hCG (Human Chorionic Gonadotropin) for Testicular Function — Testosterone & Androgens

LH-mimetic gonadotropin that maintains testicular size, intratesticular testosterone, and fertility during TRT.

Overview

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that shares structural homology with luteinizing hormone (LH) and binds to the LH/CG receptor on Leydig cells in the testes. During testosterone replacement therapy, exogenous testosterone suppresses the HPG axis, reducing endogenous LH secretion and leading to testicular atrophy, decreased intratesticular testosterone (ITT), and impaired spermatogenesis. hCG administration maintains Leydig cell function and ITT levels, preserving testicular volume and fertility potential. Studies demonstrate that hCG 500 IU every other day maintains ITT at approximately 25% of baseline (versus near-zero without hCG) and preserves qualitative spermatogenesis in most men on TRT. hCG is FDA-approved for hypogonadism, prepubertal cryptorchidism, and is an essential component of fertility treatment protocols. Following the FDA's 2020 reclassification of hCG as a biologic, compounding pharmacy production was restricted, increasing costs and access challenges. Recombinant hCG (Ovidrel) and urinary-derived formulations (Pregnyl) remain available.

Indications

  • FDA-approved: Male hypogonadotropic hypogonadism
  • FDA-approved: Prepubertal cryptorchidism
  • FDA-approved: Ovulation induction in women (with menotropins)
  • Off-label: Testicular function preservation during TRT
  • Off-label: Fertility preservation in men on testosterone
  • Off-label: Post-cycle therapy component

Mechanism of Action

hCG binds to the LH/CG receptor on testicular Leydig cells with high affinity, mimicking the action of endogenous LH

Dosing

CompoundDoseFrequencyNotes
hCG500 IUEvery other dayStandard TRT adjunct dose for testicular preservation
hCG250 IUEvery other dayLow dose — adequate for many patients with lower aromatization
hCG1000 IUThree times weeklyFertility protocol — higher dose for spermatogenesis
hCG1500-4000 IU2-3x weekly x 6-12 weeksFDA-approved hypogonadism protocol

Evidence Grade

GRADE B

Safety & Contraindications

  • May increase estradiol significantly — monitor and manage with AI if needed
  • Injection site reactions (pain, swelling, bruising)
  • Headache and irritability reported
  • Gynecomastia risk due to estrogen elevation
  • Overstimulation of Leydig cells possible at high doses
  • Desensitization of LH receptors possible with very high or continuous dosing
  • Since 2020 FDA reclassification as biologic, compounding restricted