Pregnyl Dosing for Adult Male Hypogonadism
For adult men with hypogonadotropic (secondary) hypogonadism who desire fertility preservation, start Pregnyl (human chorionic gonadotropin) at 500–2,500 IU subcutaneously or intramuscularly 2–3 times weekly. 1, 2 If fertility is not a concern, testosterone replacement therapy is preferred over hCG monotherapy. 1
FDA-Approved Dosing Regimens
The FDA label for Pregnyl provides two specific regimens for hypogonadotropic hypogonadism in males 2:
- Standard regimen: 500–1,000 IU three times weekly for 3 weeks, followed by the same dose twice weekly for an additional 3 weeks 2
- Extended regimen: 4,000 IU three times weekly for 6–9 months, then reduce to 2,000 IU three times weekly for an additional 3 months 2
Evidence-Based Starting Dose
Begin with 1,500 IU intramuscularly or subcutaneously twice weekly as the most commonly studied and effective starting dose. 1, 3, 4 This regimen has been validated in multiple clinical studies and produces physiologic testosterone levels while preserving spermatogenesis. 3, 4
Route of Administration
Subcutaneous administration is equally effective as intramuscular injection and is strongly preferred because it allows self-administration, improves patient acceptance, and produces comparable serum testosterone levels. 3, 5 Pharmacokinetic studies demonstrate that subcutaneous hCG 1,500 IU twice weekly generates cumulative testosterone concentrations equivalent to intramuscular dosing. 3
When to Add FSH
If sperm counts remain low or azoospermia persists after 3–6 months of hCG monotherapy, add recombinant FSH 75–150 IU subcutaneously 2–3 times weekly. 1, 6 Combined hCG plus FSH therapy produces superior fertility outcomes compared to hCG alone in men with secondary hypogonadism. 1, 6
Monitoring Protocol
- Initial phase (first 3 months): Measure serum testosterone at 14 and 28 days after starting therapy to confirm normalization before adding FSH if needed 1
- Ongoing surveillance: Check testosterone levels every 6–12 months once stable 1
- Fertility assessment: Obtain semen analysis at 3–4 months if fertility is the goal 4, 6
Expected Outcomes
- Testosterone normalization: hCG 1,500 IU twice weekly restores serum testosterone to mid-normal range (450–600 ng/dL) in most men with secondary hypogonadism 3, 4
- Spermatogenesis: Approximately 60–70% of men achieve detectable sperm counts with hCG monotherapy; this increases to >80% when FSH is added 4, 6
- Time to response: Testosterone levels normalize within 2–4 weeks; spermatogenesis typically requires 6–12 months of treatment 4, 6
Critical Contraindications
Never use Pregnyl in men with primary (testicular) hypogonadism (elevated LH/FSH with low testosterone), as the testes cannot respond to gonadotropin stimulation. 1 These patients require testosterone replacement therapy instead. 1
Common Pitfalls to Avoid
- Do not use hCG for men who do not desire fertility unless testosterone replacement is contraindicated; transdermal testosterone gel is first-line for hypogonadism without fertility concerns 1
- Do not start with the high-dose FDA regimen (4,000 IU three times weekly) as initial therapy; this dose is excessive and increases the risk of supraphysiologic testosterone levels and side effects 2, 7
- Do not delay adding FSH beyond 6 months if sperm counts remain inadequate on hCG monotherapy, as combined therapy is required for optimal spermatogenesis in most men 1, 6
Recombinant vs. Urinary hCG
Both recombinant (rhCG) and urinary (uhCG) formulations produce equivalent testosterone responses and have similar pharmacokinetics (half-life ≈5.8 days). 7 If using recombinant hCG (Ovidrel pen), the starting dose is 62.5 µg (6 clicks) subcutaneously twice weekly, which is bioequivalent to 1,500 IU of urinary hCG. 7