HMG

Origin and structure

After the menopause the ovaries stop responding and the pituitary releases large amounts of the two gonadotrophins, FSH and LH, which pass into the urine. In 1950 they were first extracted from the urine of postmenopausal women, and the Italian company Serono registered the first preparations that same year. Later products were standardised to equal amounts of both activities: Pergonal 75, for example, held 75 IU of FSH and 75 IU of LH. Early in the 1960s Bruno Lunenfeld's group reported the first pregnancies after stimulation with hMG followed by an hCG injection.

Purification later removed much of the LH, so hCG was added back to restore the 1:1 ratio. The highly purified menotrophin in Menopur therefore contains FSH, a little LH and hCG; according to its product information the LH activity comes mainly from hCG, and hCG from the urine of pregnant women may be added to reach the required amount. Meriofert likewise contains hCG from the urine of pregnant women.

FSH, LH and hCG are glycoproteins: large hormones built from two protein chains with sugar side chains, far bigger than the short peptides in most of this wiki. hMG is a mixture, so it has no single sequence or molar mass; its CAS number is 61489-71-2. Doses are given in international units (IU) that are defined by animal bioassays (ovarian weight gain in female rats for FSH, seminal vesicle weight gain in male rats for LH) against a WHO reference standard, not by weight.

How it works

The FSH activity acts on the ovaries: it raises the number of follicles that grow and drives their growth. FSH also lets the granulosa cells inside each follicle turn androgens into oestradiol; those androgens are made by the neighbouring theca cells under the influence of LH. The LH activity supports this hormone production and the final development of follicles ready to ovulate. For ovulation induction the aim is a single mature follicle; for IVF and ICSI it is several, so that more eggs can be collected. In both cases a separate hCG injection triggers the final maturation once the follicles are large enough on ultrasound.

In men, the FSH activity matures the Sertoli cells in the testes and with them the production of sperm, but only when testosterone inside the testes is high. That is why the label first gives hCG to bring testosterone to normal and adds menotrophin afterwards.

After repeated injections the FSH in Menopur has an elimination half-life of about 30 hours under the skin and 27 hours in the muscle, according to the European product information; the US label gives 11 to 13 hours after repeated dosing in its own study. FSH leaves the body mainly through the kidneys.

Is hMG approved?

Yes. hMG is an authorised, prescription-only fertility medicine in the Netherlands and the US. In Europe it is not authorised centrally by the EMA but country by country, so the Dutch register is the place to check.

Research-grade HMG, sold in vials labelled 75 IU for laboratory use, is not one of these medicines. It has no marketing authorisation, no regulator has assessed it, and it may not be used in people. The approvals below describe the branded products, not the research material.

• Netherlands: Menopur 75 IU (Ferring) has been registered with the CBG since 13 July 1999 (RVG 24536) and Meriofert (IBSA) since January 2015, through a European procedure with Denmark as reference country. Both are prescription-only. Menopur may be injected under the skin or into a muscle, and its indications are infertility from anovulation, including polycystic ovary syndrome, after clomiphene has failed; controlled ovarian stimulation for IVF, GIFT and ICSI; and, in men, selected cases of impaired sperm production due to insufficient stimulation of the testes.
• Dutch practice: fertility treatment takes place in specialist hospital care. For anovulation in PCOS the Farmacotherapeutisch Kompas names letrozole (off-label) as first choice and clomiphene as second, with gonadotrophins after that.
• US: Menopur (menotropins for injection) was approved on 29 October 2004. Its label covers only the development of multiple follicles and pregnancy in ovulatory women as part of assisted reproduction, given under the skin. Earlier US products, Pergonal, Humegon and Repronex, are listed by the FDA as discontinued, leaving Menopur as the only menotropins product on the market.

What the research shows

Highly purified hMG has been compared head to head with recombinant FSH in several large randomised trials; the two MEGASET trials were sponsored by its maker, Ferring. Each was designed to show that hMG is not worse, and each did; none proved higher pregnancy rates. The main results:

• EISG trial (Fertil Steril 2002): 781 women enrolled at 22 centres in six countries, two of the centres in the Netherlands, all on a long GnRH agonist protocol. Ten weeks after egg collection, 25% (85 of 344) on hMG and 22% (71 of 317) on recombinant FSH had an ongoing pregnancy; OHSS, miscarriage and side effects were similar. This is the trial behind the US approval.
• MERIT (Hum Reprod 2006): 731 women having IVF after a long agonist protocol. Ongoing pregnancy 27% on hMG versus 22% on recombinant FSH (odds ratio 1.25, 95% CI 0.89 to 1.75), so not inferior but not proven superior. Fewer eggs were collected with hMG (10.0 versus 11.8), but a larger share became top-quality embryos (11.3% versus 9.0%).
• MEGASET (Fertil Steril 2012): 749 women at 25 centres in seven countries, GnRH antagonist protocol with compulsory single-blastocyst transfer. Ongoing pregnancy after the fresh transfer 29% versus 27%; counting frozen transfers within a year, 40% versus 38% had a live birth.
• MEGASET-HR (Fertil Steril 2020): 620 women in the US predicted to respond strongly (AMH of at least 5 ng/ml). Ongoing pregnancy 35.5% on hMG versus 30.7%; OHSS 9.7% versus 21.4%, and cumulative early pregnancy loss 14.5% versus 25.5%. Cumulative live births were similar, 50.6% versus 51.5%.
• Ovulation induction (Hum Reprod 2006): 184 women who did not ovulate on clomiphene (WHO group II) were randomised to hMG or recombinant FSH in a low-dose step-up regimen. Ovulation rates were 85.7% and 85.5%; OHSS or cancellation for an excessive response occurred in 2.2% versus 9.8%, a difference that just missed statistical significance.
• Meta-analysis and guideline: a Cochrane review of 42 trials with 9,606 couples compared recombinant FSH with all urinary gonadotrophins (hMG and purified urinary FSH) and found no difference in live births (28 trials, 7,339 couples; odds ratio 0.97, 95% CI 0.87 to 1.08) or OHSS. The 2025 update of the ESHRE guideline on ovarian stimulation still recommends recombinant FSH and hMG equally (strong recommendation, moderate-quality evidence).

hMG, FSH and hCG compared

The fertility hormones are easy to mix up. hMG combines FSH and LH activity. FSH alone comes as purified urinary FSH (urofollitropin) or as recombinant follitropin alfa, beta or delta, made in cell lines; recombinant LH (lutropin alfa) and a fixed combination of recombinant FSH and LH also exist. hCG is a single hormone with LH-like activity: in women it is the injection that triggers final egg maturation, and in men it raises testosterone in the testes.

Urinary and recombinant products give similar live-birth rates in the trials above, and the European guideline treats them as equal choices. hMG is also distinct from the gonadotrophins once extracted from the pituitaries of the dead, which were withdrawn after they were linked to Creutzfeldt-Jakob disease.

Finally, HMG has nothing to do with HMG-CoA reductase, the liver enzyme that statins block, or with HMB, a leucine metabolite sold as a sports supplement. The shared letters are a coincidence.

Side effects and warnings

According to the European product information, the side effects reported most often in Menopur trials are ovarian hyperstimulation syndrome (OHSS), a bloated abdomen, abdominal pain, headache and pain at the injection site, none of them in more than 5% of women. In the two IVF trials behind the US label (434 women), abdominal pain affected 6.7%, headache 6.2%, OHSS 6.2% and injection-site pain or reaction 3.9%.

Severe OHSS is the main danger: fluid shifts into the abdomen and sometimes the chest, with rapid weight gain, shortness of breath, little urine and a risk of blood clots. An excessive ovarian response rarely leads to OHSS unless hCG is given to trigger ovulation, which is why hCG is withheld when the ovaries respond too strongly. OHSS usually peaks seven to ten days after treatment and can be more severe and last longer if pregnancy occurs. The labels also warn about ovarian torsion, blood clots in women with risk factors, multiple pregnancy (30 of 85 pregnancies, 35%, in the IVF trial behind the US label), miscarriage, and ectopic pregnancy, which the European product information puts at 2 to 5% of pregnancies after IVF against 1 to 1.5% in the general population. Antibodies can form after repeated cycles and make treatment ineffective. Benign and malignant ovarian tumours have been reported in women who had many fertility treatments, without a proven causal link.

The labels exclude women with unexplained vaginal bleeding, tumours of the uterus, ovaries, breast, pituitary or hypothalamus, or enlarged ovaries or cysts not caused by PCOS, and men with prostate cancer or a testicular tumour. Treatment belongs with a fertility specialist who can monitor the ovaries by ultrasound and oestradiol levels.

Frequently asked questions

Is HMG legal in the Netherlands?

Yes, as a medicine on prescription. Menopur (Ferring) and Meriofert (IBSA) are registered with the CBG as prescription-only medicines, and fertility specialists prescribe them for IVF, ICSI or ovulation induction. Research-grade HMG is not a registered medicine, so it may not be sold or supplied for use in people.

Is HMG banned in sport?

For men, yes, at all times, in and out of competition. The Dopingautoriteit's 2026 list of prohibited substances names menopausal gonadotrophin in class S2, together with hCG and LH, with the note that these are prohibited only for men; LH and hCG drive testosterone production in the testes. For women they are not on the list.

What is the difference between HMG and hCG?

HMG contains both FSH and LH activity and is used for several days to make follicles grow. hCG is a single hormone with LH-like activity, given once to trigger the final maturation of the eggs, or in men to raise testosterone. In today's highly purified HMG, hCG supplies most of the LH activity, so the two often appear in the same treatment.

Is Menopur the same as HMG?

Yes. Menopur is Ferring's brand of highly purified menotrophin, the international name for hMG. Meriofert (IBSA) is the other brand registered in the Netherlands. Older brands such as Pergonal and Humegon are no longer marketed in the US.

Is research-grade HMG the same as Menopur?

No. Menopur is a licensed medicine whose FSH and LH content is set in international units by animal bioassays against a WHO reference standard, and it is made and tested under pharmaceutical rules. Research-grade HMG is sold for laboratory use; its identity and purity are what a certificate of analysis says, nothing more, and a purity test alone does not measure biological activity in IU. It may not be used in people.

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.