Testosterone Replacement Therapy Guidelines

Introduction to Testosterone Replacement Therapy

The American College of Physicians recommends starting testosterone replacement therapy with testosterone enanthate or cypionate 100-200 mg intramuscularly every 2 weeks, or preferably 50-100 mg weekly for more stable levels 1
The Endocrine Society suggests that weekly administration of 50-100 mg provides significantly more stable testosterone levels compared to biweekly dosing 1
The New England Journal of Medicine notes that peak serum levels occur 2-5 days after injection and often return to baseline by 10-14 days, creating problematic fluctuations in mood and sexual function 2

The American Urological Association recommends testosterone enanthate or cypionate as a starting dose of 100-200 mg intramuscularly every 2 weeks 1
The European Association of Urology suggests a preferred alternative of 50-100 mg weekly for more stable testosterone levels with less fluctuation 1
The American College of Physicians notes that testosterone undecanoate (long-acting) has an initial dose of 750 mg intramuscularly, with a second dose at 4 weeks and maintenance of 750 mg every 10 weeks thereafter 1

The American Association of Clinical Endocrinologists recommends testosterone gel 1% (AndroGel) with a starting dose of 50-100 mg daily 1
The New England Journal of Medicine notes that testosterone patches (Androderm) have a starting dose of 2-6 mg per 24 hours, but have a major limitation of skin reactions occurring in up to 66% of users 2

The Endocrine Society recommends measuring testosterone levels at 14 days and 28 days after starting treatment or any dose adjustment, and targeting mid-normal values 1
The American College of Physicians suggests monitoring every 3-6 months for the first year, then yearly thereafter 2
The European Association of Urology notes that the target testosterone levels should be in the mid- to upper-normal range (approximately 450-600 ng/dL) to optimize treatment response 2

The American Urological Association recommends confirming diagnosis by measuring serum testosterone in the morning on at least two separate days, with both values below normal range 2
The American College of Physicians suggests baseline assessments including PSA and digital rectal examination, hematocrit or hemoglobin, voiding symptoms, history of sleep apnea, and lipid evaluation (optional) 2

The American Association of Clinical Endocrinologists notes that injectable formulations have advantages of being relatively inexpensive and having flexible dosing intervals, but disadvantages of requiring intramuscular injection and having fluctuating serum testosterone levels 1
The New England Journal of Medicine suggests that transdermal gel preparations have advantages of easy application, good skin tolerability, and more stable testosterone levels, but disadvantages of potential transfer to partners or children and higher cost 2

The Endocrine Society recommends monitoring hematocrit levels and considering temporarily withholding therapy, reducing dosage, or performing phlebotomy if hematocrit rises above reference range 2
The American College of Physicians notes that prostate monitoring is mandatory, with digital rectal examination and PSA measurement at each monitoring visit 2
The European Association of Urology suggests advising patients that fertility will be greatly compromised during testosterone replacement therapy due to down-regulation of gonadotropins 2