HCG
Human Chorionic Gonadotropin (hCG) is a glycoprotein hormone consisting of 237 amino acids (alpha and beta subunits) that mimics luteinizing hormone, stimulating testosterone production in males and supporting corpus luteum function in females. It is used clinically in fertility treatment, hypogonadism management, and post-cycle therapy.
Human Chorionic Gonadotropin (hCG) is a glycoprotein hormone naturally produced by trophoblast cells of the placenta during pregnancy. It functions as a luteinizing hormone (LH) analog, binding to the same LH/CG receptor on gonadal tissue to stimulate steroidogenesis.
Overview
hCG is composed of two non-covalently linked subunits: an alpha subunit shared with LH, FSH, and TSH, and a unique beta subunit that confers receptor specificity. The beta subunit of hCG shares approximately 85% sequence homology with LH-beta but contains a C-terminal extension of 24 amino acids with four additional O-linked glycosylation sites, which accounts for its significantly longer half-life compared to LH (~24-36 hours vs. ~20 minutes).
hCG is produced primarily during pregnancy, where it maintains the corpus luteum and supports early progesterone production. Outside of pregnancy, it is used therapeutically as an LH surrogate due to its longer half-life and identical receptor binding. Recombinant hCG (choriogonadotropin alfa) and urinary-derived preparations are both available clinically.
Mechanism of Action
Human Chorionic Gonadotropin (HCG) functions as a potent analog of luteinizing hormone (LH) due to its structural similarity. It binds with high affinity to the LH/Chorionic Gonadotropin Receptor (LHCGR), a G-protein-coupled receptor expressed on Leydig cells in the testes and theca/luteal cells in the ovaries. Receptor activation stimulates the Gs alpha subunit, which activates adenylyl cyclase, increasing intracellular cyclic AMP (cAMP) levels and subsequently activating protein kinase A (PKA).
PKA phosphorylation targets are central to steroidogenesis. The most critical is the Steroidogenic Acute Regulatory (StAR) protein, which mediates cholesterol transport from the outer to inner mitochondrial membrane -- the rate-limiting step in all steroid hormone production. PKA also upregulates CYP11A1 (cholesterol side-chain cleavage enzyme), which converts cholesterol to pregnenolone, the precursor for all steroid hormones. In males, this cascade drives testosterone synthesis in Leydig cells, maintaining intratesticular testosterone levels essential for spermatogenesis and supporting Sertoli cell function.
In females, HCG mimics the mid-cycle LH surge to trigger final oocyte maturation and ovulation in assisted reproductive technology. During early pregnancy, placental HCG maintains the corpus luteum, ensuring continued progesterone production to sustain the endometrium until the placenta assumes this role. HCG's longer half-life compared to LH (due to its unique beta subunit) allows for more sustained receptor stimulation, making it therapeutically valuable for fertility support and maintaining testicular function during testosterone replacement therapy.
Reconstitution Calculator
HCG
Human Chorionic Gonadotropin (hCG) is a glycoprotein hormone naturally produced
Set up a clean workspace with all supplies ready.
4x / week for weeks
Research
Male Hypogonadism & TRT Support
hCG is frequently co-administered with exogenous testosterone to maintain intratesticular testosterone (ITT) levels and preserve spermatogenesis during testosterone replacement therapy (TRT). Coviello et al. (2008) demonstrated that low-dose hCG (250 IU every other day) co-administered with testosterone enanthate maintained ITT within the normal range, whereas testosterone alone reduced ITT by 94%. This finding established hCG as a critical adjunct for men on TRT who wish to preserve fertility. Higher doses (500 IU every other day) produced supraphysiological ITT levels without additional clinical benefit.
Post-Cycle Therapy
In the context of anabolic steroid use, hCG is employed during post-cycle therapy (PCT) to accelerate recovery of the hypothalamic-pituitary-gonadal (HPG) axis. By directly stimulating Leydig cells, hCG can restore testosterone production independently of pituitary LH secretion, which remains suppressed following exogenous androgen use. Research suggests that hCG administration during or immediately after steroid cycles prevents Leydig cell desensitization and testicular atrophy, facilitating faster endogenous recovery. Protocols typically use 1000-2000 IU every other day for 2-3 weeks, often combined with selective estrogen receptor modulators (SERMs).
Female Fertility & Ovulation Induction
hCG serves as a surrogate LH surge in assisted reproductive technology (ART). In IVF protocols, a single injection of 5,000-10,000 IU urinary hCG or 250 mcg recombinant hCG (choriogonadotropin alfa) triggers final oocyte maturation approximately 36 hours before egg retrieval. Trinchard-Lugan et al. (2002) characterized the pharmacokinetics of recombinant hCG, demonstrating predictable absorption and a terminal half-life of approximately 29 hours following subcutaneous administration, supporting standardized ovulation trigger protocols.
Weight Loss Controversy (HCG Diet)
The so-called "hCG diet," combining hCG injections with severe caloric restriction (500 kcal/day), was popularized by Simeons in the 1950s. However, multiple controlled trials have conclusively demonstrated that hCG provides no additional weight loss benefit beyond caloric restriction alone. The FDA, AMA, and multiple regulatory bodies have declared hCG ineffective for weight loss. A meta-analysis of randomized controlled trials found no statistically significant difference in weight loss, hunger reduction, or body composition between hCG and placebo groups when caloric intake was controlled. The observed weight loss is attributable entirely to the very-low-calorie diet component.
Cryptorchidism
hCG is used as first-line pharmacological therapy for cryptorchidism (undescended testes) in prepubertal boys. By stimulating testosterone production locally, hCG can promote testicular descent in cases where the testes are positioned in the inguinal canal. Treatment typically involves 500-1500 IU administered twice weekly for 3-5 weeks. Success rates range from 10-50% depending on testicular position and patient age, with higher success for testes closer to the scrotum. Surgical orchiopexy remains the definitive treatment when hormonal therapy fails.
Tumor Marker
The beta subunit of hCG serves as a critical tumor marker for gestational trophoblastic disease, testicular germ cell tumors, and certain extragonadal malignancies. Stenman et al. (2006) reviewed the diagnostic utility of hCG and its variants (free beta-hCG, hyperglycosylated hCG, nicked hCG) in oncology, establishing guidelines for their use in diagnosis, staging, and treatment monitoring.
Safety Profile
hCG is generally well-tolerated when used at recommended doses, but carries several notable risks:
- Ovarian hyperstimulation syndrome (OHSS): The most serious adverse effect in women, particularly during IVF. hCG triggers VEGF release from granulosa cells, increasing vascular permeability. Severe OHSS can cause ascites, pleural effusion, thromboembolic events, and in rare cases, death. Risk is highest in women with polycystic ovary syndrome or high antral follicle counts
- Gynecomastia: In males, hCG-stimulated testosterone is partially aromatized to estradiol, which can cause breast tissue development. Aromatase inhibitors are sometimes co-administered to mitigate this effect
- Headache and injection site reactions: Common mild adverse effects including pain, swelling, and erythema at injection sites
- Multiple pregnancy: When used for ovulation induction, hCG increases risk of multiple gestation
- Leydig cell desensitization: Prolonged high-dose hCG can downregulate LHCGR expression and paradoxically reduce testosterone production
- Antibody formation: Rare development of neutralizing antibodies against hCG, reducing efficacy with chronic use
Pharmacokinetic Profile
HCG — Pharmacokinetic Curve
Subcutaneous injection, Intramuscular injectionQuick Start
- Typical Dose
- 250-1500 IU (lower for TRT adjunct, higher for fertility)
- Frequency
- 2-3 times weekly, or every other day for lower doses
- Route
- Subcutaneous injection, Intramuscular injection
- Cycle Length
- Ongoing with TRT or 3-6 months for fertility protocols
- Storage
- Lyophilized: Room temperature. Reconstituted: 2-8°C, use within 30-60 days
Molecular Structure
- Formula
- Glycoprotein (variable glycosylation)
- Weight
- 36 Da
- Length
- 237 amino acids
- CAS
- 9002-61-3
- PubChem CID
- 4369448
- Exact Mass
- 321.0995 Da
- LogP
- -4.1
- TPSA
- 160 Ų
- H-Bond Donors
- 6
- H-Bond Acceptors
- 8
- Rotatable Bonds
- 10
- Complexity
- 403
Identifiers (SMILES, InChI)
InChI=1S/C11H19N3O6S/c12-6(11(19)20)2-1-3-8(15)14-7(5-21)10(18)13-4-9(16)17/h6-7,21H,1-5,12H2,(H,13,18)(H,14,15)(H,16,17)(H,19,20)/t6-,7-/m0/s1
XFOOPZIJVVDYHI-BQBZGAKWSA-NResearch Indications
Male Fertility
Maintains intratesticular testosterone at baseline during testosterone therapy, preventing atrophy and preserving fertility.
FDA-approved for secondary hypogonadism; combined with FSH for spermatogenesis induction.
Restores testicular function after anabolic steroid cycles.
Female Fertility
FDA-approved trigger for follicular maturation; 15-25% pregnancy rate per cycle.
Pediatric
FDA-approved for prepubertal undescended testes not due to anatomical obstruction; ~25% success rate.
Research Protocols
subcutaneous Injection
Human chorionic gonadotropin. 3x weekly subcutaneous protocol.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| Standard maintenance | 500 IU | 3x weekly (Mon/Wed/Fri) | 12 weeks |
| High-dose recovery — Phase 1 | 1,500 IU | 3x weekly | Weeks 1-4 |
| High-dose recovery — Phase 2 | 2,000 IU | 3x weekly | Weeks 5-8 |
| High-dose recovery — Phase 3 | 1,000 IU | 3x weekly | Weeks 9-12(Cycle 8-12 weeks. Severe suppression 16+ weeks.) |
Reconstitution Guide (5000mg vial + 2mL BAC water)
- Wipe vial tops with alcohol swab
- Draw 2.0 mL bacteriostatic water into syringe
- Inject slowly down the inside wall of the peptide vial
- Gently swirl to dissolve — never shake
- Resulting concentration: 2,500 IU/mL
- For 500 IU dose: draw 20 units (0.20 mL)
- For 1,000 IU dose: draw 40 units (0.40 mL)
- For 1,500 IU dose: draw 60 units (0.60 mL)
- For 2,000 IU dose: draw 80 units (0.80 mL)
- Store reconstituted vial refrigerated at 2-8°C
Interactions
Peptide Interactions
Commonly combined in TRT to maintain testicular function and preserve fertility.
Complementary mechanisms for HPG axis stimulation.
What to Expect
What to Expect
Cellular-level action begins; no immediate noticeable effects
Testosterone increase detectable on labs; possible mood/energy improvement
Testicular fullness/size improvement noticeable; improved well-being
Stable testosterone levels; fertility parameters beginning to improve
Sperm count improvements if used for fertility; sustained testicular function
Maintained testicular size and function with ongoing use
Safety Profile
Common Side Effects
- Gynecomastia (breast tenderness/swelling) due to increased estrogen
- Headaches, irritability, and mood swings (especially initially)
- Fluid retention and edema
- Potential antibody formation with long-term use
Contraindications
- Hormone-sensitive cancers (prostate, breast)
- Pregnancy (except as prescribed)
- Precocious puberty risk in children
Discontinue If
- Signs of gynecomastia (breast tenderness, swelling, nipple sensitivity)
- Severe or persistent headaches
- Signs of blood clots (leg swelling/pain, shortness of breath, chest pain)
- Allergic reactions (rash, hives, difficulty breathing, facial swelling)
- Severe abdominal pain or bloating in women (possible OHSS)
- Testicular pain or swelling beyond normal
- Significant mood changes (depression, aggression, severe irritability)
- Vision changes
Quality Indicators
What to look for
- White to off-white lyophilized powder or cake in sealed vial
- Completely clear solution after reconstitution
- Proper labeling: Pregnyl, Novarel (urinary), Ovidrel (recombinant)
- Clear expiration and lot number
- Cold chain compliance (recombinant requires refrigeration throughout)
Caution
- Generic/compounding pharmacy products - quality varies
- Ensure compounding pharmacy is accredited
Red flags
- Cloudiness, discoloration, or floating particles indicates degradation
- Compromised vial seal or expired product
Frequently Asked Questions
References (26)
- [3]Spermatogenesis Induction with HCG/FSH (2018)
- [5]Ovulation Induction Success Rates (2017)
- [4]Cryptorchidism Treatment Meta-Analysis (Cochrane) (2014)
- [7]
- [1]HCG for Intratesticular Testosterone Maintenance (2005)
- [2]HCG Monotherapy for Hypogonadism (2013)
- [10]European Association of Urology. Guidelines on Paediatric Urology: Cryptorchidism. (2023)
- [13]
- [14]
- [15]
- [16]HCG for Hypogonadism: Updated AUA Guidelines (2024)
- [22]Simeons ATW. "The action of chorionic gonadotrophin in the obese." *Lancet*. 1954;264 :946-947 Lancet (6845)
- [24]Hsieh et al — Low-dose hCG maintains spermatogenesis in men receiving testosterone therapy: a systematic review Andrology (2023)
- [25]Luo et al — Efficacy and safety of hCG for male hypogonadotropic hypogonadism: a meta-analysis Front Endocrinol (2022)
- [26]
- [27]Barbonetti et al — Low-dose human chorionic gonadotropin for fertility preservation during testosterone replacement therapy Expert Opin Drug Saf (2022)
- [1]Coviello AD et al. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab (2005)
- [3]Trinchard-Lugan I et al. Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers. Reprod Biomed Online (2002)
- [5]
- [6]Depenbusch M et al. Maintenance of spermatogenesis in hypogonadotropic hypogonadal men with human chorionic gonadotropin alone. Eur J Endocrinol (2002)
- [8]Lijesen GK et al. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis. Br J Clin Pharmacol (1995)
- [11]Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome. Fertil Steril (2016)
- [12]
- [4]
- [2]Coviello AD et al. Concurrent human chorionic gonadotropin maintains intratesticular testosterone in a man receiving a gonadotropin-releasing hormone agonist. J Clin Endocrinol Metab (2008)
- [9]Roche DJ. hCG treatment for cryptorchidism. Horm Res (1988)
GV1001
GV1001 is a 16-amino acid peptide derived from the active site of human telomerase reverse transcriptase (hTERT 611-626) developed as a cancer vaccine and repurposed for Alzheimer's disease, with demonstrated anti-inflammatory, neuroprotective, and cell-penetrating properties independent of its immunogenic function.
Hexapeptide-11
Hexapeptide-11 is a yeast-derived peptide from Saccharomyces cerevisiae that stimulates keratinocyte renewal and cell cycle progression, researched for improving skin surface quality and turnover rate in cosmetic applications.