How can injectable testosterone (Testosterone) in combination with human chorionic gonadotropin (hCG) help a man in his mid 40s?

Injectable Testosterone Combined with hCG for Men in Their Mid-40s

For men in their mid-40s with testosterone deficiency, combining injectable testosterone with hCG is primarily indicated when fertility preservation is a priority, as this combination maintains spermatogenesis while restoring testosterone levels—otherwise, testosterone monotherapy alone is appropriate for those not concerned with fertility. 1, 2

Primary Clinical Scenarios

For Men Interested in Fertility Preservation

Testosterone monotherapy should never be prescribed to men interested in current or future fertility, as it suppresses spermatogenesis and can lead to azoospermia in 40% of patients. 1, 3

The combination approach works through distinct mechanisms:

• Injectable testosterone restores systemic testosterone levels and addresses hypogonadal symptoms 4
• hCG (500-2500 IU, 2-3 times weekly) stimulates testicular Leydig cells to maintain intratesticular testosterone production, which is essential for ongoing sperm production 2, 3

Research demonstrates that low-dose hCG (500 IU every other day) successfully maintains semen parameters in men on testosterone replacement, with 95.9% maintaining or recovering spermatogenesis and documented pregnancies occurring in partners during treatment 3, 5

For Men with Hypogonadotropic Hypogonadism

hCG is the first-line treatment for males with hypogonadotropic hypogonadism who need testosterone restoration while preserving fertility potential. 2

In this population, hCG alone may be sufficient without exogenous testosterone, as it directly stimulates endogenous testosterone production 1, 2

Expected Clinical Benefits

Symptom Improvements with Testosterone Therapy

Men in their mid-40s can expect the following benefits from testosterone treatment:

• Sexual function: Small to moderate improvements in erectile function and global sexual function 1
• Energy and vitality: Modest improvements in fatigue and energy levels 1
• Body composition: Improvements in lean body mass and anemia 1
• Bone health: Enhanced bone mineral density 1
• Mood: Small improvements in depressive symptoms, though most benefit is seen in those with baseline depression 1

Physical function improvements are minimal based on objective measures like walk tests 1

Additional Benefits of hCG Combination

When hCG is added to testosterone therapy:

• Fertility preservation: Spermatogenesis is maintained throughout treatment 3, 5
• Testicular size maintenance: Prevents testicular atrophy that occurs with testosterone monotherapy 4, 3
• Symptom improvement: In men with normal testosterone (>300 ng/dL) but hypogonadal symptoms, hCG monotherapy improved erectile dysfunction in 86% and libido in 80% 6

Critical Pre-Treatment Requirements for Men Over 40

Before initiating therapy, the following assessments are mandatory:

Baseline testing required: 1

• PSA measurement to exclude occult prostate cancer (two measurements if first is elevated)
• Hemoglobin/hematocrit (withhold if Hct >50% until investigated)
• Cardiovascular risk factor assessment (dyslipidemia, hypertension, diabetes, smoking)

Fertility assessment if relevant: 1

• Testicular examination for size, consistency, and descent
• Serum FSH measurement
• Consider semen analysis if FSH is elevated

Safety Considerations

Monitoring Requirements

During treatment, hematocrit >54% warrants intervention such as dose reduction or temporary discontinuation, as injectable testosterone causes the greatest increases in hemoglobin/hematocrit among all formulations. 1

Cardiovascular Safety

Low-certainty evidence shows a small increase to no difference in adverse cardiovascular events with testosterone therapy 1

Observational studies with follow-up ranging from 0.73 to 10.3 years showed no increased risk for mortality, cardiovascular events, or thromboembolic events 1

hCG monotherapy showed no thromboembolic events in treated patients 6

Long-Term Fertility Implications

Men must understand that the time to recover spermatogenesis after testosterone cessation is highly variable, potentially taking months or rarely years. 1

However, when hCG is used concomitantly with testosterone from the outset, this recovery period is avoided as spermatogenesis is maintained throughout treatment 3, 5

Practical Implementation

The typical regimen combines:

• Injectable testosterone: Weekly intramuscular injections (dose titrated to achieve mid-normal range levels of 350-600 ng/dL) 1, 3
• hCG: 500 IU intramuscularly every other day, or 500-2500 IU 2-3 times weekly 2, 3
• Optional aromatase inhibitor (anastrozole): May be added to manage estradiol levels if needed 4

Recovery of testosterone levels and symptom improvement typically occurs within 4-6 months, with return of spermatogenesis averaging 4.6 months when recovering from prior testosterone-only therapy 5

Common Pitfalls to Avoid

• Never prescribe testosterone alone to men who may want fertility in the future—the suppression of spermatogenesis can be prolonged and unpredictable 1, 2
• Do not overlook PSA screening in men over 40—two elevated values require formal evaluation before initiating therapy 1
• Monitor hematocrit closely with injectable testosterone—this formulation has the highest risk of polycythemia 1
• Avoid testosterone therapy in men with hematocrit >50% at baseline until the etiology is investigated 1