hMG

What is hMG?

Human menopausal gonadotropin (hMG) is a purified preparation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity extracted from the urine of postmenopausal women, who excrete elevated gonadotropins as a consequence of ovarian failure. The original drug, Pergonal, was developed by Bruno Lunenfeld and Piero Donini in the late 1950s and remained for decades the only injectable gonadotropin available for treating infertility — used to induce ovulation in anovulatory women and to drive controlled ovarian stimulation for in vitro fertilization. Modern formulations (Menopur, Repronex, Menogon) are highly purified menotropins (HP-hMG) with reduced contaminating urinary proteins, dosed by FSH content with a labeled 1:1 ratio of FSH to LH activity (the LH activity in commercial Menopur is supplied substantially as hCG rather than native LH — the Menopur SmPC states that hCG obtained from the urine of pregnant women may be added to reach the required total LH bioactivity, so it is a deliberate addition from a different source material, not something co-purified from postmenopausal urine). hMG remains a clinically common alternative to recombinant FSH for ovarian stimulation, particularly in protocols where supplemental LH activity is considered desirable (older patients, hypogonadotropic hypogonadism, GnRH-antagonist cycles). In men, hMG is used adjunctively with hCG for fertility induction in hypogonadotropic hypogonadism when spermatogenesis fails to recover on hCG alone.

What hMG Is Investigated For

hMG has a single longstanding clinical center of gravity — gonadotropin-driven ovarian stimulation in assisted reproduction — and a smaller adjunctive role in male fertility induction. The strongest evidence is the IVF/ICSI literature: dozens of randomized trials and several meta-analyses comparing HP-hMG (Menopur) to recombinant FSH (Gonal-F, Follistim) in controlled ovarian stimulation, most recently synthesized in the 2026 Cochrane review by Berkhout and colleagues — the current authoritative reference for the choice-of-gonadotropin question in ART, and a result that modestly favours hMG. Across 59 studies and 18,119 women it concluded that live birth and clinical pregnancy are probably lower with recombinant FSH than with hMG/HP-hMG (live birth OR 0.83, 95% CI 0.73–0.95), while OHSS is probably higher with rFSH (OR 1.42, 95% CI 1.12–1.80), both at moderate certainty. Real-world and large-cohort work has extended that picture in both directions. A 2026 US claims analysis of 14,174 women found higher adjusted odds of live birth with HP-hMG-containing protocols than with follitropin alfa, while a 2026 series of 4,525 antagonist cycles found HP-hMG came last of three gonadotropins on antral-follicle-adjusted follicular recruitment and oocyte yield — fewer eggs, in other words, even where outcomes hold up. A 2026 randomized trial also established that a pre-filled hMG pen is non-inferior to the US powder formulation. The trade-off is reasonably well characterised. hMG produces fewer oocytes per cycle on average, but carries a small live-birth advantage per started cycle in the pooled data, produces lower serum progesterone on the day of trigger (potentially favouring fresh-transfer endometrial receptivity), and — on three independent 2025–2026 syntheses that now agree on direction — a lower risk of ovarian hyperstimulation syndrome than recombinant FSH. In the MEGASET-HR post hoc analysis of 620 high-AMH women, holding oocyte yield constant, the odds of early OHSS on HP-hMG were 0.46 times those on rFSH (95% CI 0.26–0.82). In men, hMG combined with hCG can rescue spermatogenesis in hypogonadotropic hypogonadism patients who do not achieve adequate sperm counts on hCG monotherapy — a smaller evidence base but a clinically established adjunctive use. The honest caveats: hMG is a urine-derived biological with batch-to-batch variability that recombinant FSH does not have, and the LH activity in modern Menopur is substantially provided by hCG added during manufacture from the urine of pregnant women, rather than by native LH (a distinction that matters mechanistically and for some interpretations of the FSH-vs-hMG comparison literature). hMG is not used for TRT, weight loss, or any non-fertility indication — those are different drugs (hCG, gonadorelin, GLP-1 agonists).

History & Discovery

The clinical history of hMG begins with the recognition in the 1930s and 1940s that postmenopausal women excrete elevated levels of gonadotropins — the consequence of ovarian failure removing the negative feedback that normally restrains pituitary FSH and LH secretion. In the late 1940s and early 1950s, the Italian chemist Piero Donini at the Serono Institute in Rome developed a method for extracting and purifying gonadotropins from postmenopausal urine, an industrial-scale concept that depended on collecting large volumes of urine — famously from postmenopausal nuns in Italian convents and old-age homes, an arrangement helped by the Vatican's substantial stake in Serono at the time. The clinical translation came through Bruno Lunenfeld, who had been extracting hMG with Borth and de Watteville in Geneva and who contacted Donini in 1957; their collaboration produced Pergonal, the first injectable hMG product. By Lunenfeld's own account the first successful induction of ovulation followed by pregnancy in hypogonadotropic anovulatory women came in 1961, with the first child delivered that same year and the work published in 1962 — beginning the modern era of gonadotropin-based fertility treatment. Pergonal was registered in Israel in 1963 and in Italy in 1965. Pergonal remained the standard for decades, used for ovulation induction in anovulatory women, controlled ovarian stimulation, and as one of the foundational drugs of early IVF following the first successful birth in 1978. Recombinant FSH (Gonal-F, follitropin alfa — EU marketing authorisation October 1995, US FDA approval September 1997; Follistim, follitropin beta) eventually offered a non-urine-derived, batch-consistent alternative, and the comparative literature between rFSH and hMG became one of the most studied questions in reproductive endocrinology. In parallel, urinary preparations were progressively purified — moving from Pergonal (relatively crude) to highly purified menotropin products like Menopur (Ferring, US approval October 2004) with substantially reduced contaminating urinary proteins and SC-injection compatibility. Menopur became the dominant modern hMG formulation, often dosed alongside rFSH or as a standalone gonadotropin in IVF cycles, particularly in protocols where supplemental LH activity is considered advantageous (older patients, hypogonadotropic hypogonadism, GnRH-antagonist cycles). In male reproduction, the discovery in the 1970s and 1980s that combined hCG (LH-mimetic) plus hMG (FSH + LH activity) could induce spermatogenesis in hypogonadotropic hypogonadism patients established hMG's adjunctive role in male fertility, where hCG monotherapy is the first-line approach but hMG is added when sperm counts remain inadequate. This combined-gonadotropin protocol remains the standard for fertility induction in male hypogonadotropic hypogonadism today.

How It Works

hMG provides the body with the two hormones (FSH and LH) that normally drive ovulation. By giving these as injections, doctors can encourage the ovaries to develop multiple eggs at once during IVF treatment, or to ovulate in women who don't ovulate on their own.

hMG supplies exogenous gonadotropic activity that mimics endogenous pituitary FSH and LH. FSH binds FSH receptors on ovarian granulosa cells, driving recruitment, growth, and selection of follicles, granulosa-cell proliferation, aromatase induction, and estradiol production. LH activity (via the LHCGR shared with hCG) binds theca cells to produce androgen substrate for aromatization, supports late-follicular maturation, and contributes to the final follicular environment. In men, the same dual FSH/LH signal supports both Sertoli-cell function (FSH-driven spermatogenesis) and Leydig-cell testosterone production (LH-driven), which is why combined hMG + hCG can produce spermatogenesis in hypogonadotropic men where hCG alone has been insufficient. A mechanistically important detail: in modern HP-hMG products (notably Menopur), the LH activity is supplied substantially as hCG rather than native pituitary LH — and that hCG is added during manufacture, sourced from the urine of pregnant women, rather than co-purified along with the FSH from postmenopausal urine. hCG and LH bind the same receptor but with different pharmacokinetics — hCG has a 24–36 hour half-life vs. minutes for LH — which contributes to a more sustained LH-receptor stimulus per dose. Trigger-day serum progesterone is consistently lower with hMG than with rFSH, attributed to a shift in granulosa-cell steroidogenesis from the Δ5 (pregnenolone → progesterone) toward the Δ4 pathway (pregnenolone → androstenedione), an effect of the hCG-driven LH activity on follicular steroid output.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about hMG:

• 01Optimal patient subgroups for hMG vs. recombinant FSH — meta-analyses have generally not identified universal superiority, but specific subgroups (older patients, expected high responders, hypogonadotropic patients) where hMG has greater advantage continue to be characterized.
• 02Mechanism of lower trigger-day progesterone with hMG — recent steroidogenesis-pathway analyses (Δ4 vs Δ5 shift) provide a mechanistic story, but its clinical impact on live birth rates in fresh-transfer cycles is not fully resolved.
• 03Differential OHSS risk — the direction is now reasonably settled (the 2026 Cochrane review, the Espinós 2026 meta-analysis of 56 RCTs, and the MEGASET-HR post hoc analysis all point to lower OHSS with LH-active gonadotropins than with rFSH), but the magnitude in unselected populations, and whether it survives modern freeze-all and GnRH-agonist-trigger practice that already suppresses OHSS, remains to be quantified prospectively.
• 04Long-term oncologic safety after repeated stimulation cycles — broadly reassuring evidence exists but very long-duration follow-up of patients exposed to multiple cycles in modern IVF practice continues to be characterized.
• 05Optimal LH-supplementation strategy across protocols — whether the LH activity in hMG is best replicated by recombinant LH preparations, native hCG-driven LH activity, or co-administration with rFSH remains an active question in protocol design.
• 06Adjunctive use in male fertility induction — combined hCG + hMG is established for hypogonadotropic hypogonadism, but optimal dose, duration, and patient selection are not standardized across centers.

Forms & Administration

Subcutaneous injection of reconstituted lyophilized powder. The US Menopur label specifies subcutaneous administration into the abdomen, and the UK SmPC is explicit that it is for subcutaneous use only — intramuscular administration appears in older pharmacokinetic work but is not the labelled route in the US, EU or Canada. In the United States Menopur is supplied in a single strength, a 75 IU vial (75 IU FSH plus 75 IU LH activity) packaged with 0.9% sodium chloride diluent; the 1200 IU multi-dose vial is a non-US presentation. The US label sets a starting dose of 225 IU/day with adjustments no sooner than five days apart, by no more than 150 IU at a time, and a ceiling of 450 IU/day. All injectable peptides should only be administered under the guidance of a qualified healthcare provider. Never self-administer without clinician oversight.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

hMG is FDA-approved for ovulation induction and assisted reproduction under clinician supervision. It is not appropriate for self-directed use, performance enhancement, weight loss, or any non-fertility application. Its safety depends on appropriate monitoring throughout the stimulation cycle.

Timeline of Effects

Monitoring & Measurement

Common Questions

Who hMG Is NOT For

Drug & Supplement Interactions

hMG has a relatively limited drug-interaction profile because its action is on specific gonadotropin receptors with a defined endocrine pathway. Concurrent GnRH agonists (leuprolide, triptorelin) and GnRH antagonists (cetrorelix, ganirelix) are used in combination by design to control endogenous LH surges during IVF stimulation, and hMG dosing is calibrated against these protocol elements. For patients with PCOS undergoing combination protocols with letrozole or clomiphene, the addition of hMG to oral ovulation-induction agents is a recognized escalation strategy when monotherapy has not achieved ovulation. Recent network meta-analyses have characterized clinical pregnancy rates with various combinations. Concurrent androgens or estrogens that affect hypothalamic-pituitary feedback can theoretically alter response, but most fertility patients are not on such agents. Tamoxifen and aromatase inhibitors used in oncology contexts have specific interactions with ovarian stimulation that fall outside routine hMG use. Patients on corticosteroids for autoimmune indications should generally continue them through stimulation cycles under specialist guidance. As always, full medication disclosure to the fertility specialist before initiating gonadotropin therapy is essential.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions