COMPOUND

Compounds / Ancillaries

HCG

Human Chorionic Gonadotropin (Pregnyl, Novarel)

Ancillaries SubQ · IM FDA approved

Placental glycoprotein hormone with strong LH-receptor agonism. FDA-approved (Pregnyl/Novarel, NDA 017016, 1939) for hypogonadotropic hypogonadism, prepubertal cryptorchidism, and ovulation induction. Standard off-label use in men's health: preserves testicular volume and intratesticular testosterone during exogenous TRT, and at higher doses restores spermatogenesis in hypogonadotropic men or recovers the HPTA after AAS use. SubQ has displaced IM as the community-standard route despite IM being the FDA-labeled route.

At a glance

Half-life
~36 h Biphasic: initial t½ ~11h, terminal t½ ~23-38h after IM/SubQ injection (Steier 1989, PMID 2776893; Pregnyl/Novarel label NDA 017016). Detectable in blood up to 7-10 days post-dose.
Routes
SubQ · IM
Vial sizes
10000 mg
Evidence base
4 studies 3 human · 1 review

Mechanism

Structurally similar to LH; binds the LH/CG receptor on testicular Leydig cells with high affinity, stimulating intratesticular testosterone production (50-100x serum T) and supporting the Sertoli-cell environment for spermatogenesis. In published trials of HCG co-administered during TRT-induced LH suppression, intratesticular testosterone was maintained near baseline (75-126%) and sperm production was preserved relative to TRT alone, with 0% azoospermia against significant suppression in the TRT-only group. Pooled gonadotropin trials: HCG ± FSH restored spermatogenesis in ~75% of hypogonadotropic men over 12-24 months. Biphasic PK with ~36h terminal half-life. Unlike exogenous testosterone (which suppresses LH and shrinks the testes), HCG bypasses the pituitary axis and acts directly on the testis, preserving size, intratesticular T, and fertility potential.

Dosing

Any amounts shown here are reported from published studies only. 3 of 4 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.

Where a study reports an amount, it appears in that study's entry below, attributed to the source.

Published evidence

  1. Meta-analysis 2009

    Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men

    Liu PY, Baker HW, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ J Clin Endocrinol Metab

    Pooled gonadotropin trials: HCG ± FSH restored spermatogenesis in ~75% of hypogonadotropic men over 12-24 months.

    PMID 19066302

  2. Human RCT 2005

    Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression

    Coviello AD, Matsumoto AM, Bremner WJ, et al. J Clin Endocrinol Metab

    125-500 IU HCG EOD maintained intratesticular T at 75-126% of baseline (vs 6% in placebo controls) during 200 mg/wk TE-induced LH suppression. 250 IU approximated baseline; 500 IU exceeded it by 26%.

    PMID 15713727

  3. Human RCT 1989

    Pregnancy specific beta 1-glycoprotein and human chorionic gonadotropin in maternal serum after intravenous and intramuscular administration

    Steier JA, Bergsjø P, Myking OL Br J Obstet Gynaecol

    Pharmacokinetic basis for the ~36h beta-phase half-life of injected HCG.

    PMID 2776893

  4. Human observational 2013

    Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy

    Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI J Urol

    500 IU HCG every other day during TRT preserved sperm production with 0% azoospermia vs significant suppression in TRT-only group.

    PMID 23260550

Reported side effects

Gynecomastia
Common Moderate · Direct testicular T stimulation also drives intratesticular aromatization → E2 elevation; dose-related. Mitigate by reducing dose, splitting frequency, or adding low-dose AI.
Acne
Common Mild · Secondary to elevated androgens. Per Pregnyl/Novarel label (NDA 017016).
Injection site reaction
Common Mild · Local redness/discomfort; less than oil-based injectables.
Water retention / edema
Occasional Mild · Mild fluid retention; typically transient.
Headache
Occasional Mild · Per FDA label.
Mood changes / irritability
Occasional Mild · Reported with sustained dosing. Per FDA label.
Leydig cell desensitization (chronic high-dose)
Rare Moderate · Chronic supratherapeutic HCG can downregulate LH receptors (PMID 15871908).
Allergic reaction / anaphylaxis
Rare Serious · Boxed risk of allergic response to urine-derived protein in Pregnyl/Novarel.
Ovarian hyperstimulation syndrome (females)
Rare Serious · Risk in female fertility-induction use (not relevant to male TRT-adjunct dosing).

Interactions

  • Test Cypionate Synergy

    Standard fertility + testicular-preservation adjunct. HCG mimics suppressed LH to maintain Leydig cell activity during TRT.

  • Test Enanthate Synergy

    Same adjunct relationship as cypionate: HCG preserves intratesticular T and testicular volume during TRT-induced LH suppression.

  • Anastrozole Synergy

    HCG drives intratesticular aromatization and can elevate serum E2; an AI may be needed if E2 climbs symptomatically.

  • Enclomiphene Redundant

    Both restore the endogenous T pathway via different mechanisms: enclomiphene at the pituitary, HCG at the Leydig cell. Some clinics combine for max recovery; usually one suffices.

Reconstitution and storage

10,000 IU vial + 10 mL bacteriostatic water = 1000 IU/mL → 0.25 mL = 250 IU dose. Or 5,000 IU vial + 5 mL BAC = 1000 IU/mL → same math. Brand Pregnyl ships with diluent; Novarel similar. Use BAC water (NOT sterile water) for multi-dose stability. Refrigerate post-reconstitution; use within 30 days. Do not freeze.

Lyophilized: stable at room temp until reconstituted. Reconstituted: refrigerate 2-8°C, use within 30 days, discard if cloudy.

Open the reconstitution calculator for HCG