HCG

HCG (human chorionic gonadotropin) is a natural glycoprotein hormone, not a synthetic peptide, that is also an FDA-approved injectable drug. Outside of pregnancy testing and obstetric care, it is prescribed for specific male and female fertility-related conditions, including hypogonadotropic hypogonadism and undescended testicles in boys, and it is also used off-label, alongside testosterone replacement therapy (TRT), to help maintain testicular size and function in men. This entry focuses on that injectable, TRT-adjacent and fertility-related use, not on HCG as a pregnancy-test analyte.

Research snapshot

Category	Current information
Peptide category	Glycoprotein hormone (not a simple synthetic peptide)
Primary research interest	Male and female fertility conditions; off-label testicular preservation during testosterone replacement therapy
Highest available evidence	FDA-approved prescribing information for its labeled indications; the off-label TRT use rests on one randomized dose study in healthy men and a small retrospective series
Human research available	Yes, decades of clinical use; the TRT-adjacent fertility-preservation use is widely practiced but off-label and not settled by a large modern randomized trial
Development status	Long-established, decades-old marketed biologic hormone
Regulatory status	FDA-approved (US approval dating to 1974 for Pregnyl; Health Canada 2015) for prepubertal cryptorchidism, male hypogonadotropic hypogonadism, and ovulation induction; TRT-adjacent use is off-label

Technical identity

Technical property	Information
Primary name	Human chorionic gonadotropin (HCG)
Alternative names	hCG; brand names Novarel, Pregnyl (urinary-derived), Ovidrel (recombinant, choriogonadotropin alfa); “HCG trigger shot”
Peptide sequence	Not a simple peptide sequence. HCG is a heterodimeric glycoprotein hormone: an alpha subunit of 92 amino acids (shared with LH, FSH and TSH) noncovalently paired with a hormone-specific beta subunit of 145 amino acids, both carrying attached carbohydrate (glycosylation) chains
Amino-acid length	Alpha subunit 92 residues + beta subunit 145 residues (237 total across both subunits, plus glycosylation)
Molecular formula	Not established as a single fixed formula; HCG is a heterogeneously glycosylated glycoprotein, not a single small molecule
Molecular weight	Sources commonly cite an approximate mass in the mid-30 kilodalton range for the intact hormone, but this varies with glycoform and is not independently re-derived here from a single authoritative reference
CAS Registry Number	9002-61-3
PubChem CID	Not established
Chemical modifications	Natively glycosylated (carbohydrate chains attached to both subunits)
Peptide class	Glycoprotein hormone (gonadotropin family, shares an alpha subunit with LH, FSH and TSH)
Primary biological target	Luteinizing hormone/choriogonadotropin receptor (LHCGR)
Developer or originator	Naturally produced by the placenta; pharmaceutical product purified from urine (Novarel, Pregnyl) or produced as recombinant choriogonadotropin alfa (Ovidrel)
Development status	Approved, marketed drug (DrugBank DB09126)

What it is

Human chorionic gonadotropin is a glycoprotein hormone made of two subunits, an alpha subunit shared with luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone, and a beta subunit that gives it its distinct identity and is the basis of pregnancy tests. It is naturally produced by the placenta during pregnancy, but the pharmaceutical product used clinically is either purified from the urine of pregnant women (urinary HCG, brand names including Novarel and Pregnyl) or manufactured as recombinant choriogonadotropin alfa (brand name Ovidrel). Its CAS Registry Number is 9002-61-3, and its DrugBank identifier is DB09126.

Because its beta subunit closely resembles LH, HCG binds and activates the same receptor as LH, the luteinizing hormone/choriogonadotropin receptor (LHCGR). In men, LH is the pituitary signal that tells the testes’ Leydig cells to produce testosterone and support sperm production; HCG mimics that signal. This is why HCG is used clinically, and off-label, whenever a person wants to stimulate the testes to keep producing testosterone and sperm through the LH receptor pathway, whether because the pituitary itself is not sending that signal (hypogonadotropic hypogonadism) or because an external testosterone product has suppressed the body’s own LH output (as happens during TRT).

HCG is a long-approved drug. The FDA lists its original approval for Pregnyl going back to 1974, and it remains on the market today under brand names including Novarel and Pregnyl (urinary-derived) and Ovidrel (recombinant). Because it is a decades-old, off-patent biologic hormone rather than a novel research peptide, most of what circulates about “HCG protocols” online concerns dosing patterns for its off-label TRT-adjacent use, which sits outside its original approved indications, rather than questions about whether the hormone itself is real or how it is made.

How does it work?

Plain-English explanation

The brain normally tells the testes to keep making testosterone by sending a hormone called LH. When a man takes external testosterone (as in TRT), the brain senses plenty of testosterone is already present and stops sending that LH signal, which is part of why the testes can shrink and sperm production can drop during TRT. HCG looks enough like LH to the testes that it can substitute for that missing signal, keeping the testes actively working even while the brain’s own signal is switched off.

Technical explanation

HCG binds the LHCGR receptor on testicular Leydig cells with LH-like agonist activity, stimulating steroidogenesis (intratesticular testosterone production) and, through the resulting local androgen environment, supporting Sertoli cell function relevant to spermatogenesis. In exogenous-testosterone-suppressed men, negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis reduces endogenous LH and FSH pulsatility; HCG bypasses that suppressed step by acting directly at the LHCGR, independent of pituitary LH output, which is the pharmacological basis for its co-administration with testosterone therapy in men who want to preserve testicular volume, endogenous intratesticular testosterone production, or fertility potential.

Potential benefits and research applications

Approved use: cryptorchidism (undescended testicles) in boys

What is being investigated: this is an established, FDA-approved indication, not an open research question. How the effect might occur: HCG’s LH-like stimulation of testicular Leydig cells is used to try to induce testicular descent in prepubertal boys whose cryptorchidism is not due to anatomical obstruction. Evidence: this is a long-standing FDA-approved indication (Pregnyl label). Strength: has been shown sufficient for regulatory approval decades ago. Limitation: it does not work in every case, particularly where the cause is anatomical rather than hormonal, and modern pediatric urology often favors surgical correction (orchiopexy) as primary therapy.

Approved use: hypogonadotropic hypogonadism in men

What is being investigated: this is an established, FDA-approved indication. How the effect might occur: HCG substitutes for absent or insufficient pituitary LH signaling in men whose hypogonadism originates above the testes (secondary/hypogonadotropic hypogonadism), stimulating the testes directly. Evidence: FDA-approved indication (Pregnyl/Novarel labeling). Strength: has been shown sufficient for regulatory approval and is standard endocrinology practice for this specific diagnosis. Limitation: it is not the correct treatment for primary (testicular) hypogonadism, where the testes themselves cannot respond regardless of LH-like stimulation.

Approved use: ovulation induction in anovulatory infertile women

What is being investigated: this is an established, FDA-approved indication. How the effect might occur: HCG’s LH-like surge triggers final oocyte maturation and ovulation after follicular development has been induced with other gonadotropins. Evidence: FDA-approved indication, used as the standard “trigger shot” in assisted reproduction and ovulation induction. Strength: well established in reproductive endocrinology. Limitation: this is the general obstetric/fertility-clinic use of HCG in women and is not the focus of this entry, which centers on injectable male fertility and TRT-adjacent use.

Off-label use: preserving testicular size and fertility during TRT (widely practiced, limited controlled human trial data)

What is being investigated: whether adding HCG to testosterone replacement therapy in men preserves testicular volume, intratesticular testosterone, and spermatogenic potential that would otherwise decline on testosterone alone. How the effect might occur: HCG maintains LHCGR stimulation of the testes independent of the pituitary suppression caused by exogenous testosterone. Evidence: this is a widely practiced clinical strategy described in urology and endocrinology literature and used by many TRT-prescribing clinicians, and it follows directly and plausibly from HCG’s established LH-like mechanism. Strength: has been reported in the clinical and practitioner literature as effective for maintaining testicular size and semen parameters in men on testosterone therapy; this is not, however, an FDA-approved indication for HCG, and this site did not identify a large, modern, placebo-controlled randomized trial establishing one specific optimal HCG dose or regimen for this exact purpose. Limitation: dosing for this use is off-label and practitioner-driven rather than FDA-reviewed, and reported regimens vary considerably between clinics.

What dosage information circulates?

Figures in this section summarize amounts and schedules reported in published research, the approved drug label, or circulating online. Their inclusion documents what is reported and does not establish that a regimen is verified, safe, effective, or appropriate for any individual reader.

Reported use or research objective	Route reported	Amount reported	Frequency reported	Reported duration	Evidence or source category
Prepubertal cryptorchidism (boys ages 4-9)	Intramuscular injection	4,000 USP units (or alternative FDA-labeled schedules of 500-5,000 units)	Three times weekly (or per alternative label schedule)	3 weeks (or per alternative label schedule up to 6 weeks)	FDA-approved prescribing information (Pregnyl label)
Hypogonadotropic hypogonadism in men	Intramuscular injection	500-1,000 USP units, later 4,000 USP units	Three times weekly, tapering to twice weekly	3 weeks to 6-9 months depending on regimen	FDA-approved prescribing information (Pregnyl label)
Ovulation induction in anovulatory infertile women	Intramuscular injection	5,000-10,000 USP units	Single dose, one day after last gonadotropin dose	Single administration	FDA-approved prescribing information (Pregnyl label)
Off-label testicular/fertility preservation during TRT	Subcutaneous injection	Roughly 250-500 IU	Two to three times weekly	Continued alongside testosterone therapy indefinitely, or cycled around fertility attempts	Practitioner / community reported

Amounts studied in human research / approved by FDA

The Pregnyl FDA label specifies the following approved regimens. For prepubertal cryptorchidism (children ages 4 to 9): 4,000 USP units three times weekly for 3 weeks, OR 5,000 USP units every other day for 4 injections, OR 500 to 1,000 USP units given as 15 injections over 6 weeks, OR 500 USP units three times weekly for 4 to 6 weeks (a repeat series at 1,000 units may be tried if the first course is unsuccessful). For hypogonadotropic hypogonadism in men: 500 to 1,000 USP units three times weekly for 3 weeks, then the same amount twice weekly for 3 weeks, OR 4,000 USP units three times weekly for 6 to 9 months, then reduced to 2,000 USP units three times weekly for an additional 3 months. For ovulation induction in women: 5,000 to 10,000 USP units given one day following the last dose of another gonadotropin.

Off-label use alongside testosterone therapy has far less trial data than the labeled uses. The published human numbers this page found are below. The first is an uncontrolled case series and the second is a short randomized study in healthy volunteers, so neither tests a long-term TRT regimen against a control.

Research objective	Amount studied	Frequency	Duration	Route	Study population	Source
Keeping semen parameters stable during testosterone replacement	500 IU	Every other day	Hormones followed a mean of 6.2 months; semen parameters followed more than 1 year	Intramuscular	26 hypogonadal men, mean age 35.9, retrospective review	Hsieh 2013
Raising intratesticular testosterone during induced gonadotropin suppression	15, 60 or 125 IU, plus a 0 IU control arm	Every other day	10 days	Subcutaneous	37 healthy men aged 18 to 50 given the GnRH antagonist acyline, randomized	Roth 2012

In plain English: in the series, none of the 26 men became azoospermic (no sperm in the ejaculate) while taking testosterone plus 500 IU every other day, and 9 of the 26 contributed to a pregnancy (Hsieh 2013). There was no comparison group. In the randomized study, hCG at 15, 60 and 125 IU raised testosterone inside the testes in a dose-dependent way over 10 days (Roth 2012), but that is a hormone measurement, not sperm counts or fertility. Two reviews describe low-dose hCG as able to sustain intratesticular testosterone and sperm production during TRT while noting the evidence is limited (Lee and Ramasamy 2018; Naelitz 2025); this page did not extract dose figures from them.

Where the circulating figure sits: 250 to 500 IU subcutaneously two to three times a week works out to about 500 to 1,500 IU a week, while 500 IU every other day is about 1,750 IU a week. The per-injection amount is well above the 15 to 125 IU used subcutaneously in the randomized study. No trial this site found compared subcutaneous with intramuscular dosing, so the route difference between the circulating figure and the published series is unresolved. This arithmetic is an illustration, not a suggested amount.

Amounts studied in animal research

Not consistently reported. This entry focuses on HCG’s long-established human clinical and regulatory dosing rather than on animal pharmacology, since HCG has been a marketed human drug for decades and its dosing is governed by an FDA label rather than by translated animal data.

Practitioner and community-reported protocols (off-label TRT-adjacent use)

Widely repeated online, but original sourcing varies by clinic: for men on testosterone replacement therapy who want to preserve testicular size and fertility potential, TRT-prescribing clinicians and community/forum sources commonly describe injecting roughly 250 to 500 international units (IU) of HCG two to three times per week, subcutaneously, continued alongside testosterone therapy indefinitely or cycled around fertility attempts. This is a practitioner- and community-reported convention built on HCG’s approved mechanism and its off-label extension to this use, not a figure drawn from the FDA label’s approved indications, and this site did not identify a single large, modern, placebo-controlled randomized trial that established this specific range as an optimal or standardized dose for TRT-adjacent testicular preservation. Reported amounts and frequencies vary meaningfully between clinics and online communities discussing this use.

Side effects, risks, and limitations

The FDA label lists adverse effects that can include headache, irritability, restlessness, depression, fatigue, edema (fluid retention), gynecomastia (breast tissue development) in men, and injection site pain or bruising. Ovarian hyperstimulation syndrome is a recognized risk specific to its use in ovulation induction in women. Because HCG raises testosterone through LH-receptor stimulation, off-label TRT-adjacent use shares some of the general risks associated with elevated androgen levels, including potential effects on hematocrit, mood, and estrogen conversion (since testosterone can aromatize to estradiol), and clinicians typically monitor bloodwork during use. As with any injectable product obtained outside a licensed pharmacy chain, unregulated or vendor-sourced HCG carries added risks around purity, correct concentration, and sterility that do not apply to the FDA-approved pharmaceutical product dispensed by prescription.

Regulatory and developmental status

HCG is an FDA-approved prescription product, not an investigational compound, and since March 2020 it is regulated as a biological product. Per the FDA label reviewed for this entry (Pregnyl), it is approved for prepubertal cryptorchidism not due to anatomical obstruction, hypogonadotropic hypogonadism in men, and induction of ovulation in anovulatory infertile women who have been appropriately pretreated with other gonadotropins; DrugBank lists Health Canada approval in 2015 and the original US approval in 1974. Its use alongside testosterone replacement therapy specifically to preserve testicular size or fertility is off-label: it is not one of the indications named on the approved label, even though it uses the same approved drug and the same underlying mechanism.

Since 23 March 2020, FDA has treated chorionic gonadotropin as a biological product rather than a drug; before that date it was approved under drug applications. In its notice to compounders, FDA lists human chorionic gonadotropin among the transitioning products and states that they are not eligible for the 503A and 503B compounding exemptions, while noting it may exercise limited discretion for certain mixing, diluting or repackaging under its January 2018 guidance.

In practice, licensed products such as Pregnyl and Novarel are the FDA-regulated route, and compounding hCG from bulk powder is not a recognized pathway under that notice. This page has not verified what any particular clinic or pharmacy dispenses.

Frequently asked questions

What is HCG?

A naturally occurring glycoprotein hormone, also manufactured as an FDA-approved injectable drug, that mimics luteinizing hormone (LH) and stimulates the testes (in men) or triggers ovulation (in women).

How does HCG work in men?

It binds the same receptor as LH on testicular Leydig cells, stimulating testosterone production and supporting the testicular environment needed for sperm production, even when the pituitary’s own LH signal is suppressed.

What dosage has been studied or approved?

The FDA-approved label specifies weekly injection schedules ranging from 500 to 4,000 USP units per injection depending on the indication (cryptorchidism, hypogonadotropic hypogonadism, or ovulation induction), given two to three times weekly for several weeks to several months.

What dosage commonly circulates for TRT-adjacent use?

Commonly reported online: roughly 250 to 500 IU, two to three times weekly, alongside testosterone therapy. This is a practitioner- and community-reported off-label convention, not an FDA-approved dose for this specific purpose.

Can HCG be compounded?

Not from bulk powder, according to FDA. Its 2020 notice to compounders lists human chorionic gonadotropin among the products that became biological products on 23 March 2020 and are no longer eligible for the 503A and 503B compounding exemptions. FDA noted limited discretion for mixing, diluting or repackaging under a January 2018 guidance. This page has not verified what individual pharmacies do.

Is using HCG with TRT an FDA-approved use?

No. HCG is FDA-approved for cryptorchidism, hypogonadotropic hypogonadism, and ovulation induction. Using it specifically to preserve testicular size or fertility during testosterone replacement therapy is an off-label, though widely practiced, use of an approved drug.

Does HCG help fertility in men on TRT?

It is reported in the clinical and practitioner literature to help maintain testicular volume and spermatogenic potential during testosterone therapy, consistent with its LH-like mechanism, but this site did not identify a large modern randomized trial establishing one specific optimal regimen for this exact purpose.

What side effects have been reported?

Headache, irritability, fatigue, fluid retention, gynecomastia in men, and injection site reactions are listed on the FDA label. Ovarian hyperstimulation syndrome is a specific risk in its use for ovulation induction in women.

Is HCG a peptide?

It is a glycoprotein hormone made of two peptide subunits with attached sugar chains (glycosylation), not a simple synthetic peptide like most other compounds on this site.

What remains unknown?

A single, standardized, trial-established optimal dose and schedule for the specific off-label goal of preserving fertility and testicular size during TRT; reported clinical practice varies, and this use sits outside the FDA-reviewed approved indications.

Bottom line

HCG is a well-established, FDA-approved hormone drug with genuine, decades-old approved indications in cryptorchidism, male hypogonadotropic hypogonadism, and female ovulation induction, each with a specific approved dosing regimen on its label. Its use alongside testosterone replacement therapy to preserve testicular size and fertility is a widely practiced, mechanistically sound extension of that same LH-mimicking action, but it is off-label, and the specific regimens reported online for that purpose (commonly around 250 to 500 IU two to three times weekly) come from practitioner convention and community reporting rather than from a dedicated large randomized trial establishing one correct dose for that exact use.