Hormonal & Sexual

HMG

Human Menopausal Gonadotropin

Human menopausal gonadotropin (hMG) is a hormone mixture used in fertility research to stimulate ovarian follicle development and ovulation. It provides FSH and LH activity and is studied in assisted reproduction and hypogonadotropic hypogonadism.

hMG

Human Menopausal Gonadotropin
Gonadotropin
FDA Approved

Half-Life

Not established

Route

Subcutaneous (SC) or intramuscular (IM); SC preferred

Typical Dose

150–450 IU daily for IVF; 75 IU daily for ovulation induction

Mechanism / Target

FSH and LH/hCG receptors on ovarian cells

Evidence Level

High (multiple RCTs, meta-analyses)

Primary Research Use

Controlled ovarian stimulation for IVF and ovulation induction

Mechanism: Supplies FSH to drive follicle growth and LH activity to support maturation, enabling multi-follicular development and ovulation.

This information is for research only. Not intended for human use.

Overview

Human menopausal gonadotropin (hMG, menotropins) is a hormone mixture derived from the urine of postmenopausal women. It provides follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity, essential for ovarian follicle growth and ovulation . Highly purified preparations (HP-hMG) are standardized at 75 IU of FSH per vial and also contain hCG, which contributes LH-like effects .

In fertility research, hMG is primarily used for ovarian stimulation in IVF, where it supports the development of multiple follicles to retrieve eggs . It is also studied for ovulation induction in women with polycystic ovary syndrome (PCOS) or low pituitary hormone levels (hypogonadotropic hypogonadism) . In men, combined with hCG, hMG can restart sperm production when the pituitary fails to send enough signals .

Large meta-analyses show that hMG achieves similar live birth rates to recombinant FSH while possibly offering a lower risk of ovarian hyperstimulation syndrome (OHSS) . Modern formulations can be injected under the skin and are available as ready-to-use pre-filled pens that are as effective as traditional powders .

How it works

hMG works by directly activating the receptors for FSH and LH on ovarian cells. FSH binds to granulosa cells, stimulating follicle growth and the conversion of androgens to estrogens . LH and hCG both attach to a shared receptor on theca and granulosa cells, which boosts androgen production and supports the later stages of follicle maturation and ovulation .

The hCG component in hMG has a longer half-life than pituitary LH, providing sustained LH-like activity. This may help fine-tune ovarian response and contribute to the lower OHSS risk seen with hMG in some studies .

In simple terms, hMG replaces the natural FSH and LH signals that the pituitary would send, allowing researchers to control the number and timing of follicle development.

Documented effects

The primary effect of hMG in women is the growth of multiple ovarian follicles containing mature eggs, essential for IVF egg retrieval . In ovulation induction, it can produce a single mature follicle for timed intercourse or insemination . In men, long-term hMG combined with hCG can restore sperm production in hypogonadotropic hypogonadism, with sperm appearing in the ejaculate in about three-quarters of cases after 6–24 months of treatment .

The most serious adverse effect is ovarian hyperstimulation syndrome (OHSS), where the ovaries rapidly enlarge, fluid leaks from blood vessels, and in severe cases, blood clots or kidney failure can occur . Research suggests hMG is associated with a lower OHSS risk than recombinant FSH alone, especially in high-risk patients . Common side effects include injection site reactions (less with highly purified preparations) , headache, and abdominal bloating .

Research protocols

In fertility research, hMG administration is carefully tailored using ultrasound and blood tests. Typical IVF stimulation protocols begin with 150–225 IU injected subcutaneously daily for 10–14 days, with dose adjustments based on follicle growth and estrogen levels . For ovulation induction in PCOS, a low-dose step-up approach starts at 75 IU and increases by 37.5 IU every 5–7 days until a dominant follicle develops .

Monitoring is critical: transvaginal ultrasound measures follicle size and number, while blood estradiol tracks ovarian response . The goal is to balance the chance of pregnancy against the risk of OHSS; if many follicles develop, a freeze-all strategy or a lower trigger dose may be used . The interactive protocol timeline below illustrates a common ovulation induction regimen.

hMGSubcutaneous
1

Low-dose start

75 IUOnce daily5–7 days

Monitor follicle growth. If no response, step up.

2

First increase

112.5 IUOnce daily5–7 days

Continue monitoring. Increase further if needed.

3

Second increase

150 IUOnce dailyUntil dominant follicle ≥18 mm (typically 2–5 days)

Trigger ovulation when mature follicle present.

This information is for research only. Not intended for human use.

Reconstitution and storage

hMG is supplied as a sterile lyophilized powder requiring reconstitution. Typically, a 75 IU vial is mixed with 1 mL of 0.9% sodium chloride diluent provided by the manufacturer . The diluent is added gently, and the vial is swirled (not shaken) until the powder dissolves completely, forming a clear solution.

Once reconstituted, the solution must be used immediately; any unused portion is discarded because it contains no preservatives . Unmixed vials are stored at room temperature (15–30°C) away from light. A pre-filled liquid pen formulation is also available, which eliminates the mixing step . Use the calculator below to explore how vial size, diluent volume, and desired dose relate.

IU
ml
IU

Concentration

0.75 IU / unit

Draw Volume

100 units (1 ml)

Doses Per Vial

1 doses

Total Solution

100 units (1 ml)

This information is for research only. Not intended for human use.

Interactions

In ovarian stimulation research, hMG is almost always combined with other medications. GnRH antagonists or agonists are used to block premature ovulation, allowing controlled follicle growth . A final triggering injection of hCG is often used to induce egg maturation, but this raises OHSS risk when many follicles are present .

Oral agents like clomiphene citrate or letrozole are sometimes added to lower the hMG dose needed, especially in poor responders . Non-steroidal anti-inflammatory drugs (NSAIDs) have been studied to prevent premature ovulation, but their routine use is not standard . Animal studies suggest that high-dose green tea extract (EGCG) may impair uterine blood vessel development, so caution with concentrated supplements is advised during hMG protocols .

Stacking

hMG is frequently stacked with other hormones to enhance fertility outcomes. In IVF, it is commonly paired with hCG to trigger ovulation or provide luteal phase support . Adding growth hormone in poor responders has shown increased egg numbers and more embryos for transfer . In men, hMG is combined with hCG to stimulate both testosterone and sperm production, a proven strategy for restoring fertility in hypogonadotropic hypogonadism .

Some protocols stack oral medications like clomiphene or letrozole with low-dose hMG to improve ovarian response while minimizing total gonadotropin exposure . These combinations are tailored to individual ovarian reserve and response patterns.

Regulatory status

Highly purified human menopausal gonadotropin (Menopur®) is FDA-approved for ovarian stimulation and ovulation induction, available as both powder and pre-filled pen . It requires a prescription and is not a controlled substance. Internationally, it is approved in Europe, the UK, Australia, and many other countries.

The World Anti-Doping Agency (WADA) prohibits hMG in all athletes at all times under category S2.2 (Gonadotrophins), as it can indirectly increase testosterone production.

Safety and side effects

The most critical risk is ovarian hyperstimulation syndrome, which can vary from mild bloating to life-threatening blood clots and kidney failure . Some studies suggest hMG carries a lower OHSS risk than recombinant FSH alone . Common side effects include injection site discomfort (reduced with highly purified formulations) , headache, and abdominal bloating . Rarer complications include ovarian torsion and thromboembolism.

hMG should only be used under specialist supervision with regular ultrasound and blood monitoring. It is contraindicated in pregnancy, hormone-sensitive cancers, and unexplained vaginal bleeding. Long-term cancer risk after multiple cycles is not fully established.

Frequently asked questions

Is hMG FDA-approved?+

Evidence level: randomized controlled trial (non-inferiority study)

Yes. Highly purified human menopausal gonadotropin (HP‑hMG; Menopur®) is FDA‑approved for ovarian stimulation in women undergoing infertility treatment. A 2026 trial confirmed that the pre‑filled pen formulation is non‑inferior to the US‑approved powder for the number of fertilized oocytes, and a ready‑to‑use liquid pen provides bioequivalent FSH exposure to powder.

How is hMG administered?+

Evidence level: community protocol

hMG is injected subcutaneously, either as a reconstituted powder or via a pre‑filled pen. The pen delivers the same efficacy as the powder with fewer injection‑site reactions and greater convenience (community protocol). Intramuscular administration is also possible but less common. Typical daily doses range from 75 IU to 450 IU depending on ovarian reserve and response, with stimulation usually lasting 9–13 days.

How does hMG compare to recombinant FSH?+

Evidence level: meta-analysis of RCTs and clinical guideline

A large 2026 meta‑analysis (56 RCTs, 14,034 women) showed that LH‑containing gonadotropins (including hMG) result in little to no difference in live birth rate or ongoing pregnancy rate compared with recombinant FSH (rFSH) alone. hMG retrieves a slightly lower number of oocytes (mean difference –0.50) but probably does not increase the risk of ovarian hyperstimulation syndrome (OHSS) (RR 0.80, 95% CI 0.61–1.03; moderate certainty). The ESHRE 2025 guideline acknowledges that hMG is a suitable alternative to rFSH, particularly when LH activity is clinically desirable.

Can hMG be used for male infertility?+

Evidence level: cohort study and randomized controlled trial

Yes. In men with hypogonadotropic hypogonadism (HH) and non‑obstructive azoospermia, combined hCG/hMG therapy can induce spermatogenesis. A 2026 cohort of 35 HH‑related azoospermic men treated with hCG ± rFSH/hMG for a mean of 12 months reported sperm appearance in the ejaculate in 77%, and microTESE retrieved sperm in 88% of persistent azoospermia. In male adolescents with congenital HH, hCG/hMG was as effective as a GnRH pump in promoting puberty and testicular growth, with sustained spermatogenesis over 12 months.

What is the risk of OHSS with hMG?+

Evidence level: meta-analysis of RCTs and guideline

hMG carries a lower risk of moderate/severe OHSS than rFSH‑only stimulation. In the meta‑analysis, the pooled RR for OHSS was 0.80 (95% CI 0.61–1.03; moderate certainty) favoring LH‑containing gonadotropins. ESHRE guidelines recommend considering LH activity (as provided by hMG) in predicted high responders as part of a freeze‑all strategy to reduce OHSS risk.

How should hMG be stored?+

Evidence level: community protocol

Unreconstituted hMG powder should be stored at room temperature (20–25°C). After reconstitution, the solution must be used immediately; discard any unused portion (community protocol). The newer liquid‑formulation pre‑filled pen does not require refrigeration and remains stable at room temperature. Always check the specific product labeling for exact storage conditions.

References

  1. 1.Human menopausal gonadotrophin in a pre-filled injection pen is non-inferior to the US-approved powder formulationWitz, et al. · 2026
  2. 2.Comparing clinical outcomes of rFSH versus rFSH+HP-hMG in women undergoing in vitro fertilization-embryo transfer in real‑world practice: a retrospective studyKim, et al. · 2026
  3. 3.Comparative Effectiveness of Follitropin Delta, Follitropin Alpha, and <scp>hMG</scp> in <scp>ART</scp> Cycles: A Single‐Center Retrospective Cohort Study With Propensity Score MatchingEnatsu, et al. · 2026
  4. 4.Quantitative determination of trace principal components with high specific activity in menotropinsSun, et al. · 2026
  5. 5.Reverse-Phase High-Performance Liquid Chromatography/Mass Spectrometry (RP-LC-MS/MS, Label-Free Method) for Component Analysis of Gonadotropin DrugsHuang, et al. · 2026
  6. 6.Luteinizing hormone activity in ovarian stimulation: comparative efficacy and safety of gonadotropins versus recombinant follicle-stimulating hormone-a systematic review and meta-analysisEspinós, et al. · 2026
  7. 7.ESHRE guideline: ovarian stimulation for IVF/ICSI: an update in 2025†Unknown, et al. · 2026
  8. 8.Comparative Effectiveness of Recombinant Human Follicle-Stimulating Hormone:Recombinant Human Luteinizing Hormone in a 2:1 Ratio versus Highly Purified Human Menopausal Gonadotropin Alone in Ovarian Stimulation for Medically Assisted Reproduction Treatment Using in vitro Fertilization/Intracytoplasmic Sperm Injection: A Systematic Review and Meta-AnalysisDahan, et al. · 2026
  9. 9.Fertility Outcomes in Men with Nonobstructive Azoospermia Due to Hypogonadotropic Hypogonadism After Gonadotropin TherapyZachariou, et al. · 2026
  10. 10.Efficacy of sequential letrozole and gonadotropin therapy for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysisSajjad, et al. · 2025
  11. 11.Gonadotropins for ovulation induction in women with polycystic ovary syndromeWeiss, et al. · 2025
  12. 12.Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadismLiu, et al. · 2021
  13. 13.Highly purified human menotropin (HP-hMG) is associated with a low incidence of ovarian hyperstimulation syndrome (OHSS) in patients undergoing in vitro fertilization: menopur in gnrh antagonist single embryo transfer - high responder (MEGASET-HR) trial outcomesHeiser, et al. · 2018
  14. 14.The effects of low‐dose human chorionic gonadotropin combined with human menopausal gonadotropin protocol on women with hypogonadotropic hypogonadism undergoing ovarian stimulation for in vitro fertilizationJiang, et al. · 2017
  15. 15.Highly Purified Human Menopausal Gonadotropin (Menopur®): A Profile of Its Use in InfertilityDeeks · 2018
  16. 16.The ovulation trigger method affects gonadotropin concentrations and gonadotropin receptor expression during final oocyte maturation in womenPoulsen, et al. · 2026
  17. 17.P–587 Highly purified human menopausal gonadotrophin (HP-hMG, Menopur) as a ready-to-use solution for injection in pre-filled pen is bioequivalent to HP-hMG powder for reconstitutionJonker, et al. · 2021
  18. 18.Safety evaluation of a novel progesterone vaginal ring (PVR) for luteal phase support: SARA trialStadtmauer, et al. · 2026
  19. 19.Transdermal testosterone gel vs placebo in women with diminished ovarian reserve prior to in vitro fertilization: a randomized, clinical trialPolyzos, et al. · 2026
  20. 20.Optimizing mature oocyte yield in IVF: clinical comparison of r-hFSH+r-hLH and hMG in women with a stimulation dosage of at least 300 IU of gonadotropinsFatemi, et al. · 2026
  21. 21.Luteinizing hormone supplementation with human menopausal gonadotropin versus low dose human chorionic gonadotropin during ovarian stimulation does not affect live birth rates after fresh and frozen embryo transferFischer, et al. · 2024
  22. 22.Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 casesBuchter, et al. · 1998
  23. 23.Combined Human Chorionic Gonadotropin (HCG) and Human Menopausal Gonadotropin (hMG) Treatment in Gonadotropin‐Deficient Males with Pituitary DwarfismTanaka, et al. · 1992
  24. 24.Subcutaneously administered Menopur(R), a new highly purified human menopausal gonadotropin, causes significantly fewer injection site reactions than Repronex(R) in subjects undergoing in vitro fertilizationKeye, et al. · 2005
  25. 25.LH supplementation in ovarian stimulation: propensity score and generalized estimating equations analysis over 2000 embryosDizdar, et al. · 2026
  26. 26.Impact of fertility treatments on headache disorders: a systematic review with an overview of treatment modalitiesHoehne, et al. · 2026
  27. 27.Pre-trigger risk scoring for moderate-to-severe ovarian hyperstimulation syndrome in in vitro fertilization and intracytoplasmic sperm injection cyclesHe, et al. · 2026
  28. 28.Ovarian hyperstimulation syndrome with pleural effusion after unassisted pregnancy during a luteal-phase stimulation cycleEmole, et al. · 2026
  29. 29.Human menopausal gonadotropin-induced bioprosthetic valve thrombosisAbazid, et al. · 2018
  30. 30.Association Between Diclofenac Sodium Use and Reduced Cycle Cancellation from Premature Ovulation in Women with Diminished Ovarian Reserve Undergoing IVF: A Retrospective Cohort StudySong, et al. · 2026
  31. 31.The Effect of Indomethacin on Spontaneous and human Menopausal Gonadotropin Induced Pressure changes in the tissue and arterial vascular system from Human Ovaries Perfused in vitroSpätling, et al. · 1982
  32. 32.Evaluation of Endometrial Angiogenesis in Mice Uterus Before Implantation in Natural Cycles Followed by Use of Human Menopausal Gonadotropin - Human Chorionic Gonadotropin Drugs and Epigallocatechin GallateRashidi, et al. · 2017
  33. 33.Effect of growth hormone adjuvant treatment on oocyte retrieval in patients with poor ovarian response and no viable embryos in previous <i>in vitro</i> fertilization (IVF) cyclesGao, et al. · 2026
  34. 34.Can We Improve Pregnancy Rates in Hormone Receptor-Positive Breast Cancer After Endocrine Therapy? The Role of Fertility Preservation Beyond Gonadotoxic TherapyLuciani, et al. · 2025
  35. 35.Effectiveness of minimal stimulation versus conventional GnRH antagonist protocols in controlled ovarian hyperstimulation: a retrospective analysis of 10769 IVF/ICSI cyclesSANAGOUDAR, et al. · 2026
  36. 36.Addition of Clomiphene Citrate to a Low-Dose Gonadotropin-Releasing Hormone (GnRH)-Antagonist Protocol in Poor Responders: A Prospective Cohort StudyTriantafyllidou, et al. · 2026
  37. 37.Letrozole Co-Administration in Progestin-Primed Ovarian Stimulation (PPOS) Protocols for Patients Undergoing In Vitro Fertilization: A Systematic ReviewDi Girolamo, et al. · 2026
  38. 38.Medroxyprogesterone acetate vs. GnRH antagonist for preventing premature LH surge during ovarian stimulation in assisted reproductive technology: a retrospective cohort studyJimenez, et al. · 2026
  39. 39.IgA Vasculitis With Nephritis Following Controlled Ovarian Stimulation and Oocyte DonationBrader, et al. · 2025
  40. 40.A drop in serum estradiol levels during GnRH antagonist cotreatment in cycles stimulated with gonadotropins is associated with lower cumulative live birth ratesJanssens, et al. · 2026
  41. 41.Assessment indicators of ovarian response during controlled ovarian stimulation: influencing factors and clinical valueXu, et al. · 2026
  42. 42.Efficacy and safety of different cetrorelix doses in the luteal phase for preventing ovarian hyperstimulation syndrome: A cross-sectional studyMoghaddam, et al. · 2026
  43. 43.Dual Impact of Estradiol Fluctuations in the Final Three Days on IVF/ICSI Outcomes: A Retrospective Cohort AnalysisXiao, et al. · 2025
  44. 44.Association between menstrual cycle length and ovarian reserve markers and stimulation response: a retrospective cohort studyAykanat, et al. · 2026
  45. 45.Alterations in the ultrasound appearance of seminiferous tubules after gonadotropin treatment in patients with azoospermia because of hypogonadotropic hypogonadismNariyoshi, et al. · 2025
  46. 46.Impact of ovarian stimulation duration in GnRH antagonist protocols on the cumulative ongoing pregnancy rate in women with normal ovarian reserve: a cohort studyCohen Aloro, et al. · 2026
  47. 47.First pre-filled pen device with highly purified human menopausal gonadotropin (HP-hMG, Menopur) in liquid is shown to be bioequivalent to powder for reconstitutionJonker, et al. · 2021
  48. 48.Analysis of Nurse and Patient Preferences for Pre-Filled Pen Devices for Self-Injection of Highly Purified Human Menopausal Gonadotropin (HP-hMG, MENOPUR(®))De Mesmaeker, et al. · 2023

Last reviewed on Jun 25, 2026

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