HCG

Human chorionic gonadotropin (HCG) is a 37 kDa glycoprotein consisting of a non-covalently bound alpha and beta subunit. The alpha subunit is shared with FSH, LH, and TSH; the beta subunit is HCG-specific and carries a unique 24-amino-acid C-terminal extension rich in O-linked sialic acid, which accounts for its dramatically extended half-life (~36 hours) compared to LH (~25-30 minutes). HCG binds the same receptor as LH (LHCGR), a G-protein-coupled receptor expressed on Leydig cells in the testes and on granulosa and luteal cells in the ovaries. In males, it drives intratesticular testosterone production via the StAR-CYP11A1 steroidogenic pathway; in females, it sustains corpus luteum progesterone secretion and is the signal of early pregnancy. These pharmacological properties are the basis for three FDA-approved clinical indications: prepubertal cryptorchidism, male hypogonadotropic hypogonadism, and ovulation induction or ART triggering in women. Beyond FDA-labeled uses, HCG is widely used off-label in men undergoing testosterone replacement therapy (TRT) to preserve intratesticular testosterone and spermatogenesis, and in post-cycle therapy (PCT) after anabolic steroid use. Evidence for TRT co-administration is moderate (cohort studies); evidence for PCT efficacy is anecdotal with no RCTs. WADA prohibits HCG in male athletes at all times under the S2 Prohibited List category (Peptide Hormones, Growth Factors). This entry is for research and educational reference only.