Testosterone Replacement Therapy Guidelines

Introduction to Testosterone Therapy

• The goal of testosterone therapy is to normalize total testosterone levels to the middle tertile of the normal reference range while improving symptoms, according to the American Urological Association 1

Monitoring and Safety Considerations

• Testosterone levels should be tested 2-3 months after treatment initiation and after any dose changes, as recommended by the American Gastroenterological Association 2, 3
• For patients on intramuscular testosterone injections, levels should be measured midway between injections, targeting a mid-normal value, as suggested by the American Gastroenterological Association 2, 3
• Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient, according to the American Gastroenterological Association 2, 3
• Testosterone therapy should not be commenced for a period of three to six months in patients with a history of cardiovascular events, as recommended by the American Urological Association 1
• Clinicians should not prescribe alkylated oral testosterone due to risk of liver toxicity, according to the American Urological Association 1
• There is evidence suggesting that testosterone injections may be associated with a greater risk of cardiovascular events compared to transdermal preparations, possibly due to increased time spent in both supratherapeutic and subtherapeutic ranges, as reported by the American Gastroenterological Association 2, 3
• Patients who are overweight or obese should be counseled regarding weight loss programs concurrent with testosterone therapy due to potential cardiovascular risks, as recommended by the American Urological Association 1
• Exogenous testosterone therapy should not be prescribed to men who are currently trying to conceive, as it can interrupt normal spermatogenesis, according to the American Urological Association 1

Alternative Therapies

• For men desiring to maintain fertility, alternatives to testosterone therapy include aromatase inhibitors, human chorionic gonadotropin, or selective estrogen receptor modulators, as suggested by the American Urological Association 1
• Transdermal preparations (gels, patches) offer more stable day-to-day testosterone levels and may be considered as an alternative to intramuscular injections, according to the American Gastroenterological Association 2, 3

Switching from Oral Testosterone Undecanoate to Topical Testosterone

Dosing Recommendations

• The American Urological Association recommends starting with standard initial doses of topical testosterone preparations, including 1.62% testosterone gel: 40.5 mg (2 pumps) applied once daily, 1% testosterone gel: 50 mg (one 5-g packet) applied once daily, and testosterone patches: 4 mg/day (two 2-mg patches) applied once daily 4, 5
• Clinicians should target a total testosterone level in the middle tertile of the normal reference range (450-600 ng/dL) using the minimal effective dose of topical testosterone 6

Monitoring Recommendations

• The Endocrine Society recommends targeting testosterone levels in the mid-normal range (450-600 ng/dL) for optimal efficacy and safety 6, 7
• For topical preparations, testosterone levels can be measured at any time after reaching steady state, as levels remain relatively stable throughout the day 4

Safety Considerations

• The American Heart Association recommends avoiding initiating testosterone therapy within 3-6 months of cardiovascular events 7
• Topical preparations may be preferable for patients with cardiovascular risk factors, as they provide more physiologic testosterone levels with less fluctuation 4
• Monitor for erythrocytosis, which occurs less frequently with topical preparations (2.8-17.9% depending on dose) compared to injectable testosterone (43.8%) 5
• Counsel patients that testosterone therapy should not be used in men trying to conceive due to suppression of spermatogenesis 6, 7

Application Instructions

• Apply topical testosterone to clean, dry skin of the shoulders, upper arms, or abdomen (depending on specific product instructions) 4
• Avoid washing the application site for at least 2 hours after application 4
• Inform patients about the risk of transfer to others and advise them to cover the application site with clothing after the gel has dried 7

Timing for Rechecking Testosterone Levels

Initial Monitoring and Long-Term Schedule

• For patients initiating or adjusting testosterone replacement therapy, recheck testosterone levels at 2-3 months after starting treatment or any dose change, then every 6-12 months once stable therapeutic levels are achieved, as recommended by The Journal of Urology 8
• Once stable therapeutic levels are confirmed, testosterone should be measured every 6-12 months during ongoing therapy, applicable to all forms of testosterone replacement therapy 8

Critical Timing Considerations

• Do not measure testosterone levels during testosterone rebound periods after stopping therapy, as values will not reflect true baseline status, according to The Journal of Urology 9
• Ensure serum testosterone concentration is relatively stable (ideally ≤10% variation) over the measurement period, and all PSA values used for monitoring should be obtained using the same assay, preferably at the same laboratory 9

Treatment Strategy Reassessment

• If patients achieve target testosterone levels but report no symptom improvement after 3-6 months, discuss cessation of therapy as there is no utility in continuing treatment without clinical benefit, as recommended by The Journal of Urology 8