HCG (human chorionic gonadotropin): what it does, the evidence and the law

Human chorionic gonadotropin is the hormone that home pregnancy tests detect. It is made by the placenta from the first days after implantation, and its main early job is to keep the corpus luteum in the ovary producing progesterone so the pregnancy is maintained. A 2010 review from the USA hCG Reference Service describes it as a molecule of two subunits held together by non-covalent bonds, with a molecular weight of about 36,000, an unusually large share of which (25 to 30% in regular HCG) is carbohydrate rather than protein ^[1]. The same review lists a long tail of other roles in pregnancy, from promoting blood vessel growth in the uterus to suppressing contractions, and describes several distinct HCG-related molecules, including a hyperglycosylated form made by invading placental cells and a free beta-subunit produced by some cancers ^[1].

HCG matters to people outside pregnancy because its receptor is the same one that luteinising hormone (LH) uses. In a woman, the mid-cycle LH surge triggers ovulation, and the US Pregnyl label explains that HCG can substitute for LH in that role ^[2]. In a man, LH tells the Leydig cells of the testes to make testosterone, so an injection of HCG does the same thing. That is why HCG injection is used in fertility clinics, why it is prescribed to some men with pituitary-based hypogonadism, and why it is bought by men on testosterone who want to keep their testes working.

Two kinds of licensed product exist. Urinary HCG (Pregnyl, Novarel, Choragon, Gonasi) is purified from the urine of pregnant women. Recombinant HCG, choriogonadotropin alfa (Ovitrelle in Europe, Ovidrel in the US), is made in cell culture; a 2002 pharmacokinetic programme in healthy volunteers found that the two behave similarly in the body, with the recombinant version offering a secured source and higher purity ^[10]. Vials sold by research peptide vendors are neither: they carry no marketing authorisation, and their content is whatever the vendor’s supplier put in them. Our guide to what research peptides are explains why that label matters. HCG is usually discussed alongside HMG (which supplies FSH as well as LH activity), the releasing hormone gonadorelin and the GnRH agonist triptorelin.

HCG binds the LH/HCG receptor on ovarian theca and granulosa cells and on testicular Leydig cells. In the ovary, a single large dose given at the end of follicle stimulation mimics the natural LH surge and completes the maturation of the egg, so that it can be released or collected about 36 hours later. In the testes, HCG drives testosterone production inside the testis. The concentration of testosterone within the testis is far higher than in blood: in a 2005 study of 29 healthy men, baseline serum testosterone was 1.2% of the intratesticular concentration (14.1 against 1,174 nmol/L) ^[6]. That gradient is what spermatogenesis depends on, and it collapses when the pituitary stops making LH.

That collapse is exactly what happens on testosterone treatment or anabolic steroids. In the same study, 200 mg of testosterone enanthate a week suppressed LH and FSH to 5% and 3% of baseline and cut intratesticular testosterone by 94%. Adding HCG every other day restored it in a dose-dependent way: 125 IU left it 25% below baseline, 250 IU left it 7% below, and 500 IU took it 26% above baseline ^[6]. This is the mechanistic basis for HCG as an add-on to testosterone therapy.

HCG has a much longer life in the body than LH, which is one reason it is used clinically instead of LH itself. Recombinant HCG given under the skin or into muscle had an absolute bioavailability of 40 to 50%, and levels rose about 1.7-fold during repeated subcutaneous dosing ^[10]. The Pregnyl label is explicit about what HCG does not do: it states that HCG has no known effect on fat mobilisation, appetite or sense of hunger, or body fat distribution ^[2].

Searches for HCG for men and for the HCG peptide usually come down to three claimed HCG benefits: fertility treatment in women, testosterone and sperm production in men, and weight loss. The first two rest on licensed indications and clinical studies. The third has been tested and rejected.

In women, HCG is the standard trigger for final egg maturation in IVF and ICSI. A 2016 Cochrane review compared recombinant HCG and recombinant LH against urinary HCG for this purpose and found the drugs comparable, with the recombinant products offering less batch-to-batch variation and no urinary contaminants ^[11]. It is also licensed to induce ovulation in anovulatory women after a course of gonadotropins such as HMG ^[2].

In men, the best-studied use is alongside testosterone. In a retrospective series of 26 hypogonadal men on testosterone (injections or gel) who also took 500 IU of HCG into muscle every other day, serum testosterone rose from 207 to 1,056 ng/dL, no man became azoospermic, semen parameters did not change over more than a year of follow-up, and nine of the 26 contributed to a pregnancy ^[7]. A second series looked at 49 men who were azoospermic or had very low sperm counts while taking testosterone: on 3,000 IU of HCG every other day plus clomiphene, tamoxifen, anastrozole or FSH, 47 (95.9%) recovered sperm production, after an average of 4.6 months ^[8]. Both are uncontrolled case series from single centres, and neither tells you what would have happened without HCG. The American Urological Association’s 2018 guideline nevertheless lists HCG among the options clinicians may use in men with testosterone deficiency who want to maintain fertility ^[15].

In men whose hypogonadism is caused by the pituitary or hypothalamus (hypogonadotropic hypogonadism), gonadotropin treatment can start sperm production in men who have none. A 2014 meta-analysis of 44 studies found an overall success rate of 75% for appearance of sperm, with a mean sperm concentration of about 5.9 million/mL; results were better when the disorder began after puberty and when HCG was combined with FSH ^[12]. In a 29-man Sydney series, the median time to the first sperm was 5.5 months and the median time to conception was 20.5 months, which is a reminder that this is slow treatment ^[16].

HCG for weight loss is a different story. The 1950s Simeons protocol combined HCG injections with a 500-calorie-a-day diet. A 1995 meta-analysis of 24 trials found most were of poor quality; of the 12 better studies, only one reported HCG as a useful adjunct, and the authors concluded there is no scientific evidence that HCG causes weight loss or fat redistribution, reduces hunger or improves wellbeing ^[4]. The US labels carry the same conclusion in capital letters: HCG has not been demonstrated to be effective adjunctive therapy in the treatment of obesity, and there is no substantial evidence that it increases weight loss beyond that from calorie restriction ^{[2] [3]}. The FDA states that there are no approved HCG products for weight loss and that HCG diet drops and sprays sold over the counter are illegally marketed ^[5].

The US Pregnyl label lists three indications: prepubertal cryptorchidism (undescended testes) not caused by anatomical obstruction, usually in boys aged 4 to 9; selected cases of hypogonadotropic hypogonadism in males; and induction of ovulation and pregnancy in anovulatory women who have been treated with gonadotropins ^[2]. Novarel’s label is the same ^[3]. The FDA summarises this as approval for select cases of female infertility and hormone treatment in men, available only as an injection on prescription ^[5]. In the UK, the Menopur summary of product characteristics describes menotropins being given together with HCG (it names Choragon) to stimulate spermatogenesis in men with hypogonadotrophic hypogonadism, which reflects the same pairing ^[18].

Everything else is off-label or unlicensed. HCG alongside testosterone replacement to preserve fertility is off-label but described in the urology literature ^{[7] [8]} and acknowledged in guidelines ^[15]. HCG as “post-cycle therapy” after anabolic steroids, sometimes with a selective oestrogen receptor modulator, is discussed in a 2014 review of anabolic-steroid-induced hypogonadism; the authors intended a meta-analysis but found no studies of sufficient quality to include, so their recommendations are expert opinion ^[9]. HCG as a weight-loss drug is not a legitimate use at all ^{[4] [5]}.

The people buying HCG from research peptide stores are overwhelmingly in the second and third groups: men on testosterone or coming off steroids, and people following an HCG diet. None of the licensed evidence applies to those products, because the evidence was generated with pharmaceutical HCG whose potency is measured in USP or international units against a reference standard. A research vial labelled 5,000 IU has not been measured against anything unless a third-party test says so.

In IVF, egg collection is scheduled about 36 hours after the trigger injection, so the ovulatory effect is measured in hours. In men, testosterone rises within days: in the volunteer studies, a single dose of recombinant HCG produced comparable increases in serum testosterone, inhibin and oestradiol by any injection route ^[10]. Sperm production is far slower. Men recovering from testosterone-related azoospermia took an average of 4.6 months to show sperm again ^[8], and men with hypogonadotropic hypogonadism took a median of 5.5 months to produce any sperm and over two years to reach 20 million/mL ^[16].

Reported here for information; none of these figures is a recommendation. The Pregnyl label gives several regimens. For cryptorchidism: 4,000 USP units three times weekly for three weeks; 5,000 USP units every second day for four injections; 15 injections of 500 to 1,000 USP units over six weeks; or 500 USP units three times weekly for four to six weeks. For hypogonadotropic hypogonadism in men: 500 to 1,000 USP units three times a week for three weeks, then the same dose twice a week for three weeks; or 4,000 USP units three times weekly for six to nine months, then 2,000 USP units three times weekly for a further three months. For ovulation induction: a single 5,000 to 10,000 USP unit injection one day after the last dose of gonadotropins ^[2].

In the studies of men on testosterone, the doses were 125, 250 or 500 IU every other day for three weeks in the intratesticular testosterone study ^[6], 500 IU every other day in the 26-man fertility-preservation series ^[7], and 3,000 IU every other day in the 49-man recovery series ^[8]. Whether HCG is dosed daily, every other day or twice weekly, the total weekly amount in these studies ranged from under 1,000 IU to over 10,000 IU, and the appropriate figure depended entirely on the goal and on monitoring of testosterone, oestradiol and semen. HCG dosage for men on TRT is therefore not a single number, and the published series were run by fertility specialists with blood tests.

Pregnyl is supplied as a 10,000 USP unit vial reconstituted with 1 to 10 mL of solvent, which means the concentration, and therefore the number of syringe units per dose, varies with how much diluent is used ^[2]. The peptide calculator shows the arithmetic for a 5,000 or 10,000 IU HCG vial, but it cannot tell you whether a research vial actually contains what its label says.

Licensed urinary HCG is a freeze-dried powder for intramuscular injection after reconstitution ^{[2] [3]}. Recombinant HCG (Ovitrelle/Ovidrel) is given under the skin, and the pharmacokinetic studies found subcutaneous and intramuscular routes bioequivalent for recombinant HCG ^[10]; the off-label series in men used both intramuscular ^[7] and subcutaneous ^[8] injection. HCG drops, pellets and sprays sold for the HCG diet are not HCG in any meaningful sense: they are labelled homeopathic, and the FDA has said that all drug products claiming to contain homeopathic HCG are illegally marketed ^[5]. Because HCG is a large glycoprotein, it is not absorbed by mouth.

In women, the serious risk on the labels is ovarian hyperstimulation syndrome (OHSS), which the Pregnyl label describes as a medical event distinct from simple ovarian enlargement that may progress rapidly to become serious, with a dramatic increase in vascular permeability. The label also warns of thromboembolic events both with and separate from OHSS, including stroke, pulmonary embolism and arterial occlusion leading to loss of a limb, multiple births, and anaphylaxis, which has been reported with urinary-derived HCG products ^[2]. Novarel adds that HCG may cause fetal harm and is contraindicated in precocious puberty and androgen-dependent cancers such as prostate cancer ^[3].

In men, the effects follow from raising testosterone and oestrogen. The fertility-preservation series recorded a rise in oestradiol alongside testosterone ^[7], and gynaecomastia, water retention, acne and mood change are the expected consequences of that hormonal shift. In boys treated for cryptorchidism, the label notes that HCG stimulates androgen production and can bring on early sexual development, and that testicular descent is usually temporary ^[2]. The 49-man recovery series reported that no man stopped HCG because of adverse events ^[8], but it had no placebo group and was not designed to measure harms.

The weight-loss context adds a separate hazard. The FDA points out that the very-low-calorie diets sold with HCG carry their own risks, including gallstones, electrolyte imbalance and heart rhythm disturbances, and should only be followed under medical supervision ^[5]. Unlicensed HCG vials add the risks of every unregulated injectable: unknown potency, possible bacterial contamination and no batch release. A urinary-derived hormone also raises the question of source purity, which is one reason the recombinant product was developed ^[10].

HCG is a prescription-only medicine in the UK, US, EU, Canada and Australia. In the UK it is also a controlled drug: Part III of Schedule 2 to the Misuse of Drugs Act 1971 lists chorionic gonadotrophin as a Class C drug alongside anabolic steroids and somatropin ^[14]. Possession for personal use is not an offence for Class C anabolic substances in that part of the schedule, but supply is, and importing for supply is; our UK legal status page sets out the detail. In the US, HCG is approved only as an injection on prescription; the FDA and the Federal Trade Commission have issued joint warning letters to companies selling over-the-counter HCG diet products ^[5], and the US legal status page covers the federal position on unapproved drugs. Rules for other markets differ again.

For athletes, HCG is prohibited at all times in males under section S2.2.1 of the WADA Prohibited List, which covers testosterone-stimulating peptides including chorionic gonadotrophin, LH, GnRH and its agonist analogues, and kisspeptin ^[13]. It is not prohibited in females, because it is a normal pregnancy hormone in women. An HCG vial sold as a research chemical is not a licensed medicine anywhere, is not manufactured under a marketing authorisation, and is not covered by the safety data on this page.

The Pregnyl label says to store the unopened vial at controlled room temperature (15 °C to 25 °C), and to refrigerate the reconstituted solution at 2 °C to 8 °C, discard it after 60 days, and never freeze or shake it ^[2]. Novarel is reconstituted with bacteriostatic water and used within 30 days refrigerated ^[3]. The US labels warn that benzyl alcohol, the preservative in bacteriostatic water, has been linked to a fatal gasping syndrome in premature infants ^[3]. See our guides to bacteriostatic water and how to store peptides; a glycoprotein of this size is more easily damaged by heat and agitation than a short peptide.

PepFinder does not sell HCG. If you are comparing research suppliers, compare HCG prices, including UK listings and US listings. Potency is the issue with HCG rather than sequence purity: the licensed product is standardised in international units by bioassay, and a certificate of analysis for a research vial should say how the stated IU figure was measured. Our guide to how to read a peptide COA explains what a genuine report shows, and the third-party tested and published COAs lists show which vendors publish batch results. If a vendor sells HCG as drops or a spray, that alone is a warning sign; see how to spot a fake peptide supplier and third-party peptide testing.