hCG

A dimeric glycoprotein hormone that activates the LH/hCG receptor to drive gonadal steroidogenesis, licensed as an injectable prescription biologic for cryptorchidism, male hypogonadotropic hypogonadism, and ovulation induction.

Also referenced as: HCG, Human Chorionic Gonadotropin, Chorionic Gonadotropin, Choriogonadotropin Alfa, Pregnyl, Novarel, Ovidrel

What is hCG?

Human chorionic gonadotropin is a heterodimeric glycoprotein hormone built from a common alpha subunit — shared with LH, FSH, and TSH — and a hormone-specific beta subunit, held together non-covalently and heavily glycosylated. It is produced by placental syncytiotrophoblast during pregnancy; pharmaceutical material is either purified from the urine of pregnant women or produced recombinantly as choriogonadotropin alfa.

At roughly 36–40 kDa it is far larger than the synthetic peptides that dominate research catalogs, and it is not synthesized by solid-phase chemistry. It appears in the research-compound market chiefly for its LH-like action on the testis, which is the basis for its off-label use alongside exogenous androgens, and because U.S. compounded supply narrowed sharply after a 2020 regulatory reclassification.

How it works

• LH/hCG receptor agonism — hCG binds the lutropin/choriogonadotropin receptor (LHCGR), a class A G protein–coupled receptor on testicular Leydig cells and ovarian theca and granulosa cells, coupling primarily to Gs and raising cAMP to drive steroidogenesis (Ascoli et al., Endocrine Reviews, 2002, 23(2):141–174)
• Cystine-knot heterodimer — each subunit adopts a cystine-knot fold, and the beta subunit wraps a “seat belt” segment around the alpha subunit; only the assembled alpha/beta dimer is bioactive, and isolated subunits do not activate the receptor (Lapthorn et al., Nature, 1994, 369(6480):455–461; Pierce & Parsons, Annual Review of Biochemistry, 1981, 50:465–495)
• A C-terminal extension that matters in vivo, not in vitro — the O-glycosylated carboxyl-terminal extension unique to the hCG beta subunit is dispensable for receptor binding and in vitro signaling, but truncating it made hCG roughly 3-fold less active in a rat ovulation assay (Matzuk et al., Endocrinology, 1990, 126(1):376–383). The reason is pharmacokinetic: that same peptide sustains the prolonged plasma half-life of the hCG dimer, and grafting it onto FSH lengthens FSH’s half-life and in vivo potency (Fares et al., PNAS, 1992, 89(10):4304–4308)
• Intratesticular testosterone maintenance — in 29 men with normal reproductive physiology whose gonadotropins were suppressed by weekly testosterone enanthate, co-administered hCG maintained intratesticular testosterone dose-dependently over 3 weeks: post-treatment ITT was 25% below baseline at 125 IU every other day, 7% below at 250 IU, and 26% above at 500 IU, against a 94% collapse on testosterone plus placebo (Coviello et al., Journal of Clinical Endocrinology & Metabolism, 2005, 90(5):2595–2602)

Research status

hCG is a licensed U.S. prescription biologic with decades of labeled use, but the evidence base is unevenly distributed: strong for reproductive endocrinology, thin for the uses that drive gray-market interest, and explicitly negative for weight loss.

Approved indications. Urinary-derived chorionic gonadotropin for injection (marketed as Pregnyl and Novarel; FDA’s application records show initial U.S. approvals of January 15, 1974 for Novarel and October 20, 1976 for Pregnyl) is indicated for prepubertal cryptorchidism not due to anatomic obstruction, selected cases of hypogonadotropic hypogonadism in males, and induction of ovulation and pregnancy in anovulatory infertile women whose anovulation is secondary rather than due to primary ovarian failure — in that last setting given after menotropin pretreatment. The recombinant analog choriogonadotropin alfa (Ovidrel) was approved September 20, 2000 to trigger final follicular maturation in assisted reproduction.

Fertility preservation alongside testosterone (off-label). Hsieh et al. retrospectively reviewed 26 hypogonadal men on testosterone replacement with concomitant hCG at 500 IU intramuscularly every other day, and reported no significant change in semen parameters and no cases of azoospermia over a mean 6.2 months of follow-up (The Journal of Urology, 2013, 189(2):647–650). This is a small uncontrolled series, and Coviello et al. (2005) was a 3-week study in men with normal reproductive physiology using a surrogate endpoint, not a fertility outcome. No large randomized trial has tested this combination for fertility outcomes.

hCG monotherapy in symptomatic men. Two retrospective single-center reports from the same University of Miami group cover different populations, and are often conflated. Zucker et al. reviewed 31 men with hypogonadal symptoms but testosterone above 300 ng/dL, reporting subjective improvement in erectile dysfunction (19/22) and libido (20/25) with no change in hematocrit, PSA, or HbA1c (Cureus, 2022, 14(5):e25543). Rainer et al. reviewed a separate cohort of 28 men with prior exogenous testosterone use who were switched to hCG monotherapy, reporting no significant change in mean hormone levels, a small decrease in hematocrit, and no thromboembolic events (Cureus, 2022, 14(6):e25826). Both lack control arms and randomization, and neither was designed to measure long-term efficacy.

Weight loss — a documented failure. Stein et al. ran a 32-day randomized, double-blind trial in 51 women and found no significant difference between hCG and placebo in weight loss, percent weight loss, hip or waist circumference, or hunger ratings (The American Journal of Clinical Nutrition, 1976, 29(9):940–948). Lijesen et al. later applied a criteria-based meta-analysis to eight controlled and 16 uncontrolled trials of the Simeons protocol, found most to be of poor methodological quality, and concluded there is no scientific evidence that hCG causes weight loss, redistributes fat, suppresses hunger, or induces well-being (British Journal of Clinical Pharmacology, 1995, 40(3):237–243). The approved product labeling carries an explicit all-capitals statement that hCG has not been demonstrated to be effective adjunctive therapy in the treatment of obesity, and that there is no substantial evidence it increases weight loss beyond that resulting from caloric restriction.

Trial registry picture. ClinicalTrials.gov lists roughly 409 studies naming chorionic gonadotropin as an intervention (August 2026), and they are overwhelmingly reproductive: about 211 under infertility and 47 under ovulation induction, against 23 under hypogonadism and 6 under obesity. Late-phase hypogonadism work does exist — a dozen Phase 3/4 records — but it sits squarely inside the labeled indication, testing spermatogenesis induction in congenital or isolated hypogonadotropic hypogonadism, often hCG combined with FSH or corifollitropin alfa. What the registry does not contain is a late-phase program for the two uses that actually drive research-market demand: hCG as an adjunct to exogenous testosterone, and hCG monotherapy for symptoms in men with normal testosterone.

Common dosage forms

• Prescription injectable — lyophilized powder in a multi-dose vial, packaged with a separate diluent vial of bacteriostatic water and reconstituted before intramuscular use. Licensed vial strengths include both 5,000 and 10,000 USP units; Pregnyl is supplied as 10,000 units per vial, and Novarel is currently marketed in 5,000 and 10,000 unit presentations.
• Recombinant prefilled syringe — choriogonadotropin alfa supplied as a single-dose subcutaneous prefilled syringe delivering 250 mcg (0.25 mg/0.5 mL), a mass-based rather than IU-based presentation. The original lyophilized-vial form has been discontinued.
• Research-market vials — lyophilized powder labeled 5,000 IU or 10,000 IU, sometimes bundled with bacteriostatic water. These match the licensed strengths, so the number on the label distinguishes nothing on its own; what differs is the absence of a licensed manufacturer, a diluent of known composition, and release testing. Potency is stated in IU rather than milligrams, a different measurement basis than the mass-and-purity figures used for synthetic peptides.
• Oral and sublingual “hCG drops” — a separate consumer product class marketed for weight loss, typically homeopathic-labeled dilutions rather than the injectable prescription drug.

Key considerations

• Regulatory reclassification changed access. On March 23, 2020, chorionic gonadotropin transitioned from an approved NDA to a deemed biologics license application under the BPCI Act; Pregnyl and Novarel both appear on FDA’s transition list, and Drugs@FDA now shows them as BLA 017692 and BLA 017016. Because the 503A and 503B compounding exemptions do not extend to licensed biologics, compounded hCG lost its clear legal pathway and supply contracted sharply rather than vanishing outright. Borgert et al. contacted the 81 FDA-registered 503B outsourcing facilities and got 75 responses: only 5 still supplied hCG, 8 had supplied it previously, and 6 of those 8 cited the 2020 mandate as the reason they stopped (Sexual Medicine, 2023, 11(2):qfad004). This supply contraction, not new efficacy data, explains much of the recent gray-market visibility.
• The weight-loss claim is affirmatively disproven, not merely unproven. Randomized and meta-analytic evidence is negative, and on December 6, 2011 the FDA and FTC issued seven joint warning letters to marketers of over-the-counter “homeopathic” hCG weight-loss products, which are unapproved new drugs. There is no FDA-approved hCG product for weight loss.
• Purity documentation does not establish potency here. hCG bioactivity depends on correct subunit assembly and glycosylation, and the compendial standard is expressed in International Units determined by bioassay. A mass-purity certificate of the kind issued for small synthetic peptides does not demonstrate that a given hCG vial has the labeled biological activity.
• Naming confusions are common. Intact dimeric hCG (the hormone) is distinct from free beta-hCG (the subunit measured by pregnancy tests and tracked as a tumor marker); choriogonadotropin alfa is the recombinant version of the same hormone, not a different molecule, but it is dosed by mass rather than in IU. Products sold as “hCG drops” are a different regulatory and pharmacological category entirely.
• Labeled safety signals are non-trivial. Approved labeling describes ovarian hyperstimulation syndrome with potential for rapid progression, arterial thromboembolic events, and multiple births in roughly 20% of pregnancies resulting from treatment; precocious puberty in pediatric use, with instruction to discontinue if signs appear; and hypersensitivity reactions. In men, raising endogenous testosterone also raises substrate for aromatization, so estradiol-related effects are a foreseeable consequence of the mechanism.