Testosterone Replacement Therapy in Hypogonadal Males

Introduction

Testosterone replacement therapy is recommended for hypogonadal males to achieve a total testosterone level in the middle tertile of the normal reference range, specifically targeting 450-600 ng/dL, as recommended by the American Urological Association and the Endocrine Society 1, 2

Typical dosing ranges for long-acting injectable testosterone formulations include testosterone enanthate: 100-200 mg every 2 weeks or 50 mg weekly, and testosterone cypionate: 100-200 mg every 2 weeks or 50 mg weekly, for hypogonadal male replacement, as recommended by the American Gastroenterological Association guidelines 2
For self-administration, thigh injections are recommended; gluteal administration is preferred when injected by another person, according to the American Gastroenterological Association guidelines 2
Testosterone levels should be measured midway between injections to achieve a mid-normal value, as recommended by the American Gastroenterological Association guidelines 2
Typical dosing range for Androgel (testosterone gel) is AndroGel 1%: 50-100 mg/day and AndroGel 1.62%: 20.25-81 mg/day, according to the Endocrine Society 2
Maximum dose of 100 mg per day for transdermal preparations like Testim, and clinicians should consider alternative testosterone formulations rather than exceeding the recommended maximum dose if a patient is not achieving adequate symptom relief 2

Intramuscular testosterone injections are relatively inexpensive compared to other formulations, according to the American Gastroenterological Association guidelines 2
Intramuscular testosterone injections offer flexible/infrequent dosing, as stated by the American Gastroenterological Association guidelines 2
No risk of transference to others with intramuscular testosterone injections, as noted by the American Gastroenterological Association guidelines 2
Testosterone gel has benefits, including more stable day-to-day testosterone levels, lower risk of erythrocytosis, and potentially lower cardiovascular risk, according to the Endocrine Society 2

Intramuscular testosterone injections require intramuscular injection, which may be a disadvantage for some patients, as mentioned by the American Gastroenterological Association guidelines 2
Intramuscular testosterone injections can cause fluctuating serum testosterone levels with peaks and valleys, according to the American Gastroenterological Association guidelines 2
Potentially greater risk of cardiovascular events compared to gel formulations with intramuscular testosterone injections, as warned by the American Gastroenterological Association guidelines and the FDA 2
FDA requires labeling to inform about possible increased risk of heart attack and stroke with testosterone use, including intramuscular injections, as reported by the American Gastroenterological Association guidelines 2
Higher testosterone doses may correlate with a greater risk of elevated hematocrit, and higher testosterone levels may increase PSA levels, with the FDA requiring labeling to inform about possible increased risk of heart attack and stroke with testosterone use 2, 3
Testosterone gel has risks, including transfer risk to partners or children and variable absorption, according to the Endocrine Society 2

Testosterone levels should be checked 2-3 months after treatment initiation or after any dose adjustment, with monitoring every 6-12 months typically sufficient once stable levels are confirmed, as recommended by the American Urological Association and the Endocrine Society 1, 2
Discontinuation criteria include stopping therapy if patients do not experience symptomatic relief after reaching target testosterone levels, as recommended by the American Urological Association and the Endocrine Society 1, 2
Regular monitoring for patients on testosterone replacement therapy should include testosterone levels, hematocrit/hemoglobin, PSA levels, and cardiovascular symptoms, to detect potential risks such as erythrocytosis and cardiovascular concerns, as recommended by the American Urological Association and the Endocrine Society 1, 2

Lifestyle factors such as weight loss and physical activity can enhance endogenous testosterone production and should be encouraged alongside replacement therapy, as recommended by the American Urological Association 1

Transdermal patches (2-6 mg daily) are an alternative option for patients who may not tolerate or prefer not to use intramuscular injections, as mentioned by the American Gastroenterological Association guidelines 2
Testosterone patches are an alternative transdermal option, though skin irritation is common, as noted by the American Gastroenterological Association 2
Transdermal testosterone gel preparations are available, with typical dosing ranges of 20.25-81 mg daily, according to the Endocrine Society 2
Injectable testosterone formulations are generally more cost-effective than transdermal options, according to the American Gastroenterological Association 2