HMG

Dosing from the Literature

Published for fertility: Menopur’s label doses for women in IVF (225 IU a day to start, 450 IU a day at most, 20 days at most) and, for men, 75–150 IU one to three times a week with hCG, on the discontinued Pergonal’s label and in mostly retrospective or uncontrolled studies. Not published: a men’s dose on Menopur’s label, or a trial of HMG taken alongside TRT.

Menopur’s label gives doses for one use: women in IVF. The label of Pergonal, a menotropins product now discontinued, also gave a dose for men. The other men’s rows come from studies, a case report and a review; several of the studies adjusted doses against testosterone levels (Lin et al., 2019; Shah et al., 2021). The rows record the doses as published; they are not recommendations.

What It Is

HMG, human menopausal gonadotropin, is sold in the US as Menopur (menotropins for injection). The label calls it “a preparation of gonadotropins (FSH and LH activity), extracted from the urine of postmenopausal women, which has undergone additional steps for purification.” Each vial holds 75 IU of FSH activity and 75 IU of LH activity, measured by bioassays in rats (ovarian weight gain for FSH, seminal vesicle weight gain for LH), and the label adds that “Human Chorionic Gonadotropin (hCG) is detected in MENOPUR.” FSH and LH are glycoproteins (Menopur label): protein hormones, not short peptides.

Menotropins replaced animal hormones. Pregnant mare serum gonadotropin caused antibody formation and was withdrawn; human pituitary and urinary preparations followed. Bruno Lunenfeld writes that his group extracted hMG from postmenopausal urine in 1950, that Pietro Donini at Serono had also extracted it, and that Serono agreed to mass-produce it once old-age homes of nuns would provide the urine: about 300 women contributed, and the early preparations were only 5% pure. The product, Pergonal, was registered in Israel in 1963 and in Italy in 1965 (Lunenfeld, 2012). In the US, Drugs@FDA lists four menotropins: Pergonal (approved August 22, 1975), Humegon (1994), Repronex (1999) and Menopur (October 29, 2004). Only Menopur, from Ferring, is not listed as discontinued. Pergonal’s label also covered men: with hCG, it was indicated “for the stimulation of spermatogenesis in men who have primary or secondary hypogonadotropic hypogonadism” (Pergonal label, 1999 copy).

On March 23, 2020, all four applications were deemed biologics licenses, and FDA moved them from the Orange Book to the Purple Book (FDA list of deemed BLAs). Drugs@FDA now lists Menopur as BLA 021663, prescription only. FDA’s notice to compounders said these transitioning biologics are not eligible for the compounding exemptions in sections 503A and 503B, and named menotropins among four bulk substances outsourcing facilities had reported using.

Two analyses of what else is in the vial come from companies with competing gonadotropins. Authors writing from N.V. Organon (Organon USA held the FDA applications for Humegon and for Follistim, follitropin beta) found FSH, LH and hCG in Menopur, with hCG immunoactivity three times that of LH and at least 30% non-gonadotropin protein. They attributed about 95% of its LH-receptor activity in the body to hCG and wrote that, to the best of their knowledge, this much hCG can only be explained by hCG added from outside sources, “a well established practice for standardization purposes” (van de Weijer et al., 2003). A 2024 analysis funded by Merck KGaA, with Merck employees among its authors, tested five batches of Ferring’s highly purified hMG (three Menopur, two Menogon): the LH beta subunit appeared only in traces (0.9–1.2%) against 18–47% beta hCG of placental type, with 20–30% protein impurities and more than 200 non-gonadotropin proteins (Capolupo et al., 2024). Merck KGaA is running a Phase 3 of its own follitropin alfa/lutropin alfa against hMG (NCT07340827). A 2005 comparison whose first author was at Instituto Massone, Buenos Aires, found Menopur’s batch-to-batch consistency similar to that of recombinant FSH (Wolfenson et al., 2005).

PubMed indexes 3,230 records under the MeSH term Menotropins, 340 of them tagged as randomized controlled trials (searched September 29, 2026).

Mechanism of Action

HMG supplies the activity of the two pituitary gonadotropins, FSH and LH, that drive the testes and ovaries. The receptors below are named as the cited papers name them.

• FSH → FSH receptor (FSHR) — A G protein-coupled membrane receptor expressed in the Sertoli cells of the testes and the granulosa cells of the ovaries (Oduwole et al., 2021). The joint action of testosterone and FSH is exerted on Sertoli cells, which line the seminiferous tubules and support germ cells as they develop into sperm (Oduwole et al., 2021).
• LH and hCG → LH receptor (LHCGR) — Expressed in the Leydig cells of the testes and the thecal and luteal cells of the ovaries; LH controls testosterone production by Leydig cells, and hCG, made by the placenta and homologous to LH, acts on the same receptor (Oduwole et al., 2021).
• Both hormones for full sperm output — A review of testicular endocrinology concludes that both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species (Ramaswamy & Weinbauer, 2014).
• Where HMG’s LH activity comes from — The label says hCG is detected in Menopur. Two analyses by competing manufacturers trace most of its LH-type activity to hCG rather than LH (van de Weijer et al., 2003; Capolupo et al., 2024).
• In the ovary (the label) — Given for 7 to 20 days, Menopur “produces ovarian follicular growth and maturation in women who do not have primary ovarian failure”; when the follicles are mature, hCG must be given to induce ovulation (Menopur label).
• Why FSH is added in some men — In the 1985 NEJM study, hCG alone brought sperm counts to normal in all 6 men whose deficiency began after puberty but in 1 of 15 whose deficiency began before it; the authors concluded that the need for hMG “appears to depend on the time of onset of hypogonadism” (Finkel et al., 1985). hCG without FSH can complete sperm production in men with partial deficiency, and the response is predicted by testicular size at the start (Burris et al., 1988).
• Two brands differ in the dish — Menopur and another hMG, Meriofert, differ in their FSH:hCG ratio, and Menopur also contains LH molecules. In cells they differed in cAMP and β-arrestin 2 responses and in progesterone and estradiol output. The authors say the findings “require cautious interpretation and further validation from clinical studies” (Casarini et al., 2020).
• Pharmacokinetics — After repeated doses, FSH’s elimination half-life was 11–13 hours whether Menopur was injected under the skin or into the muscle, and the subcutaneous route “trends toward greater bioavailability” (Menopur label).

What the Research Shows

HMG has two bodies of human evidence: randomized trials in women for the label’s use, and mostly retrospective or uncontrolled series in men with hypogonadotropic hypogonadism.

• Egg development in IVF (the label’s use) — Three large randomized trials, each of more than 700 women, found highly purified hMG non-inferior to recombinant FSH on ongoing pregnancy (European and Israeli Study Group, 2002; Andersen et al., 2006; Devroey et al., 2012). The details are under Human Data.
• The 2026 Cochrane review — 59 randomized studies, 18,119 women. Against HMG or highly purified HMG, recombinant FSH probably gave fewer live births (odds ratio 0.83, 95% CI 0.73 to 0.95; 15 studies, 4,793 women) and probably more ovarian hyperstimulation syndrome (odds ratio 1.42, 95% CI 1.12 to 1.80; 37 studies, 9,813 women), both moderate-certainty evidence. “Many studies were sponsored by the pharmaceutical industry” (Berkhout et al., 2026).
• Sperm production in hormone-deficient men — A 2014 meta-analysis of 44 gonadotropin studies found an overall 75% success rate in bringing sperm into the semen, no difference between FSH preparations, and better results when hCG and FSH were used together; it concluded that gonadotropin therapy, “even with urinary derivatives,” is a suitable option (Rastrelli et al., 2014). A 2025 meta-analysis of 1,240 men found sperm returned faster with hCG plus hMG or recombinant FSH than with hCG alone (weighted mean 10 vs 33 months) and more often (66.76% vs 51.9%), with high heterogeneity (Pozzi et al., 2025).
• HMG or recombinant FSH, in men — In a retrospective study of 112 men given hCG first, 70 then received hMG and 42 recombinant FSH: 85.7% made sperm in both groups, and pregnancy rates of 38.6% and 51.2% did not differ significantly (Ortaç et al., 2020).
• Injections or a GnRH pump — In a study of 220 men its authors describe as randomized, sperm appeared in 62 men on a GnRH pump and 26 on hCG/HMG, and sooner with the pump (6.2 vs 10.9 months); the paper’s group sizes conflict between its sections, and its methods say the men were “voluntarily selected” for each therapy (Lin et al., 2019). In 28 men, not randomized, sperm appeared at a median 6 months with a gonadorelin pump and 14 months with hCG/HMG, in 90% and 83.3% (Zhang et al., 2019). In a retrospective study of 155 men, success rates did not differ (82.1% vs 75.8%), but the pump was faster (12.34 vs 14.74 months) (Zheng et al., 2025).
• What predicts success — Larger testes at the start predicted sperm or pregnancy in several series (Miyagawa et al., 2005; Farhat et al., 2010; Liu et al., 2016); undescended testes predicted a poorer or slower response (Finkel et al., 1985; Liu et al., 2016). On earlier testosterone therapy the findings disagree: no effect in two sources (Ley & Leonard, 1985; Rastrelli et al., 2014), lower peak sperm counts in one cohort (Shah et al., 2021).
• After anabolic steroids — One case report: a bodybuilder with no sperm a year after stopping steroids had normal semen analyses after 3 months of hCG and hMG (Menon, 2003). A 2023 narrative review lists hMG at 75–150 IU one to three times a week among “promising early pharmacologic approaches” for steroid users (Rizzuti et al., 2023). No trial in steroid users turned up in a PubMed search (September 29, 2026).

Human Data

Women, for the label’s use:

• European and Israeli Study Group, 2002 (the label’s trial) — Open-label, randomized, 22 centers in six countries, 781 women enrolled. 373 received highly purified hMG and 354 recombinant FSH. Ongoing pregnancy 10 weeks after egg retrieval, per protocol: 25% (85/344) and 22% (71/317); ovarian hyperstimulation, miscarriage, adverse events and injection-site reactions were similar (European and Israeli Study Group, 2002). The label reports the Menopur arm as 373 women with a continuing pregnancy rate of 23%, non-inferior to recombinant FSH (Menopur label).
• MERIT, 2006 — Randomized, assessor-blind, 731 women in IVF after a long GnRH agonist protocol. More eggs with recombinant FSH (11.8 vs 10.0), a higher share of top-quality embryos with hMG (11.3% vs 9.0%), ongoing pregnancy 27% vs 22% per cycle: non-inferiority established, superiority not (Andersen et al., 2006).
• MEGASET, 2012 (NCT00884221) — Randomized, assessor-blind, 749 women at 25 centers in seven countries, in a GnRH antagonist cycle with a single blastocyst transferred. Ongoing pregnancy after a fresh cycle 30% vs 27% per protocol; cumulative live birth 40% vs 38% (Devroey et al., 2012).

Men with hypogonadotropic hypogonadism, given HMG, nearly always with hCG:

• Finkel et al., 1985 (NEJM) — Of 14 men whose deficiency began before puberty and who did not reach normal counts on hCG, adding hMG brought counts to normal in 5 of 7 without undescended testes and 1 of 7 with them.
• Ley & Leonard, 1985 — 13 men, hCG followed in 12 by hMG: all but 1 had sperm in the semen on combined therapy; 2 men fathered three pregnancies. Earlier testosterone therapy made no difference to the response.
• Jones & Darne, 1993 — 9 men in whom hCG alone had failed self-injected hMG under the skin; 6 of 7 seeking fertility passed 10 million sperm/mL, with three pregnancies at the time of writing.
• Büchter et al., 1998 — 42 men, 57 treatment courses of hCG/hMG or pulsatile GnRH: sperm appeared in 54 of 57 courses and pregnancies followed in 26 of 36 courses aimed at them; hCG/hMG and GnRH did not differ significantly.
• Miyagawa et al., 2005 — 36 male patients aged 11 to 42, from 30 years of records, treated with hCG/hMG for 12 to 240 months (average 56): sperm in 36% of those with testes under 4 mL and 71% of those with larger testes.
• Farhat et al., 2010 — 87 married men, hCG/HMG into the muscle three times weekly for a median 26 months: 85 of 151 courses (56.3%) ended in pregnancy, 85 pregnancies in 35 men (40%).
• Liu et al., 2016 — 223 men with congenital deficiency and no sperm: 64% made sperm, at a median 15 months, with concentrations and motility below WHO standards; 19 of the 34 who wanted children fathered a pregnancy during treatment.
• Shah et al., 2021 — 35 men: after 33 ± 12 months, 70% made sperm; men with earlier testosterone therapy had lower peak counts (median 0.05 vs 9 million/mL).

A ClinicalTrials.gov search for menotropins as an intervention returned 12 studies with an active status on September 29, 2026, all enrolling women in fertility treatment. One is a US Phase 3 in which 659 women in IVF are to receive a human menopausal gonadotropin or placebo, with cumulative live birth as the primary outcome (Granata Bio; NCT07216742; estimated primary completion November 2028). No trial of HMG in men has an active status, and no trial of HMG taken alongside testosterone therapy turned up in a PubMed search on the same day.

The evidence meter on the HMG card reads “Approved drug” because Menopur is FDA-approved on the reproductive-hormone axis. That approval is for women in IVF; the men’s data above are the published record for men.

Reconstitution & Storage

Menopur comes as a freeze-dried powder, 75 IU of FSH and 75 IU of LH activity per vial, each vial paired with a 2 mL vial of sterile 0.9% sodium chloride and a Q•Cap vial adapter (Menopur label). The label reconstitutes it with that saline and names no other diluent. Its Instructions for Use: “The usual amount of 0.9% Sodium Chloride, USP used to mix your MENOPUR is 1 mL,” the vial is swirled, not shaken, and the same liquid can dissolve “up to 5 more vials,” so one injection can carry several vials. The label leaves the syringe and needle to the healthcare provider and does not specify an insulin syringe.

The table is arithmetic only, not a recommendation: how volume maps to IU for the amounts on this page (U-100 insulin syringe: 100 units = 1 mL), computed with the site’s calculator math.

• Storage before mixing — “Lyophilized powder may be stored refrigerated or at room temperature (3° to 25° C/37° to 77°F) until dispensed. Protect from light” (Menopur label).
• After mixing — “Use immediately after reconstitution. Discard unused material” (Menopur label). The label gives no storage time for mixed solution.
• Where it goes — Under the skin of the lower abdomen, 1–2 inches below the navel, alternating sides each day (Menopur Instructions for Use). Many men’s studies injected into the muscle (Liu et al., 2016; Lin et al., 2019; Farhat et al., 2010); one used self-injection under the skin (Jones & Darne, 1993).
• Other products — The Peking Union Medical College Hospital study mixed its hCG and HMG, both made in China, with 2 mL of sterile water for injection (Lin et al., 2019). A “research use only” vial is a different product; the catalog read for this page gives no storage temperature for it.

→ Peptide Calculator — vial-to-syringe math

Side Effects & Risks

Side effects from the label (women in IVF), the men’s studies and the composition analyses:

• Ovarian hyperstimulation syndrome (women) — In the label’s IVF trial it occurred in 7.2% of 373 women. It “may progress rapidly to become a serious medical event,” with fluid shifting into the abdomen, chest and sometimes the pericardium, and reaches its maximum about seven to ten days after treatment (Menopur label).
• Lung and blood-clot complications (women) — The label reports atelectasis, acute respiratory distress syndrome, asthma flares and thromboembolic events with gonadotropins; “In rare cases, pulmonary complications and/or thromboembolic reactions have resulted in death” (Menopur label).
• Multiple pregnancy (women) — 35.3% (30 of 85) of pregnancies in the label’s IVF trial were multiple (Menopur label).
• Common reactions (women) — In 434 women in two trials: abdominal pain 6.7%, headache 6.2%, ovarian hyperstimulation 6.2%, injection-site pain and reaction 3.9%, abdominal cramps 3.0%, enlarged abdomen 2.3%, injection-site inflammation 2.3%; thrombophlebitis in less than 1% (Menopur label).
• Pregnancy and allergy — Contraindicated in pregnancy (Category X) and after prior hypersensitivity to menotropins products (Menopur label).
• In men — In one comparison, the hCG/HMG group tended toward high testosterone, with more facial acne and breast tenderness than the pump group (Zhang et al., 2019). No patient in a 112-man study developed severe effects (Ortaç et al., 2020). In 13 men, PSA, prostate volume and testicular volume rose after 3 months of hCG/hMG (Ozata et al., 1997).
• What else is in the vial — Analyses by competing manufacturers put non-gonadotropin protein at 20–30% or more, with more than 200 proteins identified (van de Weijer et al., 2003; Capolupo et al., 2024).
• Research-chemical vials — At least one online catalog lists vials labeled “HMG,” 75 IU each, as “Research use only. Not for human consumption,” with “No reference files” linked to the entry. No document read for this page shows what is in them.
• Long-term — Carcinogenicity has not been studied in animals; ovarian neoplasms have been reported infrequently after multiple-drug ovarian stimulation, with no causal relationship established (Menopur label).
• WADA — The 2026 List does not name menotropins. It prohibits chorionic gonadotrophin and luteinizing hormone in males at all times (S2.2.1), and Menopur’s label lists LH activity and says hCG is detected in it.
• Drug interactions — “No drug/drug interaction studies in humans have been conducted for MENOPUR” (Menopur label).

Bloodwork & Monitoring

What the label and the studies describe:

• Women (label) — Ultrasound of follicle growth, with or without serum estradiol, to time the hCG trigger and catch ovarian enlargement; hCG is withheld when monitoring suggests a raised risk of hyperstimulation, and women are assessed for it for at least two weeks after hCG (Menopur label).
• Testosterone (men) — Measured 48 to 72 hours after an hCG injection, with hCG and HMG doses adjusted to hold it at 10–15 nmol/L in one study (Lin et al., 2019), and 2 days after hCG in another (Zhang et al., 2019).
• Semen and testes (men) — Semen analyses and testicular volume by Prader orchidometer at each visit: monthly in two studies (Jones & Darne, 1993; Lin et al., 2019), at 1 and 3 months and then every 3 months in another (Zhang et al., 2019), and every 3 to 6 months in the largest (Liu et al., 2016).
• PSA and prostate (men) — Both rose after 3 months of hCG/hMG in 13 men with hypogonadotropic hypogonadism (Ozata et al., 1997).
• Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

The combinations below are the ones the label and the studies use. No study of HMG taken together with testosterone therapy turned up in a PubMed search.

→ Peptide Calculator — vial-to-syringe math

Legal Status

Related Compounds

People researching HMG often also look at these:

Next Steps

References

1. Ferring Pharmaceuticals Inc. MENOPUR (menotropins for injection), for subcutaneous use. Prescribing Information, Patient Information and Instructions for Use (Rev. 05/2018; initial U.S. approval 1975). DailyMed, setid 22c8db95-c3db-1770-8086-31356fbabe35, SPL version 47, published May 11, 2026. dailymed.nlm.nih.gov. Read September 29, 2026.
2. U.S. Food and Drug Administration. Drugs@FDA records for menotropins: MENOPUR, BLA021663 (Ferring; prescription; approved October 29, 2004); REPRONEX, BLA021047; HUMEGON, BLA020328; PERGONAL, BLA017646 (all discontinued). api.fda.gov/drug/drugsfda.json. Read September 29, 2026.
3. Pergonal (menotropins for injection, USP) prescribing information, as reproduced in Mosby’s GenRx monograph “Menotropins” (copyright 1998) on RxList. Internet Archive copy of January 28, 1999: web.archive.org/web/19990128173144/http://www.rxlist.com/cgi/generic/menotropins.htm. Read September 29, 2026. (Indications and dosage for men.)
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40. Nexus Peptides. HMG catalog entry (SKU G75, 75iu × 10 vials, “Research use only”). nexuspeptides.it.com/en/shop/hmg. Read September 29, 2026.
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