What is the recommended treatment plan for a male with primary hypogonadism?

Testosterone Replacement Plan for Primary Hypogonadism

For men with confirmed primary hypogonadism, initiate transdermal testosterone gel 1.62% at 40.5 mg daily (2 pump actuations) applied to shoulders and upper arms as first-line therapy, with dose titration based on serum testosterone levels at 14 and 28 days. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

• Obtain two separate morning (8-10 AM) total testosterone measurements demonstrating levels below 300 ng/dL 2, 4, 3
• Measure LH and FSH levels to confirm primary hypogonadism - both will be elevated (hypergonadotropic hypogonadism) in primary testicular failure 1, 4
• Assess baseline hematocrit/hemoglobin and PSA (if age >40 years) before initiating therapy 5
• Screen for absolute contraindications: active or treated breast cancer, desire for immediate fertility 1, 5, 2

First-Line Treatment: Transdermal Testosterone

Transdermal preparations are preferred over injectable formulations because they provide stable day-to-day testosterone levels, avoid injection discomfort, and have lower risk of erythrocytosis 1, 2, 4

Dosing Protocol for Testosterone Gel 1.62%

• Starting dose: 40.5 mg testosterone (2 pump actuations or one 40.5 mg packet) applied once daily in the morning 3
• Application site: shoulders and upper arms only - do NOT apply to abdomen, genitals, chest, armpits, or knees 3
• Target testosterone range: 350-750 ng/dL 1, 2

Dose Titration Schedule

Check pre-dose morning testosterone at 14 days and 28 days after starting treatment: 3

• If testosterone >750 ng/dL: Decrease by 20.25 mg (1 pump actuation) 3
• If testosterone 350-750 ng/dL: Continue current dose 3
• If testosterone <350 ng/dL: Increase by 20.25 mg (1 pump actuation) 3
• Dose range: 20.25 mg (minimum) to 81 mg (maximum, 4 pump actuations) 3

Critical Safety Instructions for Transdermal Therapy

• Wash hands immediately with soap and water after application 3
• Cover application sites with clothing after gel dries to prevent secondary exposure 3
• Wash application site thoroughly before any anticipated skin-to-skin contact with women or children 3
• Children must avoid contact with unwashed or unclothed application sites - secondary exposure can cause virilization 3

Alternative: Injectable Testosterone (Second-Line)

If cost is prohibitive or patient prefers less frequent administration, use intramuscular testosterone cypionate or enanthate 200 mg every 2 weeks OR 300 mg every 3 weeks 2, 6, 7

Injectable Testosterone Considerations

• More economical - annual cost approximately $156 versus $2,135 for transdermal 4
• Higher risk of erythrocytosis compared to transdermal preparations 4
• Causes fluctuating testosterone levels - peaks at 2-5 days, returns to baseline at 10-14 days post-injection 4
• Measure testosterone midway between injections, targeting 500-600 ng/dL 2, 4

Monitoring Protocol

Initial Phase (First 3 Months)

• Testosterone levels at 14 days and 28 days for dose titration 3
• Assess sexual symptoms at 3 months 1
• Check hematocrit at 3 months to detect early erythrocytosis 5, 2

Maintenance Phase

• Testosterone levels every 6-12 months once stable 4
• Hematocrit monitoring periodically - higher frequency with injectable formulations 5, 2
• PSA monitoring in men >40 years 5
• Lipid profile assessment 2

Absolute Contraindications

Do NOT initiate testosterone therapy if: 1, 5, 2

• Active or previously treated breast cancer - testosterone and its conversion to estradiol can stimulate tumor growth 1, 5
• Desire for fertility - exogenous testosterone suppresses spermatogenesis and the HPG axis, causing oligospermia or azoospermia 1, 5, 2
• Pregnancy in female partners - risk of virilization from secondary exposure 3

Expected Benefits

Patients should expect: 1, 2, 4

• Improved sexual function and libido - small to moderate effect sizes 1, 2
• Enhanced sense of well-being and quality of life 1, 2
• Increased lean body mass and decreased body fat 2, 4
• Improved bone mineral density 2
• Improvements in fasting glucose, insulin resistance, triglycerides, and HDL cholesterol (especially in men with obesity) 4

Limited or no benefit for: 1, 4

• Physical functioning or muscle strength 1
• Depressive symptoms 1, 4
• Energy/vitality 1
• Cognitive function 1

Critical Pitfall: Fertility Preservation

If the patient has ANY future fertility concerns, testosterone therapy is absolutely contraindicated. 1, 5, 2 For primary hypogonadism patients, testosterone is the only option - unlike secondary hypogonadism where gonadotropins can preserve fertility, primary testicular failure cannot be overcome with gonadotropin therapy. 1 Counsel patients that testosterone will suppress remaining spermatogenesis and may cause permanent infertility. 1, 2

Lifestyle Modifications as Adjunct

In men with obesity-associated components: 1

• Weight loss through low-calorie diet can modestly improve testosterone levels (1-2 nmol/L increase) 1
• Regular physical activity provides similar modest benefits 1
• Combining lifestyle modifications with testosterone therapy yields better outcomes than either alone 1