What is the recommended Human Chorionic Gonadotropin (HCG) dosing regimen for Hormone Replacement Therapy (HRT) to maintain fertility in patients?

HCG Dosing for Fertility Preservation During Hormone Replacement Therapy

For men on testosterone replacement therapy (TRT) who wish to maintain fertility, administer HCG 500-1,000 IU intramuscularly 2-3 times weekly concurrently with TRT. 1

Primary Dosing Protocol

The standard approach for fertility preservation during TRT involves:

• HCG 500 IU administered every other day (or 500-1,000 IU given 2-3 times weekly) via intramuscular injection 1, 2
• This dosing mimics luteinizing hormone (LH) action on testicular Leydig cells, maintaining intratesticular testosterone levels necessary for spermatogenesis 1
• The 500 IU every-other-day regimen has been specifically validated to preserve semen parameters in men on TRT, with no patients becoming azoospermic during combined therapy 2

Mechanism and Rationale

• Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis, reducing gonadotropin secretion and causing oligospermia or azoospermia in up to 40% of patients on TRT alone 1
• HCG directly stimulates testicular Leydig cells to produce intratesticular testosterone, bypassing the suppressed pituitary axis 1
• This maintains the high local testosterone concentrations within the testes required for ongoing sperm production 1

Enhanced Protocol for Optimal Results

For men with more severe hypogonadotropic hypogonadism or those requiring fertility restoration:

• Consider HCG 3,000 IU plus FSH 75 IU administered three times weekly 3
• This combination protocol demonstrated 74% improvement in sperm concentrations in men with previous testosterone use 3
• The addition of FSH to HCG provides optimal outcomes for fertility preservation according to European guidelines 1
• Alternative dosing for hypogonadotropic hypogonadism ranges from 500-2,500 IU administered 2-3 times weekly 4

Critical Clinical Considerations

Concurrent TRT does not impede HCG-mediated fertility preservation:

• Men can continue testosterone therapy while receiving HCG without compromising spermatogenic recovery (74% improvement with or without concurrent testosterone) 3
• This contradicts older concerns and allows men to maintain symptom control while preserving fertility 3

Expected outcomes with HCG monotherapy during TRT:

• Semen parameters remain stable over 1+ year of follow-up 2
• Pregnancy rates of approximately 35% (9 of 26 men) achieved during combined TRT/HCG therapy 2
• No difference in outcomes between injectable testosterone versus transdermal gel formulations 2

Alternative Approach for Men Not Yet on TRT

For men with hypogonadotropic hypogonadism planning fertility in the near future who are not yet on TRT:

• Gonadotropin therapy alone (HCG with or without FSH) is preferable to starting TRT 1
• This is the standard treatment recommended by the European Association of Urology for men with hypogonadotropic hypogonadism seeking fertility 1
• Combined HCG and FSH therapy for 12-24 months promotes testicular growth in nearly all patients, spermatogenesis in approximately 80%, and pregnancy rates around 50% 5

Important Caveats and Pitfalls

Timing matters for fertility recovery:

• If TRT must be discontinued to restore fertility without HCG, recovery of spermatogenesis may take months to years 1
• Starting HCG concurrently with TRT from the outset is far superior to attempting restoration later 1

Monitoring requirements:

• Monitor serum testosterone response before considering addition of FSH 4
• Assess semen parameters every 3 months during therapy 6
• Higher BMI (28 kg/m²) may predict better response compared to lower BMI (25 kg/m²) 6

Side effects:

• Gynecomastia is the most common adverse effect due to HCG-stimulated aromatase activity increasing estradiol secretion 5
• No serious adverse events reported in clinical studies 7, 2