What is the appropriate dosing regimen, administration technique, and monitoring for intramuscular testosterone therapy in an adult male diagnosed with hypogonadism?

Testosterone Injection Therapy for Hypogonadism

Diagnostic Requirements Before Initiating Therapy

You must confirm biochemical hypogonadism with two separate fasting morning total testosterone measurements (8–10 AM) both < 300 ng/dL, plus the presence of specific symptoms—primarily diminished libido and erectile dysfunction—before starting any testosterone therapy. 1

• Measure serum LH and FSH after confirming low testosterone to distinguish primary (elevated LH/FSH) from secondary (low or low-normal LH/FSH) hypogonadism, as this distinction is critical for treatment selection and fertility counseling 1, 2
• In men with borderline total testosterone (231–346 ng/dL) or obesity, measure free testosterone by equilibrium dialysis and SHBG to differentiate true from functional hypogonadism 1, 2
• Obtain baseline hematocrit/hemoglobin (absolute contraindication if > 54%), PSA in men > 40 years (PSA > 4.0 ng/mL requires urologic evaluation), fasting glucose, and lipid profile before initiating therapy 1, 2

Recommended Dosing Regimen

Start with 50–100 mg of intramuscular testosterone cypionate or enanthate weekly, or 100–200 mg every 2 weeks, with weekly dosing strongly preferred because it provides more stable serum levels and reduces the supraphysiologic peaks and subtherapeutic troughs seen with biweekly administration. 3, 4

• The FDA-approved dosing range is 50–400 mg every 2–4 weeks, but weekly dosing (50–100 mg) produces superior pharmacokinetic stability 3, 4
• For patients starting with very low testosterone (< 150 ng/dL), begin at 100 mg weekly and titrate based on response 3
• Doses above 400 mg per month are rarely required due to the prolonged action of these preparations 4

Administration Technique

Inject deeply into the gluteal muscle using proper intramuscular technique, avoiding intravascular injection; use of a wet needle or syringe may cause cloudiness but does not affect potency. 4

• Inspect the solution visually before administration—testosterone enanthate should be clear, colorless to pale yellow 4
• Follow standard precautions for intramuscular administration to minimize injection-site reactions 4

Monitoring Protocol

Measure testosterone levels 2–3 months after initiation, then every 3–6 months during the first year, and annually thereafter once stable; draw blood midway between injections (days 5–7 for weekly dosing, days 7–10 for biweekly dosing) targeting mid-normal values of 500–600 ng/dL. 1, 5, 3, 2

Initial Follow-Up (2–3 Months)

• Check total testosterone (timed midway between injections), hematocrit, and PSA 1, 3
• Assess clinical response—particularly sexual function and libido—and adjust dose in 25–50 mg increments if symptoms persist with suboptimal levels 3

Ongoing Monitoring (Every 3–6 Months First Year, Then Annually)

• Repeat total testosterone, hematocrit/hemoglobin, PSA, and lipid profile 1, 3, 2
• Perform digital rectal examination at each visit 1
• Withhold treatment immediately if hematocrit exceeds 54% and consider therapeutic phlebotomy in high-risk patients 1, 5, 2
• Refer to urology if PSA rises > 1.0 ng/mL within the first 6 months or > 0.4 ng/mL per year thereafter 1

Expected Treatment Outcomes

Testosterone therapy produces small but significant improvements in sexual function and libido (standardized mean difference 0.35), but little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition. 1

• Improvements in sexual symptoms typically appear within 3–6 months of achieving target testosterone levels 1
• Modest favorable changes in metabolic parameters (insulin resistance, triglycerides, HDL cholesterol) may occur 1
• Discontinue therapy at 12 months if there is no documented improvement in sexual function, as continued treatment without benefit exposes the patient to unnecessary risks 1

Absolute Contraindications

Never initiate testosterone therapy in men with: 1, 5, 2

• Active desire for fertility preservation (testosterone causes prolonged, potentially irreversible azoospermia; use gonadotropin therapy instead)
• Active or treated male breast cancer
• Prostate cancer or PSA > 4.0 ng/mL without negative biopsy
• Hematocrit > 54%
• Untreated severe obstructive sleep apnea
• Myocardial infarction or stroke within the past 3–6 months
• Uncontrolled heart failure

Critical Pitfalls to Avoid

• Do not diagnose hypogonadism on a single testosterone measurement or symptoms alone—require two morning values < 300 ng/dL plus specific sexual symptoms 1
• Do not use biweekly dosing if the patient experiences mood fluctuations or symptom recurrence before the next injection—switch to weekly administration 3
• Do not continue full-dose testosterone when hematocrit exceeds 54%—this is an absolute indication to withhold therapy 1, 5
• Do not prescribe testosterone for fatigue, low energy, weight loss, or athletic performance—these are not evidence-based indications and show minimal to no benefit even with confirmed hypogonadism 1
• Injectable testosterone carries a higher risk of erythrocytosis (≈ 44%) compared to transdermal preparations (≈ 15%)—consider switching formulations if erythrocytosis develops 1