HMG
Also known as: Menopur, Pergonal, Humegon, Repronex, Human Menopausal Gonadotropin, Menotropins, hMG
Evidence: Clinical
Overview
Urine-derived menotropins with FSH and LH activity; Menopur (2004) is the only marketed US product, labeled for follicle development in IVF. Pergonal, Humegon and Repronex are discontinued.
Human menopausal gonadotropin (menotropins) is extracted and purified from the urine of postmenopausal women and carries FSH and LH activity; Menopur vials hold 75 IU of each, and hCG is detectable in the product. Pergonal, the first menotropin, was approved in the US in 1975 and is discontinued, as are Humegon and Repronex. Menopur (BLA 021663, 2004) is the only marketed US menotropin, labeled for development of multiple follicles and pregnancy in ovulatory women as part of assisted reproduction. None of these products is recombinant. Vendor research vials are not the labeled product.
Benefits
Multiple follicle development and pregnancy in women undergoing IVF (FDA-labeled; RCTs non-inferior to recombinant FSH), spermatogenesis induction in men (historic use, not a current US indication)
Dosing reference
- Research dose
- Community range 75 to 150 IU daily. The Menopur label regimen (ART in women) is in the dosing notes.
- Reconstitution
- 1 mL bacteriostatic water
- Common vial sizes
- 75 mg, 150 mg
Menopur label (ART in women), SC: starting dose 225 IU per day for the first cycle; adjust after 5 days by no more than 150 IU at a time; no more than 450 IU per day; stimulation up to 20 days in the pivotal trial. The 75 to 150 IU daily range in this record does not match the current US label, and no current US label covers men.
Mechanism
Menotropins supply FSH, which drives growth and maturation of ovarian follicles, and LH activity, which supports follicular steroid production. Given for 7 to 20 days to women without primary ovarian failure, Menopur produces follicular growth and maturation but usually not ovulation; hCG is then needed to trigger it (Menopur label). In men, FSH acts on Sertoli cells to support spermatogenesis and LH on Leydig cells to make testosterone. Menopur and Pergonal are urinary extracts, not recombinant proteins (Menopur label; Lunenfeld 2004).
Evidence
Clinical: at least one published human trial or an approved drug
- Highly purified hMG versus recombinant FSH in IVF after GnRH agonist suppression: ongoing pregnancy rates non-inferior (MERIT, Andersen et al., 2006); the label reports 23% continuing pregnancy in 373 Menopur patients
- Highly purified hMG versus recombinant FSH in a GnRH antagonist cycle with single-blastocyst transfer (MEGASET, Devroey et al., 2012)
- Historical account of urinary gonadotropins from Pergonal onward (Lunenfeld, 2004)
- Human-trial status: approved by the FDA as Menopur (BLA 021663, 2004) for multiple follicle development in ART, marketed; Pergonal (1975), Humegon (1994) and Repronex (1999) are discontinued; no current US label covers men
References
- Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Andersen AN, Devroey P, Arce JC, Human Reproduction, 2006
- A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Devroey P, Pellicer A, Nyboe Andersen A, Arce JC, Fertility and Sterility, 2012
- Historical perspectives in gonadotrophin therapy. Lunenfeld B, Human Reproduction Update, 2004
Side effects
Menopur label: abdominal pain, cramps and enlargement, headache, injection-site pain and inflammation, and OHSS were the most common. Serious: abnormal ovarian enlargement, ovarian hyperstimulation syndrome, ovarian torsion, atelectasis or respiratory distress, thromboembolic events, multi-fetal gestation, ectopic pregnancy, spontaneous abortion, congenital malformations and ovarian neoplasms.
Storage
- Storage
- Powder: 3 to 25°C, refrigerated or room temperature, protected from light (Menopur label)
- Lyophilized
- 24+ months at room temperature
- Reconstituted
- Use immediately after reconstitution; discard unused material (Menopur label)
Pharmacology
- Half-life
- FSH elimination half-life 11 to 13 h after multiple SC or IM doses in pituitary-suppressed women (Menopur label); LH half-life not reported
- Bioavailability
- SC trends toward higher exposure than IM: single 225 IU dose FSH AUC 726 vs 656 h·mIU/mL in 33 healthy women (Menopur label). Absolute bioavailability not reported.