HMG (human menopausal gonadotropin): what it is, the trials and the law

Human menopausal gonadotropin is one of the oldest hormone medicines still in use. After the menopause the ovaries stop responding, so the pituitary pours out FSH and LH, and both hormones are excreted in urine in quantities large enough to collect. A 2004 historical review traces gonadotropin therapy from animal pituitary and pregnant mare serum extracts in the 1930s, through human pituitary and urinary extracts, to the purified urinary and recombinant products used today ^[1]. Urinary HMG (marketed first as Pergonal, and today as Menopur) was the product that made ovulation induction and, later, IVF possible.

The US Menopur label describes it as a preparation of gonadotropins with FSH and LH activity, extracted from the urine of postmenopausal women and subjected to additional purification steps, supplied as a freeze-dried powder for subcutaneous injection ^[2]. The UK summary of product characteristics adds a detail that matters when people compare HMG vs HCG: the LH activity in Menopur comes partly from LH and partly from HCG, and HCG obtained from the urine of pregnant women may be added to reach the required total LH bioactivity ^[3]. Each licensed vial contains 75 IU of FSH activity and 75 IU of LH activity, measured by bioassay against a reference standard ^[2].

HMG is therefore not a single peptide and not something a peptide synthesiser can make. It is a biological extract standardised by activity, which is why an HMG peptide vial from a research vendor is a different proposition from, say, a vial of BPC-157. Its closest relatives on this site are HCG, which supplies LH-like activity alone, the releasing hormone gonadorelin that drives the pituitary to make FSH and LH, and the GnRH agonist triptorelin, which switches that production off. Our guide to what research peptides are covers how the research label works.

FSH acts on granulosa cells in the ovary to recruit and grow follicles, and on Sertoli cells in the testis to support sperm production. LH acts on theca cells in the ovary to supply the androgen precursors for oestrogen, triggers ovulation at mid-cycle, and drives testosterone production by Leydig cells in the testis. Giving both hormones from outside bypasses a hypothalamus or pituitary that is not producing them, or overrides the normal single-follicle selection so that several eggs mature at once for IVF.

In the ovary, HMG is given daily for around a week or more while follicles are tracked by ultrasound and blood oestradiol; when they reach size, a single HCG injection substitutes for the LH surge. In men, the order is reversed: HCG is given first to raise testosterone inside the testis, and FSH-containing HMG is added when sperm do not appear on HCG alone ^[3]. The 2014 meta-analysis of gonadotropin treatment in hypogonadotropic men found higher success when HCG was combined with FSH than with HCG alone ^[8].

The LH content is what distinguishes HMG from recombinant FSH (follitropin alfa or beta), and whether that LH activity helps has been the main scientific argument about the product for 20 years. The MERiT trial found that HMG produced fewer eggs than recombinant FSH (10.0 against 11.8) but a higher share of top-quality embryos (11.3% against 9.0%), with different hormone profiles and endometrial appearance at the end of stimulation ^[4]. Pharmacokinetically, FSH from Menopur has a half-life of about 30 hours after repeated subcutaneous injection; the LH data were too sparse to analyse ^[3].

HMG has been compared with recombinant FSH in two large manufacturer-sponsored randomised trials. MERiT randomised 731 women undergoing IVF after a long GnRH agonist protocol to highly purified HMG or recombinant FSH. The ongoing pregnancy rate per cycle was 27% with HMG and 22% with recombinant FSH (odds ratio 1.25, confidence interval 0.89 to 1.75); superiority could not be concluded, but non-inferiority was established ^[4]. MEGASET randomised 749 women in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Ongoing pregnancy after the fresh cycle was 30% with HMG and 27% with recombinant FSH, and the cumulative live birth rate for one stimulation cycle, counting frozen transfers within a year, was 40% against 38%; again, HMG was at least as effective ^[5].

The 2026 Cochrane review pooled 15 trials with 4,793 participants and found live birth was probably lower with recombinant FSH than with HMG or highly purified HMG (odds ratio 0.83, 95% CI 0.73 to 0.95), that ovarian hyperstimulation syndrome was probably higher with recombinant FSH (OR 1.42), and that clinical pregnancy was probably lower (OR 0.87), all moderate-certainty evidence. The reviewers noted that many studies were industry-sponsored and at unclear risk of bias ^[6]. Read the other way round, the absolute differences are a few percentage points per cycle, and both products are effective.

For ovulation induction in women with polycystic ovary syndrome who have not responded to clomiphene or letrozole, the 2025 Cochrane review found little or no difference in live birth between recombinant FSH and urinary gonadotropins (5 trials, 505 women, low-certainty evidence), and was uncertain whether HMG differed from purified urinary FSH because the trials were tiny (79 women for live birth). Gonadotropins probably produce more live births than continuing clomiphene (relative risk 1.24) ^[7].

In men with hypogonadotropic hypogonadism, HMG supplies the FSH that HCG cannot. The UK SmPC licenses Menopur, in combination with HCG, for stimulation of spermatogenesis in these men, and notes that men with primary testicular failure usually do not respond ^[3]. The 2014 meta-analysis of 44 gonadotropin studies found an overall 75% rate of achieving sperm in the ejaculate, with a mean concentration of about 5.9 million/mL; men whose condition began after puberty did far better than those with prepubertal onset (84% against 68%), previous testosterone treatment did not affect the outcome, and using both HCG and FSH gave a higher success rate than HCG alone ^[8]. In a 29-man series treated in Sydney between 1982 and 1998, the median time to any sperm was 5.5 months and to conception 20.5 months, and the median sperm concentration at conception was only 5 million/mL ^[9].

The men buying HMG for men from research vendors are usually not this group. They are men on testosterone replacement, or recovering from anabolic steroids, whose pituitary output has been suppressed by the testosterone itself rather than by disease. The HCG guide summarises the small case series of HCG-based recovery in that setting; one of them added recombinant FSH at the physician’s discretion ^[8], but we found no controlled trial of HMG specifically in men on testosterone, and no study of HMG for bodybuilding, muscle or testosterone in men with normal pituitary function.

The US Menopur label has a single indication: development of multiple follicles and pregnancy in ovulatory women as part of an assisted reproductive technology cycle, after a full gynaecological and endocrine evaluation, exclusion of pregnancy and primary ovarian failure, and assessment of the male partner ^[2]. The UK licence is broader: anovulation including polycystic ovarian disease in women unresponsive to clomiphene; controlled ovarian hyperstimulation for IVF, GIFT and ICSI; and hypogonadotrophic hypogonadism in men in combination with HCG ^[3].

Both labels state that treatment should be started under a physician experienced in fertility problems, with monitoring facilities available ^{[2] [3]}. The reason is not caution for its own sake: the response of the ovaries to gonadotropins varies enormously between women, and the only way to dose HMG is to measure the response with ultrasound and blood tests every few days. Use outside a fertility clinic, whether from a research vendor or otherwise, removes the monitoring that makes the licensed product usable.

In an IVF cycle, follicles are usually ready for the HCG trigger after roughly 8 to 12 days of daily injections; the US label instructs that the dose is adjusted only after 5 days of treatment, which reflects how long it takes follicles to respond ^[2]. In men, the UK SmPC says treatment should continue for at least three to four months ^[3], and the clinical series show why: months to the first sperm and often more than a year to a pregnancy ^[9]. Nothing about HMG is fast.

These figures describe the labels and trials; they are not recommendations, and none of them can be transferred to a vial of unknown potency. For assisted reproduction, the US label gives a starting dose of 225 IU a day under the skin in the first cycle, with adjustments only after 5 days and by no more than 150 IU at a time, and a maximum of 450 IU a day ^[2]. The UK SmPC, for anovulation, describes starting at 75 to 150 IU daily and stepping up at intervals of at least 7 days until the ovaries respond, with the cycle abandoned if the response is excessive ^[3].

For male infertility, the UK SmPC describes HCG at 1,000 to 2,000 IU two to three times a week first, then menotropin at 75 or 150 IU of FSH with 75 or 150 IU of LH two or three times weekly, continued for at least three to four months ^[3]. That regimen is the closest thing to an HMG dosage for men that exists in a licensed document, and it presupposes semen analysis and hormone monitoring throughout. Because a licensed vial contains 75 IU of each activity, the peptide calculator can convert a 75 IU HMG vial into syringe units, but the arithmetic assumes the label is accurate.

Menopur is a freeze-dried powder reconstituted with sodium chloride solution and injected under the skin; the UK product may also be given into muscle, and the SmPC states the doses are the same for both routes ^{[2] [3]}. Several vials can be dissolved in one millilitre of diluent to reduce injection volume. Being a mixture of large glycoprotein hormones, HMG cannot be taken by mouth or absorbed through the skin, so any oral or nasal HMG product is not delivering the hormones.

The dominant risk is ovarian hyperstimulation syndrome (OHSS). The US label warns that Menopur contains gonadotropic substances capable of causing OHSS with or without pulmonary or vascular complications, along with abnormal ovarian enlargement, thromboembolic events, multiple births and ovarian neoplasms as serious reactions discussed in the labelling ^[2]. The most common adverse reactions in assisted-reproduction trials (2% or more) were abdominal cramps, enlarged abdomen, abdominal pain, headache, injection-site pain, inflammation and reaction, and OHSS ^[2]. The UK SmPC reports OHSS, abdominal pain, headache, abdominal distension and injection-site pain as the most frequent reactions, none at more than 5%, with visual disturbance, nausea, vomiting and fatigue also listed ^[3].

In the Cochrane comparison, OHSS was probably less frequent with HMG than with recombinant FSH (odds ratio 1.42 for recombinant FSH), but it occurs with both ^[6]. Multiple pregnancy is the other well-known consequence of gonadotropin ovulation induction outside IVF, where the number of embryos cannot be controlled. In men, HMG side effects reported on the labels are limited to local reactions and the consequences of raised sex hormones. Because HMG is extracted from pooled human urine, purity and traceability of the source were historically a concern, which is why highly purified and recombinant products were developed ^[1].

A research-labelled HMG vial carries every one of these risks plus the risks of an unregulated product: it may contain more or less activity than stated, may be contaminated, and has not passed through any batch release. The clinical safety record described here belongs to the licensed product used under monitoring.

Menotropins are prescription-only medicines in the UK, US, EU, Canada and Australia. Unlike HCG and HGH, HMG is not a controlled drug under the UK Misuse of Drugs Act, but it is still a medicine, and supplying an unlicensed medicine is an offence under the Human Medicines Regulations; the UK legal status page explains the difference. In the US, Menopur was first approved in 1975 ^[2]; unapproved HMG sold as a research chemical for human use falls under the general prohibition on unapproved new drugs described on the US legal status page. Our legal status overview covers the other markets PepFinder tracks.

In sport, WADA’s Prohibited List bans luteinising hormone in males at all times under section S2.2.1, testosterone-stimulating peptides, and the list applies to substances with similar biological effects ^[10]. HMG contains LH activity, so a male athlete using it would be using a prohibited substance. Female athletes are not covered by that section.

The US label allows the powder to be stored refrigerated or at room temperature (3 °C to 25 °C) until dispensed, protected from light, and says to use it immediately after reconstitution and discard what is left ^[2]. The UK SmPC says do not store above 25 °C, do not freeze, and keep in the original container to protect from light; the multi-dose presentations have their own in-use period after reconstitution ^[3]. The general advice in our guides to storing peptides and bacteriostatic water applies, with the added point that glycoprotein hormones lose activity if shaken or warmed.

PepFinder does not sell HMG. To see what research vendors charge, compare HMG prices, with separate UK and US listings. The test that matters for HMG is potency: the licensed product is assayed in international units of FSH and LH activity, and a certificate of analysis that reports only a mass-spectrometry identity check is not telling you how many units are in the vial. Our guides to reading a peptide COA and third-party peptide testing explain the difference, and the third-party tested and published COAs lists show which vendors publish results. A vendor offering HMG as an oral product or a spray is selling something other than menotropins; see how to spot a fake peptide supplier.