HCG (Human Chorionic Gonadotropin) (Pregnyl) — what it does, evidence, and safety

What it is

HCG (human chorionic gonadotropin) is best known for stimulating the testicles to make testosterone (it acts like luteinizing hormone, LH) and for triggering ovulation in fertility treatment. It's a large glycoprotein hormone, not a small peptide, and it's dosed in international units (IU) rather than milligrams. It's FDA-approved (as Pregnyl, Novarel, and others) for male hypogonadism and ovulation induction; using it alongside testosterone therapy to keep the testicles working is a common off-label use.

What the research found

HCG is studied in men to support testosterone production and fertility, and it's FDA-approved as a hormone for related uses. A 2005 study found low-dose HCG maintained testosterone inside the testicles in men whose own hormone signaling was suppressed by testosterone; a 2013 study found adding HCG during testosterone therapy preserved sperm production; and a 2015 case series reported high rates of sperm-production recovery using HCG-based combination therapy after testosterone use. These uses are off-label but supported by published clinical evidence.

Status and regulatory position

FDA-approved under multiple biologics license applications (Pregnyl BLA 017692 [Organon, originally approved 1974], Novarel BLA 017016 [Ferring, originally approved 1974], Ovidrel/Ovitrelle BLA 021149 [recombinant choriogonadotropin alfa, EMD Serono, approved 2000]) — Drugs@FDA classifies all three as BLAs, not NDAs — for prepubertal cryptorchidism, hypogonadotropic hypogonadism in males, and induction of ovulation in selected women undergoing infertility treatment. Not DEA-scheduled (unlike testosterone — HCG is not a controlled substance under federal law, though it is prescription-only). WADA-banned in regulated sport — explicitly listed as *"chorionic gonadotrophin (CG)"* under Section S2.2.1 (Testosterone-stimulating peptides in males) of the 2026 Prohibited List. Note: WADA's S2.2.1 listing is sex-specific — HCG is prohibited in males. Currently sold as a prescription drug (in regulated channels) and as a research peptide (in some jurisdictions where research-supply chains exist).

Safety

HCG is a prescription drug (not a controlled substance) and is banned in male athletes under WADA rules; because it raises testosterone, it can also raise estrogen. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

Disclosures

⚠️ For research and educational purposes only. HCG is FDA-approved as a prescription drug for specific indications (cryptorchidism, hypogonadotropic hypogonadism in males, ovulation induction in selected women). Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ Precision matters at low draws. HCG is dosed in IU (international units), not mg or mcg — a distinct unit system from the rest of the Vialwise library. Typical TRT-adjunct doses at typical reconstitution concentrations produce small draws in the range on a U-100 syringe. At those draw sizes, even a one-unit error is a meaningful percentage of the dose. Always verify draws against the in-app calculator and double-check the unit count on the syringe before injecting. The Vialwise calculator handles IU-dosed compounds — confirm the units field shows "IU" before entering the dose.

⚠️ HCG is not a small peptide. This entry exists in the Vialwise library because researchers running peptide protocols frequently use HCG alongside testosterone or GH-secretagogue stacks. The compound is a 244-amino-acid heterodimeric glycoprotein hormone consisting of an α subunit (shared with LH, FSH, and TSH) and a β subunit (HCG-specific) — substantially larger and structurally more complex than the small peptides covered elsewhere in this library. Mechanistically, HCG functions as an LH (luteinizing hormone) analog at the LHCG receptor on Leydig cells (in males) and theca/granulosa cells (in females), stimulating endogenous testosterone production in males and inducing ovulation in females. HCG is not a peptide in the small-peptide / research-peptide sense. Compound class is meaningfully different from the rest of the library; researchers should be explicit with themselves about which compound class they are using.

⚠️ IU dosing — different from mg/mcg. HCG is dosed in International Units (IU), a potency-based unit that does not directly correspond to a mass measurement. Vials are sold by IU content ( and are the most common), and reconstitution converts a vial's IU content into an IU/mL concentration. The Vialwise calculator math for HCG is: dose target (IU) ÷ concentration (IU/mL) → draw volume (mL → insulin-syringe units). This is structurally similar to the mcg-dosed peptides (concentration-based draw conversion) but uses IU rather than mg/mcg. Standard reconstitution practice: 1 mL bacteriostatic water per of HCG (so + 5 mL BAC =; + 10 mL BAC =). Many research-community protocols dilute further (e.g. + 10 mL BAC =) to produce more readable draws at typical dose targets.

⚠️ Three distinct use cases — different doses, different evidence bases, different regulatory contexts. HCG is used in three pharmacologically and regulatorily distinct contexts that are easy to conflate: 1. TRT adjunct (testicular preservation during testosterone replacement) — low-dose ( SC, 2–3× weekly) added to ongoing TRT to maintain testicular size, intratesticular testosterone, and spermatogenesis. Off-label but widespread clinical practice supported by the Coviello 2005[¹] and Hsieh 2013[²] evidence. 2. Fertility recovery / spermatogenesis rescue (post-TRT or post-AAS) — higher doses ( SC, 2–3× weekly), often combined with a SERM (clomiphene, tamoxifen) or recombinant FSH, to recover spermatogenesis after testosterone-induced HPG-axis suppression. Evidence base: Wenker 2015[³] retrospective series. 3. Hypogonadotropic hypogonadism treatment (FDA-approved indication) — IM 2–3× weekly per Pregnyl/Novarel labels for adult-male hypogonadism secondary to pituitary/hypothalamic dysfunction.[⁴][⁵] Plus the FDA-approved indications for cryptorchidism (boys, separate dosing) and ovulation induction (women, single trigger dose). Researchers should be explicit with themselves about which use case applies and which evidence base supports the specific dose/cycle pattern they are following.

Quick reference

Compound class	244-amino-acid heterodimeric glycoprotein hormone (α + β subunits). Not a small peptide. Functions as an LH analog at the LHCG receptor.
Common vial sizes	and lyophilized powder vials (Pregnyl, Novarel, generic compounded). Single-dose pre-filled formulations also exist (Ovidrel ≈ recombinant).
Frequency	Variable by use case — 2–3× weekly is the most common cadence for TRT adjunct and hypogonadism; every-other-day patterns also reported.
Half-life	Subcutaneous: ~32–33 hours (urinary-derived hCG); ~45 hours terminal (recombinant choriogonadotropin alfa). Significantly longer than the small peptides.
Route	Subcutaneous (most common in modern clinical and research-community practice); intramuscular (FDA-label-approved route per Pregnyl/Novarel labeling).[⁴][⁵]
Onset of action	Endogenous testosterone elevation typically detectable within 24–48 hours post-injection. Subjective effects on testicular size and intratesticular testosterone observable over days to weeks of consistent dosing.

In depth

HCG (human chorionic gonadotropin) is a 244-amino-acid heterodimeric glycoprotein hormone, not a small peptide. The molecule consists of two non-covalently linked subunits: an α subunit (92 amino acids — shared with the pituitary glycoprotein hormones LH, FSH, and TSH) and a β subunit (145 amino acids — HCG-specific, with substantial structural homology to the LH β subunit). HCG is produced naturally by the syncytiotrophoblast cells of the placenta during pregnancy; the molecule's namesake biological role is supporting the corpus luteum during early pregnancy. Pharmacologically, HCG functions as an LH analog at the LHCG receptor — in males, this stimulates Leydig-cell testosterone production; in females, it triggers ovulation when administered at the appropriate point in the menstrual cycle.

Pharmacological identity vs LH. HCG and LH bind the same receptor (LHCG-R) and produce highly similar downstream effects (testosterone production via Leydig cells, ovulation/luteinization via theca/granulosa cells). HCG has a substantially longer half-life than LH (~32–33 hours subcutaneous vs ~30 minutes for endogenous LH), which makes it a more practical pharmaceutical agent. Most therapeutic uses of HCG could conceptually be substituted with LH if a long-acting LH preparation existed; HCG's longer half-life is the reason it is the dominant agent in clinical practice.

Regulatory status (US). HCG is FDA-approved under multiple NDAs spanning multiple branded products and routes: - Pregnyl (Organon, BLA 017692, originally approved 1974) — IM, urinary-derived hCG, for cryptorchidism, hypogonadotropic hypogonadism in males, and ovulation induction[⁴] - Novarel (Ferring, BLA 017016, originally approved 1974) — IM, urinary-derived hCG, same indications as Pregnyl[⁵] - Ovidrel / Ovitrelle (EMD Serono, BLA 021149, approved 2000) — SC, recombinant choriogonadotropin alfa ( pre-filled syringe ≈), specifically for ovulation induction - Profasi (Serono, historical) — discontinued in the US - Generic compounded HCG is widely available through compounding pharmacies for off-label uses (TRT adjunct, fertility recovery)

Availability note. Branded urinary-derived products (Pregnyl, Novarel), recombinant Ovidrel, and generic hCG remain manufactured (not discontinued), but urinary-derived products have seen intermittent shortages / inconsistent availability since roughly 2020 (Novarel in particular). FDA enforcement has curtailed compounded hCG supply, shifting demand onto the FDA-approved products — so availability can vary by product and period.

Not FDA-approved for weight loss. HCG is not FDA-approved for weight loss or obesity. The FDA and the FTC have acted against over-the-counter drug products labeled "homeopathic" HCG and marketed for weight loss — issuing warning letters and classifying such products as unapproved and illegally marketed — and the FDA states the available evidence does not support the safety or efficacy of HCG for weight loss (FDA, ["Questions and Answers on HCG Products for Weight Loss"](https://www.fda.gov/drugs/medication-health-fraud/questions-and-answers-hcg-products-weight-loss)). This is a regulatory fact about those products, not a claim about any individual's use.

HCG is not a DEA controlled substance. Unlike testosterone (Schedule III under the Anabolic Steroid Control Act), HCG is not scheduled under federal law. It is prescription-only but does not carry the controlled-substance regulatory framework. The off-label use of HCG for TRT-adjunct testicular preservation, fertility recovery, and PCT is widely practiced under prescriber supervision in the US.

Regulatory status (sport — WADA). HCG is explicitly listed under Section S2.2.1 (Testosterone-stimulating peptides in males) of the 2026 WADA Prohibited List as *"chorionic gonadotrophin (CG)"*. The S2.2.1 listing is sex-specific — HCG is prohibited at all times in males. The other compounds listed under S2.2.1 (luteinizing hormone, GnRH analogs like buserelin/deslorelin/goserelin/histrelin/leuprorelin/nafarelin/triptorelin, kisspeptin and analogues) share the same male-specific prohibition framing. This is a meaningfully different prohibition profile from testosterone (S1.1, prohibited at all times in all athletes regardless of sex) or the unapproved peptides covered elsewhere in this library (S2.2.4 GHRH/GHS, S2.3 growth factors).[⁶]

The three use-case framings. HCG appears in three distinct contexts in modern research-community and clinical practice:

1. TRT adjunct (testicular preservation during testosterone replacement). Exogenous testosterone suppresses the hypothalamic-pituitary-testicular (HPT) axis through negative feedback, reducing endogenous LH and FSH. Reduced LH means reduced Leydig-cell stimulation, which reduces intratesticular testosterone and spermatogenesis. Adding low-dose HCG ( SC, 2–3× weekly) directly stimulates Leydig cells via the LHCG receptor, bypassing the suppressed pituitary LH pathway and maintaining intratesticular testosterone production. The Coviello 2005 paper demonstrated that every other day maintains intratesticular testosterone within ~26% above baseline in men on exogenous testosterone with full HPT-axis suppression.[¹] Hsieh 2013 demonstrated that concomitant HCG during TRT preserves spermatogenesis in men actively trying to conceive.[²] A large 2026 retrospective cohort (n=6,999) further reported that hCG combined with testosterone therapy raised total and free testosterone to physiologic levels, comparable to clomiphene-based regimens.[⁷]

2. Fertility recovery / spermatogenesis rescue (post-TRT or post-AAS). Researchers and clinicians treating testosterone-induced infertility (azoospermia or severe oligospermia after TRT or AAS use) typically administer HCG at higher doses (often SC every other day) combined with a SERM (clomiphene, tamoxifen) and/or recombinant FSH. Wenker 2015 reported 95.9% spermatogenesis recovery with this combination protocol in a retrospective case series.[³]

3. PCT (post-cycle therapy) in research-community / AAS contexts. Similar to fertility recovery but typically with shorter duration and not necessarily aimed at conception. Common protocols use 2–3× weekly for 2–4 weeks, often as a bridge before SERM-based PCT (Nolvadex/Clomid). The published evidence for PCT-context HCG specifically is thinner than the fertility-recovery and TRT-adjunct evidence; most PCT protocols are research-community-derived. A 2026 narrative review addresses this off-label post-cycle-therapy / anabolic-steroid-induced-hypogonadism context directly.[⁹]

Reported side effects

Commonly reported

Injection site reactions — local pain, redness, mild swelling
Estradiol elevation — HCG drives endogenous testosterone production, which aromatizes to estradiol; symptomatic hyperestrogenism (gynecomastia, water retention, mood changes) is dose-dependent
Mild gynecomastia — at higher doses or with prolonged use, particularly in men with elevated baseline aromatase activity
Acne, oily skin — testosterone-mediated; typically mild
Mood changes — variable; some men report improved mood/energy, others report irritability or anxiety
Headache, fatigue — uncommon; typically transient
Ovarian hyperstimulation syndrome (OHSS) — relevant only to ovulation-induction context in women; not applicable to TRT-adjunct or fertility-recovery use in men. Severe OHSS is a serious adverse event in IVF/IUI contexts and the relevant Pregnyl/Novarel/Ovidrel labels carry specific warnings.[⁴][⁵]

Serious

Severe acute chest pain, shortness of breath — possible thromboembolic event (VTE risk slightly elevated with hCG in some populations, particularly women undergoing ovulation induction)
Severe abdominal pain or distension (especially in women — possible OHSS)
Severe psychiatric changes (mania, severe aggression, psychosis) — uncommon but reported with very high doses
Sudden visual changes — relevant in pituitary-deficient populations
Allergic / hypersensitivity reactions

Contraindications and warnings

Known or suspected androgen-dependent neoplasm (e.g., prostate cancer in men) — HCG drives endogenous testosterone production and would be contraindicated

Precocious puberty in pediatric patients — HCG can induce premature pubertal development

Pregnancy — HCG is appropriate for ovulation induction but is contraindicated in established pregnancy outside specific obstetric indications

Hypersensitivity to HCG or any product component

Pregnancy and lactation: HCG is naturally produced during pregnancy; therapeutic use in pregnancy is limited to specific obstetric contexts under specialist supervision.

Concurrent use of testosterone: the most common stacking pattern (TRT adjunct); not contraindicated but requires monitoring of estradiol, hematocrit, and PSA per the Bhasin 2018 testosterone guideline framework. See [testosterone.md](./testosterone.md).

Concurrent use of fertility medications: HCG is intentionally combined with menotropins, FSH, and SERMs in fertility contexts; specialist supervision is the standard of care for these regimens.

Regulatory note (US): HCG is not a DEA-scheduled controlled substance but IS a prescription drug — possession outside an authorized prescriber relationship is a regulatory issue but not a controlled-substance criminal offense. This is a meaningful distinction from testosterone (Schedule III).

Regulatory note (sport): HCG is explicitly listed in WADA 2026 Prohibited List Section S2.2.1 as *"chorionic gonadotrophin (CG)"*, prohibited at all times in males.[⁶] Researchers competing in any WADA-tested sport will test positive on standard HCG assays.

Regulatory note (weight loss): HCG is not FDA-approved for weight loss. The FDA and FTC have taken action against OTC "homeopathic" HCG weight-loss products as unapproved and illegally marketed; the FDA states the available evidence does not support HCG's safety or efficacy for weight loss (see the FDA Q&A linked in the About section).

Key terms

Testosterone: The principal male sex hormone, important for sexual development, muscle and bone, and other functions.
Subcutaneous: An injection into the fatty layer just under the skin, rather than into a muscle or vein.
International unit (IU): A potency-based unit of measurement used for some drugs (such as HCG) instead of milligrams.
Testosterone replacement therapy (TRT): Medically supervised use of testosterone to treat men with diagnosed low testosterone.

Sources

Related entries

Testosterone — discussed together in this entry's stacks section
CJC-1295 / Ipamorelin Blend — discussed together in this entry's stacks section
Gonadorelin — same mechanism class
Kisspeptin — same mechanism class
Clomiphene / Enclomiphene — shared research area
Melanotan II — shared research area