What is the recommended dosage and administration of androgen therapy, specifically testosterone, for adult males with hypogonadism?

Androgen Therapy for Adult Male Hypogonadism: Dosage and Administration

For adult males with confirmed hypogonadism, initiate testosterone replacement therapy with transdermal testosterone gel 1.62% at 40.5 mg daily (2 pump actuations) applied to shoulders and upper arms, or intramuscular testosterone cypionate/enanthate 50-400 mg every 2-4 weeks, with dose titration targeting serum testosterone levels between 350-750 ng/dL. 1, 2, 3

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm hypogonadism with two separate fasting morning total testosterone measurements below 300 ng/dL along with clinical symptoms of androgen deficiency 1, 4. The diagnosis requires both biochemical evidence and symptomatic presentation—testosterone levels alone are insufficient 4.

For men with obesity or borderline results, measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) levels for more accurate assessment 1.

First-Line Treatment: Transdermal Testosterone

Transdermal preparations are recommended as first-line therapy for men without fertility concerns 1:

• Starting dose: Testosterone gel 1.62% at 40.5 mg daily (2 pump actuations) 2
• Application site: Clean, dry, intact skin of shoulders and upper arms only—never abdomen, genitals, chest, armpits, or knees 2
• Dose range: Adjustable from 20.25 mg (1 pump) to 81 mg (4 pumps) daily 2
• Target levels: 350-750 ng/dL 2, 4

Dose Titration Protocol

Check pre-dose morning serum testosterone at 14 days and 28 days after starting treatment, then periodically thereafter 2:

• If testosterone >750 ng/dL: Decrease by 20.25 mg (1 pump actuation) 2
• If testosterone 350-750 ng/dL: Continue current dose 2
• If testosterone <350 ng/dL: Increase by 20.25 mg (1 pump actuation) 2

Transdermal testosterone demonstrates the most neutral lipid effects and avoids the fluctuating levels seen with injections 5, 6.

Alternative: Intramuscular Testosterone

For men who prefer injections or have issues with transdermal absorption 1, 3:

• Testosterone cypionate or enanthate: 50-400 mg intramuscularly every 2-4 weeks 3
• Common regimen: 200 mg every 2 weeks or 300 mg every 3 weeks 7
• Administration: Deep gluteal intramuscular injection only—never intravenous 3

While effective, intramuscular preparations cause fluctuating testosterone levels that may result in mood and sexual function variability in some men 6. However, they remain a practical and inexpensive option 8.

Special Consideration: Fertility Preservation

Exogenous testosterone is absolutely contraindicated in men desiring fertility because it suppresses spermatogenesis and causes oligospermia or azoospermia 1.

For hypogonadal men with fertility concerns:

• Use human chorionic gonadotropin (hCG) at 500-2500 IU, 2-3 times weekly, to stimulate endogenous testosterone production while preserving fertility 1, 8
• Clomiphene citrate represents another option for secondary hypogonadism 1

Monitoring Requirements

Establish a systematic monitoring protocol 1, 9:

• Baseline: Testosterone level (×2), hematocrit, PSA, lipid profile 1
• Follow-up testosterone: At 14 and 28 days, then every 3-6 months 2, 5
• Hematocrit: Monitor more closely than lipids, as polycythemia is the most common adverse effect 5
• PSA and prostate examination: Periodically in men over 40 years 1
• Lipid panel: Recheck at 3-6 months to confirm no worsening 5

Absolute Contraindications

Do not initiate testosterone therapy in men with 1:

• Active or treated breast cancer
• Severe uncontrolled heart failure
• Desire for fertility in the near term (use hCG instead)

Safety Profile

Recent high-quality evidence from the 2023 TRAVERSE trial demonstrates that testosterone therapy does not increase stroke risk in men aged 45-80 years with confirmed hypogonadism 4. The trial enrolled 5,246 men with two fasting testosterone levels <300 ng/dL and followed them for a mean of 21.7 months using transdermal 1.62% testosterone gel 4.

Testosterone replacement at physiologic doses shows neutral effects on lipid profiles, with no significant changes in triglycerides, LDL, or HDL cholesterol 5. This contrasts with supraphysiologic doses or oral nonaromatizable androgens, which adversely affect lipids 5.

Critical Safety Warning for Transdermal Products

Children must avoid contact with unwashed or unclothed application sites due to risk of virilization from secondary exposure 2. Patients must strictly adhere to application instructions and wash hands immediately after use 2.

Expected Benefits

When appropriately prescribed, testosterone replacement therapy improves 1, 4:

• Sexual function and libido
• Sense of well-being and depressive symptoms
• Lean body mass with decreased body fat
• Bone mineral density
• Insulin sensitivity in men with metabolic syndrome

The benefits are most pronounced in men with severely reduced testosterone levels (<8 nmol/L or ~230 ng/dL) 9. Effects on quality of life and erectile function remain inconsistent across studies 4.