A tier · strong
An FDA-approved hormone with decades of randomized fertility and endocrine data behind its three narrow labelled indications, held below S because effect sizes in its best-studied use are modest and its most popular off-label use is explicitly repudiated on its own label.
hcg
hCG is a placental glycoprotein hormone that acts at the LH receptor and is FDA-approved for prepubertal cryptorchidism, selected hypogonadotropic hypogonadism in males, and ovulation induction in anovulatory women. The randomized evidence supporting these uses is real but the measured effect in cryptorchidism is modest, and the label explicitly states hCG has not been shown effective for obesity.
the explanation
hCG is a pregnancy hormone that tells the ovaries or testes to do what luteinising hormone normally tells them to do. It is a genuinely approved medicine for a few specific fertility and hormone problems, but its famous use in weight-loss clinics is contradicted by the drug's own FDA label.
regulatory status
FDA-approved prescription drug; WADA-prohibited in males
Approved (e.g. Pregnyl, NDA 017692) for prepubertal cryptorchidism not due to anatomical obstruction, selected cases of hypogonadotropic hypogonadism in males, and induction of ovulation and pregnancy in anovulatory women. The label carries the capitalised statement that 'HCG HAS NOT BEEN DEMONSTRATED TO BE EFFECTIVE ADJUNCTIVE THERAPY IN THE TREATMENT OF OBESITY' and 'HAS NO KNOWN EFFECT ON FAT MOBILIZATION, APPETITE OR SENSE OF HUNGER, OR BODY FAT DISTRIBUTION.' The WADA 2026 Prohibited List names chorionic gonadotrophin (CG) among testosterone-stimulating peptides prohibited in males.
how it works · proposed mechanism
hCG is a long-acting agonist at the luteinising hormone/choriogonadotropin receptor, substituting for endogenous LH in both gonads.
LHCG receptor agonism
hCG binds the same G-protein-coupled receptor as luteinising hormone, raising intracellular cAMP in ovarian theca and granulosa cells and in testicular Leydig cells. Because it is exogenous, it acts independently of pituitary output.
Sialylation extends exposure
The hCG beta subunit carries a C-terminal peptide with heavy sialic-acid glycosylation that slows hepatic clearance. The result is a far longer receptor-occupancy window than a native LH pulse produces.
Gonadal steroid output
Sustained LHCG receptor signalling drives Leydig-cell testosterone synthesis in males and triggers final oocyte maturation and corpus luteum formation in females. This is the basis of both its cryptorchidism and its ART trigger indications.
what’s reported
evidence shape
5 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The strongest randomized signal for hCG is in a paediatric indication where the absolute success rate is under one in five, and pooled trials cannot separate true descent from retractile testes. Its enormous consumer popularity rests on a weight-loss claim that its own FDA label rejects in capital letters.
key published findings
- Human trial (meta-analysis): Pyorala, Huttunen and Uhari pooled 33 trials covering 3,282 boys and 4,524 undescended testes; across the 11 randomized controlled trials (872 boys, 1,174 testes) hCG achieved testicular descent in 19% (95% CI 13-25%) versus 4% (95% CI 2-6%) for placebo.
- Human pharmacokinetics: the Ovidrel FDA label reports a mean terminal half-life of approximately 29 +/- 6 hours after subcutaneous recombinant hCG, with mean absolute bioavailability of about 40%.
- Human structural data: the FDA label describes the molecule as two non-covalently linked subunits of 92 and 145 amino acid residues, with the alpha subunit essentially identical to that of pituitary LH and FSH.
- Regulatory finding: the Pregnyl label states in capitals that hCG has not been demonstrated to be effective adjunctive therapy in the treatment of obesity and has no known effect on fat mobilisation, appetite, or body fat distribution.
- Anti-doping finding: the WADA 2026 Prohibited List classifies chorionic gonadotrophin among testosterone-stimulating peptides prohibited in males at all times, in and out of competition.
limitations of the evidence
- The cryptorchidism meta-analysis is now three decades old and its reviewers cautioned that hormonal therapy should not be used for impalpable testes, where surgery is the alternative.
- Pooled cryptorchidism trials cannot reliably distinguish genuine descent from repositioning of retractile testes, which inflates apparent success.
- The hypogonadotropic hypogonadism indication is described on the label as 'selected cases' and rests on far smaller and less controlled datasets than the fertility indications.
documented safety signals
- Ovarian Hyperstimulation Syndrome: the label describes OHSS as a medical event distinct from uncomplicated ovarian enlargement that 'may progress rapidly to become a serious medical event', with sudden ovarian enlargement, ascites, and pleural effusion.
- Precocious puberty: the label warns that induction of androgen secretion by hCG may induce precocious puberty in paediatric patients treated for cryptorchidism, and directs that therapy be discontinued if signs occur.
- Thromboembolism and arterial thromboembolic events are listed label risks, as is multi-fetal gestation.
- Labelled adverse reactions include headache, irritability, restlessness, depression, fatigue, oedema, precocious puberty, gynaecomastia, and injection-site pain; localised and systemic hypersensitivity reactions including anaphylaxis have been reported.
- Contraindicated in prior hypersensitivity to gonadotropins, high serum FSH indicating primary gonadal failure, uncontrolled non-gonadal endocrinopathies, and tumours of the hypothalamus, pituitary, ovary, breast, uterus, or prostate.
- The Pregnyl diluent contains benzyl alcohol as preservative, which the label states in capitals is NOT FOR USE IN NEWBORNS.
- Prohibited in male athletes under WADA S2; use is an anti-doping rule violation and is also detectable as an atypical steroid-profile marker.
identity
| full name | Human Chorionic Gonadotropin |
| category | Hormonal |
| modality | protein hormone |
| cas | 9002-61-3 |
| half-life | Recombinant choriogonadotropin alfa: mean terminal half-life approximately 29 +/- 6 hours after subcutaneous administration, with absolute bioavailability around 40% (Ovidrel FDA label). Urinary-derived hCG half-life is not stated in the Pregnyl label. |
| sequence | Heterodimer: alpha subunit (92 aa, shared with LH/FSH/TSH) non-covalently paired with a hCG-specific beta subunit (145 aa); heavily glycosylated. Not a linear synthetic peptide. |
laboratory handling
| storage | Store unopened vials at controlled room temperature 15-30 C (59-86 F). Reconstituted solution is stable for 60 days when refrigerated at 2-8 C; do not freeze. Protect from light. |
| solubility | Supplied as a lyophilised powder reconstituted with the supplied bacteriostatic aqueous diluent; freely water-soluble as a glycoprotein. |
| co-studied with | In published fertility protocols hCG is used alongside FSH-containing gonadotropins such as menotropins, where it supplies the LH-like maturation trigger. This index does not describe regimens; note only that WADA prohibits hCG in males and that co-administration with other gonadotropins raises the documented OHSS and multiple-gestation risks described on both labels. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedU.S. Food and Drug Administration · 2023 · official
U.S. Food and Drug Administration · 2010 · official
World Anti-Doping Agency · 2026 · official
Journal of Clinical Endocrinology and Metabolism 80(9):2795-2799; DARE structured abstract · 1995 · review
Pediatric Surgery International · 2004 · review
others in Hormonal