What is the typical dosing of Human Chorionic Gonadotropin (HCG) for men on Testosterone Replacement Therapy (TRT)?

HCG Dosing for Men on Testosterone Replacement Therapy

Primary Recommendation

For men on TRT who wish to preserve fertility, the recommended HCG dosage is 500 IU administered subcutaneously or intramuscularly every other day (equivalent to 3 times weekly), based on the most robust clinical evidence. 1, 2

Dosing Protocols

Standard Fertility Preservation Regimen

• 500 IU subcutaneously or intramuscularly every other day is the most well-validated protocol 2
• Alternative dosing: 500-1,000 IU administered 2-3 times weekly 1
• Both subcutaneous and intramuscular routes produce comparable testosterone levels, though subcutaneous is better tolerated and can be self-administered 3

Evidence Supporting This Dose

• A retrospective study of 26 hypogonadal men demonstrated that 500 IU HCG every other day maintained normal semen parameters during concurrent TRT over 6+ months of follow-up 2
• No patients became azoospermic on this regimen, and 9 of 26 men achieved pregnancy with their partners during treatment 2
• Lower doses (125-250 IU every other day) maintain intratesticular testosterone at 75-93% of baseline levels, which may be sufficient for some men 4

Mechanism and Rationale

• Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis, reducing LH and FSH secretion 4
• This leads to decreased intratesticular testosterone (ITT), which is critical for spermatogenesis 4, 5
• TRT alone causes oligospermia or azoospermia in up to 40% of patients 1, 2
• HCG mimics LH action, directly stimulating Leydig cells to produce ITT and maintain spermatogenesis 4, 5

Dose-Response Relationship

The evidence demonstrates a clear dose-dependent effect on intratesticular testosterone:

• 15 IU every other day: Minimal ITT stimulation 5
• 60 IU every other day: Modest ITT increase 5
• 125 IU every other day: ITT maintained at ~75% of baseline 4
• 250 IU every other day: ITT maintained at ~93% of baseline 4
• 500 IU every other day: ITT maintained at or above baseline levels 4, 2

Alternative Dosing Regimens

Higher Dose Protocols (from FDA labeling)

• 500-1,000 IU three times weekly for 3 weeks, followed by same dose twice weekly for 3 weeks for hypogonadotropic hypogonadism 6
• 4,000 IU three times weekly for 6-9 months, then reduced to 2,000 IU three times weekly for 3 months 6

Important caveat: These higher FDA-approved doses are for men NOT on concurrent TRT and are intended as monotherapy for hypogonadotropic hypogonadism 6. When combined with TRT, lower doses (500 IU every other day) are sufficient and preferred 2.

Weekly Dosing

• 250 μg weekly (approximately 6,500 IU) showed benefit in oligozoospermic men, though this was not combined with TRT 7
• This higher weekly dose is excessive for fertility preservation during TRT and may increase side effects 7

Monitoring Parameters

• Baseline assessment: Semen analysis, serum testosterone, LH, FSH, estradiol 2
• Follow-up semen analysis: Every 3 months to assess response 7
• Serum testosterone and estradiol: Monitor to ensure adequate testosterone levels without excessive aromatization 2
• Clinical response: Assess for testicular size maintenance and fertility outcomes 2

Critical Considerations

When HCG May Not Be Appropriate

• Men with hypogonadotropic hypogonadism seeking fertility should receive gonadotropin therapy (HCG with or without FSH) as primary treatment rather than TRT 1
• If fertility is desired in the near future, consider gonadotropin monotherapy instead of TRT plus HCG 1

Recovery After TRT Discontinuation

• If TRT must be stopped to restore fertility, spermatogenesis recovery may take months to years 1
• Concurrent HCG use during TRT prevents this prolonged recovery period 2

Route of Administration

• Subcutaneous administration is preferred over intramuscular due to better patient acceptance, ability to self-administer, and comparable efficacy 3
• Both routes produce similar cumulative testosterone levels 3

Common Pitfalls to Avoid

• Using doses that are too low (<250 IU every other day) may not adequately maintain intratesticular testosterone for optimal spermatogenesis 4
• Using doses that are too high (>1,000 IU every other day) provides no additional benefit and increases cost and potential side effects 4, 5
• Failing to monitor semen parameters during treatment, as individual response varies 2, 7
• Assuming all men on TRT need HCG: Only men concerned about fertility preservation require concurrent HCG 1, 2