHW, Canberra. 2023.
- 7. Australian Government Department of Health. Pharmaceutical Benefits Scheme — Testosterone. Available at: pbs.gov.au. Accessed 2024.
- 8. Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S, Punab M. Guidelines on male hypogonadism. European Association of Urology. 2023.
- 9. Tajar A, Forti G, O'Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. Journal of Clinical Endocrinology & Metabolism. 2010;95(4):1810-1818.
- 10. Royal Australian College of General Practitioners (RACGP). RACGP aged care clinical guide (Silver Book) — Endocrinology. 6th edition. 2023.
- 11. Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Practice & Research Clinical Endocrinology & Metabolism. 2017;31(4):377-396.
- 12. Cheung AS, de Rooij M, Vlot MC, et al. Opioid-induced hypogonadism in men and women: a systematic review. The Lancet Diabetes & Endocrinology. 2022;10(8):587-598.