HCG

Origin and structure

hCG is made by the placenta from the start of pregnancy, and it is the hormone that pregnancy tests detect. Its effect was first shown in 1927, when Aschheim and Zondek found that pregnant women produce a substance that, injected into immature female mice, made their ovaries mature and ovulate.

It is a glycoprotein of two subunits held together by weak, non-covalent forces rather than a fixed bond. The alpha subunit is the same one found in LH, FSH and TSH; the beta subunit is what makes hCG distinct. The whole molecule weighs about 36 kDa, and an unusually large share of that, roughly 25 to 30%, is sugar side chains.

As a medicine it comes in two forms. Urinary hCG is purified from the urine of pregnant women and dosed in international units (IU), a measure of biological activity: Pregnyl and Gonasi are examples. Choriogonadotropin alfa is recombinant hCG made in Chinese hamster ovary cells, sold as Ovitrelle in Europe and Ovidrel in the US; it has the same amino-acid sequence as urinary hCG and is dosed by weight, with 250 micrograms corresponding to about 6,500 IU.

How it works

hCG binds the LH/CG receptor, which it shares with luteinising hormone, and its action is virtually identical to that of LH. In pregnancy it keeps the corpus luteum producing progesterone after LH from the pituitary has fallen away.

In women undergoing fertility treatment, a single dose does the job of the LH peak that normally arrives halfway through the cycle: it completes the maturation of the eggs, triggers ovulation and turns the emptied follicle into a corpus luteum that makes progesterone and oestradiol. In men it stimulates the Leydig cells of the testes to make testosterone. Testosterone inside the testis is normally far higher than in the blood, around 80 times in one study, and sperm production depends on it. Testosterone given as a medicine shuts down the body's own LH and with it testicular testosterone; hCG replaces the missing LH signal. It has little FSH activity of its own, which is why men with pituitary hypogonadism often also receive FSH to start sperm production.

After an injection under the skin the half-life is about 30 hours for recombinant hCG, of which about 40% reaches the blood, and about 37 hours for urinary hCG, so levels stay raised for several days after a single dose. The US label states that hCG has no known effect on fat mobilisation, appetite or body-fat distribution.

Is hCG approved?

Yes, as a prescription medicine in the EU and the US, but the approved uses differ.

In the Netherlands two products are registered, both prescription-only. Ovitrelle was authorised by the EMA in February 2001 and is held by Merck Europe in Amsterdam. Gonasi 5000 IE, a urinary hCG from the Italian company IBSA, was registered by the CBG in June 2021 and is also on the register as parallel imports. Both are labelled for women only: to trigger ovulation, or the final maturation of the eggs before IVF, once the follicles have been stimulated. Pregnyl, Organon's urinary hCG, is not in the Dutch register, and no product registered in the Netherlands carries an indication for men, so treating men with hCG falls outside the Dutch registered indications.

Research-grade hCG, sold in vials labelled in IU for laboratory use, is not one of these medicines. It has no marketing authorisation, is not made under a medicines licence and may not be used in people. The approvals below describe the licensed products, not the research material.

• EU: Ovitrelle (choriogonadotropin alfa) authorised on 2 February 2001 for women undergoing superovulation before IVF and for women who ovulate rarely or not at all, after stimulation of follicle growth; 250 micrograms in a pre-filled syringe or pen. Urinary hCG is authorised country by country; in the Netherlands that is Gonasi.
• US: Pregnyl, approved in October 1976, is labelled for undescended testes in boys without an anatomical obstruction, selected cases of hypogonadotrophic hypogonadism in men, and ovulation induction; Novarel (Ferring) and a generic chorionic gonadotropin from Fresenius Kabi also have current labels, and recombinant Ovidrel has been approved since September 2000. On 23 March 2020 these products became licensed biologics, and since then compounded hCG no longer qualifies for the pharmacy-compounding exemptions.
• Weight loss: not approved anywhere. The US label states that hCG has not been shown to be effective in treating obesity.
• Sport: the WADA Prohibited List names chorionic gonadotrophin in class S2.2.1, testosterone-stimulating peptides prohibited in males at all times; the 2027 list, published in September 2026, announced no change to this class. The Dutch anti-doping rules apply the same list.

What the research shows

Because hCG has been a medicine for decades, most modern trials compare it with alternatives rather than ask whether it works at all. In fertility the evidence is large and randomised; in men it is smaller, and part of it is uncontrolled. The main findings:

• Recombinant versus urinary hCG as IVF trigger (Cochrane review, Youssef et al. 2016): 18 randomised trials with 2,952 participants. Recombinant and urinary hCG showed no clear difference in ongoing-pregnancy or live-birth rates (odds ratio 1.15, 95% CI 0.89 to 1.49; 7 trials, 1,136 women), with no difference in ovarian hyperstimulation syndrome. In the comparative trials in its product information, 250 micrograms of Ovitrelle was as effective as 5,000 and 10,000 IU of urinary hCG.
• Men with pituitary hypogonadism (Rastrelli et al. 2014): a meta-analysis of 44 studies of gonadotrophin treatment found sperm in the semen of 75% of men (95% CI 69 to 81%). Success was higher when hCG was combined with FSH, and lower in studies limited to men whose disorder began before puberty (68% against 84% in mixed groups).
• Testosterone in hypogonadal men (Habous et al. 2018): 282 men who wanted to keep their fertility were randomised to clomiphene, hCG 5,000 IU twice a week, or both, for three months. All three treatments raised testosterone, on average to more than double the baseline, with no significant difference between them.
• Alongside testosterone therapy (Coviello et al. 2005): in 29 healthy men given weekly testosterone enanthate, testosterone inside the testis fell by 94% on placebo; 250 IU of hCG every other day kept it within 7% of baseline, and 500 IU raised it 26% above baseline. The study ran for three weeks and measured testicular testosterone, not sperm production.
• Fertility during testosterone therapy (Hsieh et al. 2013): a retrospective chart review of 26 men on testosterone plus 500 IU of hCG every other day found no one became azoospermic during a mean follow-up of 6.2 months, and 9 contributed to a pregnancy. There was no control group.
• Weight loss (Lijesen et al. 1995): a meta-analysis from the Vrije Universiteit Amsterdam of 24 trials of the hCG diet found no scientific evidence that hCG causes weight loss, redistributes fat or reduces hunger.

Side effects and warnings

In fertility treatment the main risk is ovarian hyperstimulation syndrome (OHSS), in which the ovaries swell and fluid leaks into the abdomen and sometimes the chest. hCG plays a key role in triggering it, and it is more severe and lasts longer if pregnancy follows. With Ovitrelle, OHSS occurred in about 4% of women and severe OHSS in fewer than 0.5%. Multiple pregnancy, ovarian torsion and, very rarely, blood clots are the other serious risks. Headache, abdominal pain or bloating, nausea and injection-site reactions are common.

In men the US label lists water and sodium retention at high doses and occasional breast enlargement (gynaecomastia); in boys treated for undescended testes it can bring on early puberty. Irritability, restlessness, depression, fatigue and allergic reactions, rarely anaphylaxis, are reported in both sexes. The labels exclude people with tumours of the prostate or breast in men, of the ovary, uterus or breast in women, or of the pituitary or hypothalamus.

Because hCG is what pregnancy tests measure, a dose can give a false-positive test for up to ten days.

hCG and weight loss

The hCG diet, also called the Simeons method after the doctor who promoted it, combines hCG injections with a strict low-calorie diet and is promoted as a way to lose fat without hunger. Controlled trials did not support it. The Amsterdam meta-analysis scored 24 trials on quality and found most of them poor; of the 12 better studies, only one judged hCG useful, and the authors concluded there is no scientific basis for its use in obesity.

The US label puts it bluntly: there is no substantial evidence that hCG adds to the weight loss from calorie restriction, that it gives a more attractive distribution of fat, or that it reduces the hunger of a calorie-restricted diet. Whatever weight is lost on the diet is explained by eating very little.

Frequently asked questions

Is hCG legal in the Netherlands?

hCG is a registered prescription medicine in the Netherlands: Ovitrelle and Gonasi are supplied on prescription and labelled for female fertility treatment. Research-grade hCG is not a registered medicine, so it may not be sold, advertised or supplied for use in people; buying and selling it as research material is a different status, which our guide on research-use-only products in the Netherlands explains. For male athletes under anti-doping rules it is prohibited regardless of how it was obtained.

Is hCG banned in sport?

For men, yes, at all times, in and out of competition. The WADA Prohibited List names chorionic gonadotrophin in class S2.2.1, testosterone-stimulating peptides in males, because it raises the body's own testosterone production. It is not prohibited for women. The 2027 list, published in September 2026, announced no change to this rule, and the Dutch anti-doping rules apply the same list.

Does hCG help with weight loss?

No. A 1995 meta-analysis of 24 trials from the Vrije Universiteit Amsterdam found no scientific evidence that hCG causes weight loss, redistributes fat or reduces hunger, and the US label states it has not been shown to work in obesity. The weight lost on the hCG diet comes from the very low calorie intake that goes with it.

What is the difference between Ovitrelle and Pregnyl?

Ovitrelle is recombinant hCG made in cell culture and given as 250 micrograms, about 6,500 IU, under the skin. Pregnyl and Gonasi are urinary hCG purified from the urine of pregnant women and dosed in IU; Pregnyl's US label is for injection into the muscle, Gonasi can also go under the skin. The amino-acid sequence is the same, and a Cochrane review found no clear difference in pregnancy or live-birth rates when either was used to trigger egg maturation in IVF. In the Netherlands the registered urinary product is Gonasi; Pregnyl is not in the Dutch register.

Can hCG preserve fertility during testosterone therapy?

The evidence is small. In a randomised study of 29 healthy men, low doses of hCG kept testosterone inside the testis close to normal while they received testosterone injections, but the study lasted three weeks and did not measure sperm production. A retrospective review of 26 men on testosterone plus hCG found no one became azoospermic over about six months, without a control group. No registered product in the Netherlands is labelled for this use.

Does hCG cause a positive pregnancy test?

Yes. Pregnancy tests detect hCG, so an injection can give a false-positive result in blood or urine for up to ten days, as the Ovitrelle product information warns.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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