HCG
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FDA-approved glycoprotein hormone that mimics luteinizing hormone (LH), stimulating Leydig cells to produce testosterone while preserving testicular function and fertility.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | Human Chorionic Gonadotropin, hCG, Pregnyl, Novarel, Ovidrel (recombinant) |
| Category | Sexual Health / Hormonal / Fertility |
| Sequence | Glycoprotein heterodimer (alpha + beta subunits); alpha subunit shared with LH, FSH, TSH |
| Molecular Weight | ~36,700 Da |
| Molecular Formula | Glycoprotein (not a simple peptide) |
| PubChem CID | N/A (biological macromolecule) |
| Administration | SubQ / IM |
| Typical Dose Range | 250-5000 IU per injection |
| Half-Life | ~24-36 hours |
| Storage | Lyophilized: 2-8C; Reconstituted: 2-8C for up to 30 days |
| FDA Status | Approved (multiple indications: female infertility, male hypogonadism, cryptorchidism) |
| WADA Status | Prohibited S2 (Peptide Hormones) in males |
Mechanism of Action
HCG is a naturally occurring glycoprotein hormone produced primarily by the placenta during pregnancy. It shares structural homology with luteinizing hormone (LH) — both bind the LH/CG receptor (LHCGR) on Leydig cells in the testes and theca cells in the ovaries. This receptor binding activates adenylyl cyclase, increases intracellular cAMP, and stimulates steroidogenesis.
In males, HCG directly stimulates Leydig cells to produce testosterone, bypassing the hypothalamic-pituitary axis. This is critically important during testosterone replacement therapy (TRT), where exogenous testosterone suppresses endogenous LH via negative feedback, leading to testicular atrophy and azoospermia. By providing LH-like stimulation, HCG maintains intratesticular testosterone (ITT) at levels sufficient for spermatogenesis (PMID: 15713727). Low-dose HCG (250 IU EOD) can maintain ~93% of baseline ITT even during TRT.
In females, HCG is used to trigger ovulation by mimicking the LH surge, and to support the corpus luteum during early pregnancy in assisted reproduction cycles.
Key Research Areas
- Fertility preservation during TRT — Maintaining intratesticular testosterone and spermatogenesis in men on testosterone therapy (PMID: 15713727, 23260550)
- Spermatogenesis recovery — Restoring sperm production after testosterone-induced azoospermia (PMID: 25904023)
- Hypogonadism treatment — Monotherapy alternative to TRT that preserves fertility (PMID: 29772111)
- Cryptorchidism — FDA-approved for undescended testes in prepubertal boys
- Female fertility — Ovulation induction and luteal phase support in IVF/IUI cycles
- Weight loss (controversial) — "HCG diet" claims lack scientific support and are considered fraudulent by FDA
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 3 | ITT maintenance, clomiphene comparison, muscle strength |
| Human observational | 3 | Spermatogenesis preservation, recovery, monotherapy safety |
| Animal in vivo | Multiple | Extensive historical literature on gonadal function |
| In vitro | Multiple | Receptor binding, steroidogenesis studies |
| Systematic reviews | 1+ | Meta-analyses of HCG in cryptorchidism |
Clinical Applications
- Sexual Health — Testosterone optimization and testicular function support
- Fertility — Fertility preservation during TRT; spermatogenesis recovery
- Erectile Dysfunction — Secondary benefit via testosterone restoration
- Libido Enhancement — Via testosterone optimization
Protocols Using This Peptide
- Sexual Health Protocol
- GH Optimization Protocol (as adjunct for HPG axis support)
Ageless Peps Products
- AP-HCG-Vial — HCG 5000 IU Vial
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| SubQ/IM | 250 IU | Every other day | Ongoing with TRT | PMID 15713727 (ITT maintenance) |
| SubQ/IM | 500 IU | 3x/week | Ongoing with TRT | PMID 23260550 (fertility preservation) |
| SubQ/IM | 1000-3000 IU | 3x/week | 3-6 months | PMID 25904023 (spermatogenesis recovery) |
| SubQ/IM | 5000 IU | 3x/week | Variable | PMID 29772111 (hypogonadism monotherapy) |
Cycling
HCG is typically used continuously alongside TRT rather than cycled. For fertility recovery protocols, treatment duration is 6-12 months until spermatogenesis is restored. Some practitioners cycle HCG (e.g., 6 weeks on / 2 weeks off) to prevent Leydig cell desensitization, though evidence for this practice is limited. High-dose protocols (>3000 IU 3x/week) may cause desensitization and should be time-limited.
Contraindications & Safety
- Contraindications: Prostate cancer (androgen-sensitive), precocious puberty, androgen-dependent tumors, HCG-secreting tumors
- Common side effects: Injection site pain/swelling, headache, fatigue, mood changes, gynecomastia (via aromatization of increased testosterone to estradiol)
- Drug interactions: May potentiate effects of testosterone; estradiol monitoring recommended when combined with TRT
- Pregnancy/nursing: Category X in pregnancy (for males using HCG; different context for female fertility use)
- Special populations: Monitor estradiol levels — HCG increases both testosterone and estradiol. Aromatase inhibitor may be needed in men with high aromatase activity. Leydig cell desensitization possible with prolonged high-dose use.
Synergistic Combinations
- Gonadorelin + HCG — Dual HPG axis support; GnRH pulsatile + direct Leydig cell stimulation
- PT-141 + HCG — Testosterone optimization (HCG) + central libido enhancement (PT-141)
- Kisspeptin-10 + HCG — Upstream GnRH activation + direct gonadal stimulation
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| PMID-15713727 – Low-Dose HCG Maintains Intratesticular Testosterone | Low-dose HCG maintains ITT in men with T-induced gonadotropin suppression | 2005 | RCT |
| PMID-23260550 – HCG Preserves Spermatogenesis During TRT | Concomitant HCG preserves spermatogenesis during TRT | 2013 | Observational |
| PMID-25904023 – HCG-Based Combination Therapy Spermatogenesis Recovery | HCG-based combination therapy for spermatogenesis recovery | 2015 | Case Series |
| PMID-29772111 – Clomiphene and HCG Both Effective in Hypogonadism | Clomiphene and HCG both effective in restoring testosterone | 2018 | RCT |
| PMID-30159241 – HCG Indications for Infertility in Hypogonadal Men | Indications for HCG for infertility management | 2018 | Narrative Review |
References
- PMID 15713727 — Coviello et al., JCEM 2005 (ITT dose-response)
- PMID 23260550 — Hsieh et al., J Urol 2013 (spermatogenesis preservation)
- PMID 25904023 — Wenker et al., J Sex Med 2015 (fertility recovery)
- PMID 29772111 — Dabaja et al., BJU Int 2018 (HCG vs clomiphene RCT)
- PMID 30159241 — Lee & Ramasamy, Transl Androl Urol 2018 (clinical review)
Related
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