HCG (Human Chorionic Gonadotropin)

1. Overview and Classification Caveat

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced physiologically by the syncytiotrophoblast of the developing placenta from the time of implantation. It rescues the corpus luteum of early pregnancy from luteolysis, maintains progesterone production until the fetoplacental unit becomes autonomous, and plays additional roles in immune tolerance, angiogenesis, and uterine receptivity [21][25].

A point of terminology matters at the outset: hCG is not strictly a peptide. It is a heterodimeric glycoprotein composed of two non-covalently associated subunits, an alpha chain of 92 amino acids and a beta chain of 145 amino acids, with approximately 30% of its mass contributed by N-linked and O-linked oligosaccharides [20][21][25]. Its molecular weight (approximately 36.7 kDa) and its extensive post-translational glycosylation place it firmly in the glycoprotein hormone family alongside luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH) [20]. It is included here, and on many peptide-therapeutics references, because clinicians routinely prescribe it in the same treatment algorithms as short peptides such as gonadorelin, triptorelin, and buserelin, and because it acts on the same receptor (LHCGR) as endogenous LH. Readers should, however, understand that the peptide label is a matter of clinical custom rather than biochemical accuracy.

hCG is approved by the U.S. Food and Drug Administration (FDA) for three clinical indications: (1) induction of ovulation and pregnancy in anovulatory infertile women who have been pre-treated with a follicle-stimulating agent; (2) selected cases of male hypogonadotropic hypogonadism, with or without FSH supplementation, to induce spermatogenesis and testicular androgen production; and (3) prepubertal cryptorchidism not due to anatomic obstruction [9][23]. It is approved under multiple brand names: Ovidrel (recombinant choriogonadotropin alfa, EMD Serono), Pregnyl (urinary-derived hCG, Organon), and Novarel (urinary-derived hCG, Ferring) [23].

Off-label, hCG is widely used in andrology to preserve testicular volume and spermatogenesis during testosterone replacement therapy (TRT), to restart endogenous function after anabolic-androgenic steroid (AAS) exposure, and as monotherapy in selected men with symptomatic low-normal testosterone [3][12][15][16]. It is NOT approved for weight loss, and decades of controlled evidence, culminating in sustained FDA and FTC enforcement action against homeopathic and OTC products, confirm that the Simeons diet protocol (hCG plus 500 kcal/day) produces no greater weight loss than caloric restriction alone [4][5].

Molecule class

Glycoprotein heterodimer (not strictly a peptide)

Subunits

Alpha 92 aa (shared with LH, FSH, TSH) + Beta 145 aa (CG-specific, includes C-terminal peptide)

Molecular Weight

Approximately 36.7 kDa (heavily glycosylated, ~30% carbohydrate by mass)

Receptor

LHCGR (luteinizing hormone/choriogonadotropin receptor), Gs-coupled GPCR shared with LH

Half-life

Urinary hCG approximately 37 hours terminal; recombinant hCG (choriogonadotropin alfa) approximately 36 hours after subcutaneous dosing

Routes

Intramuscular (urinary hCG), subcutaneous (r-hCG, also urinary hCG off-label)

FDA Status

Approved for ovulation induction, luteinization, male hypogonadotropic hypogonadism, and prepubertal cryptorchidism. NOT approved for weight loss.

WADA Status

Prohibited in males at all times (S2 Peptide Hormones)

2. Molecular Structure

Heterodimer Architecture

hCG is assembled from two genetically distinct polypeptide chains that associate non-covalently to form the biologically active heterodimer [20][25]:

• Alpha subunit (CGA): 92 amino acids, encoded by the single CGA gene on chromosome 6q14-q21. This subunit is shared with LH, FSH, and TSH. It contains ten cysteine residues forming five intrachain disulfide bonds, and two N-linked glycosylation sites at Asn52 and Asn78.
• Beta subunit (CGB): 145 amino acids, encoded by a cluster of CGB genes on chromosome 19q13.3 (CGB1, CGB2, CGB3/5, CGB7, CGB8). The beta subunit is unique to chorionic gonadotropin and confers biological specificity. It contains twelve cysteines forming six disulfide bonds (including a cystine knot) and carries four glycosylation sites: two N-linked (Asn13, Asn30) and two O-linked (Ser121, Ser127) on the C-terminal peptide.

Relative to LH-beta, hCG-beta has a 24-amino-acid C-terminal extension (the C-terminal peptide, CTP), residues 121-145, which carries four serine-linked mucin-type O-glycans. This CTP is unique to chorionic gonadotropin and is the principal determinant of hCG's long circulating half-life, because the sialylated O-glycans shield the molecule from hepatic clearance via the asialoglycoprotein receptor [21][25].

Glycosylation and Bioactivity

The carbohydrate content of hCG varies by source and by physiological or pathological context. Urinary hCG from early pregnancy carries highly sialylated, heterogeneous glycans; hyperglycosylated hCG (H-hCG) from the invasive cytotrophoblast has distinct O-linked core-2 structures and is believed to mediate trophoblast invasion [21]. Recombinant choriogonadotropin alfa (Ovidrel), produced in Chinese hamster ovary (CHO) cells, has a defined glycan profile with slightly different sialylation patterns from the urinary product but equivalent LHCGR binding and clinical bioactivity [17][22][23].

Desialylation in vitro dramatically accelerates clearance and abolishes in vivo bioactivity without affecting in vitro receptor binding, underscoring the pharmacokinetic role of the terminal sialic acids [21].

3. Receptor and Mechanism

LHCGR: Shared with Luteinizing Hormone

hCG binds and activates the luteinizing hormone/choriogonadotropin receptor (LHCGR), a seven-transmembrane G-protein-coupled receptor expressed on ovarian theca and granulosa cells, testicular Leydig cells, and at lower levels in uterine endometrium, corpus luteum, trophoblast, and selected extragonadal tissues [21][25]. LHCGR couples primarily to Gs, activating adenylate cyclase and raising intracellular cAMP, which drives steroidogenic acute regulatory protein (StAR) translocation and cholesterol mobilization into the inner mitochondrial membrane for conversion to pregnenolone by CYP11A1.

Although hCG and LH share the same receptor, they differ in kinetics of receptor activation: hCG binds with higher affinity and produces a more sustained cAMP response than LH at equimolar concentrations, reflecting differences in the hinge-region interactions of their beta subunits [21][25]. Clinically, this translates to hCG being substantially more potent on a molar basis and markedly longer-acting than LH, making hCG the practical pharmacologic substitute for LH in gonadotropin replacement regimens.

Cellular Effects

In ovarian granulosa and theca cells, LHCGR activation drives androgen production from theca cells (substrate for granulosa aromatization) and, after the mid-cycle LH surge, induces luteinization, ovulation, and progesterone secretion from the corpus luteum. In Leydig cells, LHCGR activation drives testosterone biosynthesis that supports intratesticular androgen concentrations 50-100-fold higher than serum, which are required for Sertoli-cell-supported spermatogenesis [2][19]. In the corpus luteum of early pregnancy, placental hCG sustains progesterone production that maintains decidual integrity [21].

Intratesticular Testosterone (ITT)

A foundational observation in male reproductive endocrinology is that spermatogenesis depends on intratesticular testosterone concentrations 50-100-fold higher than serum, which cannot be maintained by systemic testosterone replacement at any clinically acceptable dose. When exogenous testosterone suppresses LH via negative feedback, Leydig cells cease endogenous testosterone production, ITT drops to 1-2% of baseline, and spermatogenesis fails [2][19]. hCG bypasses the hypothalamic-pituitary block by directly stimulating Leydig-cell LHCGR, restoring ITT despite pituitary suppression [2]. This mechanism is the rationale for low-dose hCG co-administration during TRT to preserve fertility [3][12][15][16].

4. Pharmacokinetics

Urinary hCG (Pregnyl, Novarel)

After intramuscular injection, urinary hCG is absorbed slowly, reaching peak serum concentration at approximately 6-12 hours. Bioavailability is high (approximately 60-80%). The terminal elimination half-life is approximately 37 hours, driven by renal clearance of the intact glycoprotein [22][23]. After a 5,000 IU IM dose, serum hCG remains detectable for 10-14 days, which is clinically relevant for pregnancy-test interference following fertility treatment.

Recombinant hCG (Ovidrel, choriogonadotropin alfa)

Subcutaneous recombinant hCG at the 250 μg label dose produces peak serum concentration of approximately 100 IU/L at 12-24 hours with a terminal half-life of approximately 30-36 hours [1][17][22][23]. Bioavailability after subcutaneous injection is approximately 40-50%. 250 μg of r-hCG is approximately bioequivalent to 6,000-7,000 IU of urinary hCG for the clinical end-point of triggering final follicular maturation, although the original pivotal trial compared it to 10,000 IU urinary hCG and demonstrated non-inferiority [1].

Distribution, Metabolism, and Excretion

hCG distributes in a volume similar to plasma volume (approximately 6-10 L) consistent with its limited tissue penetration beyond gonads and reproductive tract. It is not metabolized by cytochrome P450 enzymes; clearance is primarily renal, with a minor hepatic component. Intact hCG is detectable in urine, forming the basis of urine pregnancy testing [21][23].

Special Populations

Dose adjustment is not required for hepatic or renal impairment within usual clinical ranges; however, clinical data in advanced renal failure are limited. In obesity, IM dosing may be less reliable due to inadvertent subcutaneous deposition, though the label doses accommodate typical patient weights [23].

5. Approved Indications

Ovulation Induction and Luteinization

Following a course of follicle-stimulating hormone (recombinant FSH, human menopausal gonadotropin, or an aromatase inhibitor/clomiphene cycle) to recruit and develop a dominant follicle, hCG is administered as a single "trigger" dose to mimic the mid-cycle LH surge, inducing final oocyte maturation, follicle rupture, and ovulation approximately 36-40 hours later [1][9][17][24]. In assisted reproductive technology, oocyte retrieval is timed for 34-36 hours post-trigger.

Approved dosing:

• Urinary hCG (Pregnyl, Novarel): 5,000-10,000 IU intramuscularly as a single injection
• Recombinant hCG (Ovidrel): 250 μg subcutaneously as a single injection

The Chang 2001 pivotal trial randomized 297 women undergoing IVF-ET to 250 μg r-hCG, 500 μg r-hCG, or 10,000 IU urinary hCG [1]. Pregnancy rates, oocyte yield, and fertilization rates were equivalent across arms. The 500 μg r-hCG dose increased ovarian hyperstimulation syndrome (OHSS) without improving pregnancy rates, establishing 250 μg as the standard and 500 μg as unsafe. Injection-site reactions were significantly more frequent with IM urinary hCG than with SC r-hCG [1].

A 2016 Cochrane review pooled 18 trials (over 2,300 women) of recombinant versus urinary hCG trigger and found no significant difference in live birth, ongoing pregnancy, or oocyte yield [17]. The choice between formulations is therefore largely driven by availability, cost, and patient preference.

For patients at elevated risk of OHSS (particularly those with antral follicle counts above 20 or estradiol concentrations above 4,000 pg/mL), ASRM recommends a GnRH-agonist trigger (for example, triptorelin 0.2 mg or leuprolide 1-2 mg) in place of hCG, because the agonist trigger produces an endogenous LH surge without the prolonged LHCGR stimulation that drives OHSS pathophysiology [9]. Dual triggers combining a GnRH agonist with low-dose hCG are an emerging compromise strategy.

Male Hypogonadotropic Hypogonadism

In men with congenital or acquired hypogonadotropic hypogonadism (HH), including Kallmann syndrome, isolated LH deficiency, pituitary tumors or apoplexy, hemochromatosis, and opioid-induced hypogonadism, hCG substitutes for absent LH to drive Leydig-cell testosterone production [11][12][18]. Typical dosing is 1,000-2,500 IU SC or IM two to three times weekly, titrated to restore mid-normal serum testosterone. hCG monotherapy achieves eugonadal testosterone in approximately 90% of men with secondary hypogonadism [12].

For men with HH who desire fertility, hCG alone may suffice when testicular volume is greater than 4 mL at baseline (indicating some prior FSH exposure, typically post-pubertal onset), but combined hCG + FSH is required in men with pre-pubertal-onset HH or small testicular volume [6][7][8][18]. Combination regimens add recombinant FSH 75-150 IU three times weekly once hCG has restored Leydig-cell function and re-expanded testicular volume over 2-6 months. The Muir 2025 meta-analysis reported spermatogenesis in 86% with combined hCG + FSH versus 40% with hCG alone, with median time to first sperm of 7-12 months [8].

Predictors of successful spermatogenesis induction, established across multiple cohorts and confirmed meta-analytically [6][7][8], include:

• Baseline testicular volume greater than 4 mL (strongest predictor)
• Absence of cryptorchidism history
• Post-pubertal rather than pre-pubertal onset of HH
• No prior exogenous androgen exposure
• Higher baseline serum inhibin B

Cryptorchidism

hCG has historical FDA approval for prepubertal cryptorchidism (undescended testis not due to anatomic obstruction) in boys aged 4 years or older. Typical dosing is 1,500 IU IM twice weekly for 5 weeks (total 15,000 IU divided over 10 doses), with age-adjusted alternatives ranging from 250 IU to 1,500 IU per injection [10]. The mechanism involves testosterone-driven gubernacular maturation and inguinal canal passage.

However, contemporary guidelines, including the American Urological Association 2014 and updated 2025 cryptorchidism guidelines, do NOT recommend hormonal therapy as primary treatment. A meta-analysis of seven randomized controlled trials pooled by Saal and later analyses found a mean descent rate of approximately 20% for true undescended testes, not significantly better than placebo, with retractile testes (which spontaneously descend and do not require treatment) inflating apparent response rates in older literature [10]. Orchidopexy, typically performed at 6-18 months of age, is the definitive treatment. hCG is now rarely used in North American practice, although it retains a role in selected European centers as a pre-operative adjunct to facilitate surgery or in bilateral non-palpable cryptorchidism as a diagnostic test of testicular presence (a testosterone rise confirms functional Leydig tissue).

6. Off-Label Use in Men's Health

Fertility Preservation During TRT

The most common contemporary off-label use of hCG is co-administration with testosterone replacement therapy in men who wish to preserve fertility or testicular volume. Exogenous testosterone suppresses hypothalamic GnRH and pituitary LH/FSH release, collapsing intratesticular testosterone to approximately 1-2% of baseline and arresting spermatogenesis in weeks to months. Approximately 40% of men on standard-dose TRT become azoospermic within 6 months [3][12][15][16].

Coviello et al. (2005) provided the mechanistic foundation by showing that hCG dose-dependently preserved ITT in men on testosterone-induced gonadotropin suppression: 125 IU every other day preserved ITT to 75% of baseline, 250 IU every other day to 93% of baseline, and 500 IU every other day actually raised ITT to 126% of baseline [2]. Hsieh et al. (2013) translated this into clinical practice, showing that hypogonadal men on testosterone plus 500 IU IM hCG every other day had zero cases of azoospermia at 1 year and preserved semen parameters, while achieving normal serum testosterone [3].

Typical off-label protocols include:

• Fertility preservation: testosterone (cypionate, enanthate, or transdermal gel) at standard dose plus hCG 500 IU SC every other day, or 1,000 IU twice weekly
• Testicular volume preservation (no fertility goal): testosterone plus hCG 1,000-1,500 IU weekly

These regimens are endorsed in the Endocrine Society 2018 guideline as an option for men initiating TRT who wish to preserve fertility [11], though the guideline stops short of recommending routine hCG co-administration in all TRT patients.

Recovery After TRT or Anabolic-Androgenic Steroids

Men who have been on exogenous testosterone or anabolic-androgenic steroids and wish to recover endogenous function face a hypothalamic-pituitary-gonadal (HPG) axis that may require months or longer to restart. hCG combined with selective estrogen receptor modulators (SERMs, typically clomiphene citrate or tamoxifen) and sometimes recombinant FSH and/or aromatase inhibitors accelerates recovery [15][16].

Wenker et al. (2015) reported that among 49 men with azoospermia or severe oligozoospermia after prior testosterone or AAS use, treatment with hCG 3,000 IU every other day plus clomiphene 25 mg daily (+/- anastrozole, +/- FSH) restored sperm to the ejaculate or produced significant improvement in 47 of 49 men (96%), with median time to recovery of 4.6 months [15]. Older clinical tradition referred to this as "post-cycle therapy" (PCT) in the bodybuilding literature, but modern andrology has formalized it into an evidence-based recovery protocol [15][16].

hCG Monotherapy in Symptomatic Eugonadal-Range Men

La Vignera et al. (2019) evaluated hCG monotherapy (2,000 IU twice weekly for 3 months) in 41 men with symptoms suggestive of hypogonadism but with total testosterone above 300 ng/dL [13]. Mean testosterone rose from 336 to 527 ng/dL, with significant improvement in ADAM (Androgen Deficiency in the Aging Male) score, IIEF-5 erectile function, and vitality measures. Testicular volume and spermatogenesis were preserved. This approach is philosophically attractive because it raises testosterone via physiological intratesticular steroidogenesis rather than exogenous replacement, though it has not been validated in larger randomized trials.

7. Comparison with Gonadorelin, Buserelin, Triptorelin, and SERMs

For men who wish to preserve or restore fertility while on or after androgen therapy, hCG is one of several available strategies, each operating at a different level of the HPG axis:

• hCG: acts directly on Leydig-cell LHCGR, bypassing the hypothalamus and pituitary. Effective during TRT (because it does not require an intact pituitary). Gold standard for fertility preservation during TRT [2][3][12][16].
• Gonadorelin (native GnRH, 1-10 peptide): acts on pituitary GnRH receptors to stimulate endogenous LH and FSH release. Requires an intact pituitary and usually pulsatile administration via an infusion pump, making it impractical for routine outpatient use. Used in specialist settings for fertility induction in HH.
• Buserelin, triptorelin, leuprolide (GnRH-agonist analogs): cause initial flare followed by pituitary desensitization and suppression of endogenous LH/FSH. Used for suppression indications (prostate cancer, endometriosis, central precocious puberty) and as an ovulation trigger in IVF; NOT used for male fertility preservation because they suppress rather than stimulate gonadotropins.
• Kisspeptin-10 / kisspeptin-54: investigational; stimulates hypothalamic GnRH neurons. Requires intact pituitary. Under investigation as an alternative trigger and for HH.
• Clomiphene / enclomiphene, tamoxifen (SERMs): block hypothalamic estrogen feedback, raising endogenous LH/FSH. Effective in men with intact HPG axis and secondary hypogonadism, but insufficient alone during TRT because exogenous testosterone suppresses the axis centrally.
• Aromatase inhibitors (anastrozole, letrozole): reduce estradiol, lifting estrogen feedback on the hypothalamus. Adjunctive role, not primary therapy.

The practical consequence: during TRT or AAS use, hCG is the only option that preserves testicular function, because it acts downstream of the suppressed hypothalamic-pituitary axis. During HPG recovery after androgen cessation, combinations of hCG + SERM +/- aromatase inhibitor +/- rFSH are used to accelerate restoration [15][16].

8. The Simeons Diet: Not Effective, FDA Enforcement Action

In 1954, British endocrinologist Albert T.W. Simeons published a protocol combining 125 IU daily hCG injections with a highly restrictive 500-kcal/day diet, claiming that hCG mobilized "abnormal fat" without muscle loss and suppressed hunger [4][5]. The protocol has since been revived in numerous commercial iterations, including homeopathic drops, sprays, and pellets marketed directly to consumers.

The scientific evidence is unambiguous that hCG does not contribute to weight loss beyond the caloric restriction of the diet itself:

• Lijesen et al. 1995 performed a criteria-based meta-analysis of 14 controlled trials of hCG for obesity, including the Simeons protocol and variations. There was no consistent effect of hCG on weight loss, fat redistribution, hunger, or sense of well-being compared with placebo injection plus the same diet. The authors concluded that hCG is neither effective as an adjunct therapy for obesity nor supported as bringing about weight loss or fat redistribution [4].
• The FDA has never approved hCG for weight loss. The approved hCG labeling carries a specific warning that hCG has not been demonstrated to be effective adjunctive therapy in the treatment of obesity, that there is no substantial evidence it increases weight loss beyond caloric restriction, or causes a more "attractive" distribution of fat, or that it decreases the hunger and discomfort associated with very-low-calorie diets [23].
• FDA/FTC enforcement (December 2011). In a joint action, the FDA and FTC issued seven warning letters to marketers of "homeopathic" OTC hCG weight-loss products [5]. The agencies stated that hCG is not an approved homeopathic active ingredient, is not listed in the Homeopathic Pharmacopoeia of the United States, and that any hCG-containing product labeled for weight loss is an unapproved new drug. The letters demanded removal from the market within 15 days under threat of seizure, injunction, and criminal prosecution. Subsequent FTC enforcement actions in 2014 and beyond have targeted additional marketers making weight-loss claims [5].
• Safety concerns with the protocol. The 500-kcal/day diet itself, independent of hCG, carries documented risks including symptomatic gallstone formation, electrolyte disturbances (particularly hypokalemia), cardiac arrhythmia, protein-losing malnutrition, and loss of lean body mass. Patients should be counseled that any weight lost on the Simeons protocol is attributable to caloric restriction alone, is frequently regained, and is achieved at the cost of substantial medical risk [4][5].

The persistence of the Simeons protocol in commercial weight-loss clinics, telemedicine compounding pharmacies, and direct-to-consumer marketing, despite more than 70 years of uniformly negative controlled evidence, represents one of the longer-running cases of marketing outpacing science in endocrinology. Prescribers, patients, and researchers should consider hCG prescribed or sold for weight loss to be outside the bounds of evidence-based medicine.

9. Clinical Evidence Summary

10. Dosing in Research

Dosing depends heavily on the indication. Ovulation induction uses a single trigger dose, while male hypogonadism and fertility regimens use chronic maintenance dosing.

11. Safety and Side Effects

Women

The principal safety concern with hCG in women is ovarian hyperstimulation syndrome (OHSS), a potentially serious complication of ovarian stimulation that is precipitated by the prolonged LHCGR stimulation from hCG (and perpetuated by further hCG rise in early pregnancy) [9][17]. OHSS manifests as bilateral ovarian enlargement, abdominal distension, ascites, pleural effusion, hemoconcentration, hypercoagulability, and in severe cases thromboembolism, renal failure, and death. Risk factors include young age, low body weight, polycystic ovary syndrome, antral follicle count greater than 20, peak estradiol greater than 4,000 pg/mL, and development of more than 20 follicles. GnRH-agonist trigger substantially reduces OHSS risk compared with hCG trigger in antagonist-protocol IVF cycles [9].

Other adverse events in women include multiple pregnancy (approximately 20-30% in gonadotropin-stimulated cycles with hCG trigger), injection-site reactions (less with SC r-hCG than IM urinary hCG), ectopic pregnancy (enriched in IVF populations), nausea, headache, and fatigue.

Men

hCG therapy in men is generally well tolerated. Commonly reported adverse effects include:

• Gynecomastia and breast tenderness: hCG-stimulated Leydig-cell testosterone production is accompanied by increased intratesticular and systemic aromatization to estradiol. Elevated estradiol can cause gynecomastia, water retention, and mood lability. Adjunctive aromatase inhibition (anastrozole 0.25-0.5 mg twice weekly) may be used in selected cases, though routine use is not recommended due to risks of excessive estradiol suppression.
• Polycythemia: similar to exogenous testosterone, hCG-driven androgen production can raise hematocrit. Routine hematocrit monitoring is recommended, with phlebotomy or dose reduction if hematocrit exceeds 52-54%.
• Local injection reactions: mild, more common with IM urinary hCG than with SC r-hCG.
• Acne and mood changes: reflect androgen and estradiol changes.
• Testicular pain: uncommon, usually self-limited.

Children

In the pediatric cryptorchidism setting, hCG can precipitate precocious puberty-like effects, including pubic hair development, penile growth, acne, and accelerated bone maturation. These effects are generally reversible after treatment cessation but have contributed to reduced enthusiasm for hormonal therapy in children [10].

General

• Thromboembolism: glycoprotein hormone therapy, particularly in OHSS, has been associated with venous thromboembolism. Prolonged immobilization during severe OHSS should prompt prophylactic anticoagulation.
• Allergic reactions: rare; anaphylaxis has been reported with urinary-derived hCG but not with recombinant forms.
• Ectopic pregnancy risk in women undergoing ART is considered procedural rather than drug-related.

Contraindications

Contraindications include known hypersensitivity to hCG, prior or active sex-hormone-dependent tumors (including prostate carcinoma in men), uncontrolled thyroid or adrenal dysfunction, undiagnosed gynecologic hemorrhage, and premature puberty. Caution is warranted in patients with cardiac, renal, or epilepsy histories.

WADA Status

hCG is prohibited in males at all times under the World Anti-Doping Agency (WADA) Prohibited List, Section S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics). It is not prohibited in females because it occurs physiologically in pregnancy and because its LH-like action is relevant only in males. Competitive male athletes should not use hCG in or out of competition without a Therapeutic Use Exemption.

12. Regulatory Status

hCG has been in continuous clinical use since the 1930s-1940s, initially as crude placental extracts and from the 1950s-1960s as purified urinary-derived preparations (Pregnyl, Novarel, Profasi). Recombinant choriogonadotropin alfa (Ovidrel, EMD Serono; Ovitrelle in the EU) was approved by the FDA in September 2000 and by the EMA in 2001 [1][23].

Approved indications (U.S. FDA):

• Induction of ovulation and pregnancy in anovulatory infertile women pre-treated with follicle-stimulating therapy
• Induction of final follicular maturation and luteinization in infertile women undergoing assisted reproductive technology (ART)
• Selected cases of male hypogonadotropic hypogonadism
• Prepubertal cryptorchidism not due to anatomic obstruction (historical; current guidelines favor orchidopexy)

Explicitly NOT approved (with explicit negative labeling or regulatory action):

• Weight loss, fat redistribution, or appetite suppression (Simeons diet protocol) [4][5][23]

Compounding pharmacies may legally produce hCG for FDA-approved indications in dosage forms not commercially available (for example, multi-dose vials at custom concentrations). Marketing hCG for weight loss is a federal violation regardless of compounding versus manufactured product [5].

13. Related Peptides

See also: Gonadorelin, Kisspeptin-10, Triptorelin, Buserelin

14. References

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