Human Menopausal Gonadotropin

Overview

Human menopausal gonadotropin (HMG), generically known as menotropin, is a gonadotropin preparation purified from the urine of postmenopausal women. It contains both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity in approximately equal ratios by International Units, along with minor amounts of other urinary glycoproteins.

HMG preparations were introduced in the 1950s and 1960s as the first practical source of injectable FSH/LH activity for fertility research and clinical application. The rationale is straightforward: postmenopausal women have chronically elevated pituitary gonadotropin output due to the loss of ovarian negative feedback, and this surplus is excreted in urine where it can be concentrated and purified.

Modern HMG has largely been supplemented, and in many protocols replaced, by highly purified urinary FSH and recombinant FSH/LH, though HMG remains in use where combined FSH/LH activity at a fixed ratio is preferred. In peptide catalogs, HMG is included because it is a glycoprotein peptide hormone preparation used across several categories of fertility research.

Structure / Chemistry

HMG contains two principal heterodimeric glycoprotein hormones:

• FSH (follicle-stimulating hormone): alpha and beta subunits, approximately 35 kDa glycoprotein
• LH (luteinizing hormone): alpha and beta subunits, approximately 30 kDa glycoprotein; menopausal urinary material often includes human chorionic gonadotropin (hCG) contributing to LH activity

Both FSH and LH share an identical alpha subunit, with differentiation conferred by hormone-specific beta subunits. Glycosylation patterns of urinary material differ slightly from pituitary-native or recombinant forms, influencing half-life and receptor pharmacology. HMG preparations are standardized in International Units of FSH and LH activity, typically presented at a 1:1 ratio (e.g., 75 IU FSH + 75 IU LH per vial).

Mechanism of Action

HMG acts through two distinct G-protein-coupled receptors:

• FSH receptor on ovarian granulosa cells and testicular Sertoli cells
  • Drives follicular recruitment, estradiol production, and (in males) spermatogenesis support
• LH/hCG receptor on ovarian theca cells and testicular Leydig cells
  • Stimulates androgen synthesis (converted in granulosa cells to estradiol) and triggers ovulation at surge concentrations

The combined FSH/LH activity of HMG supports the "two-cell, two-gonadotropin" model of ovarian steroidogenesis, in which LH-stimulated androgen production in theca cells is aromatized to estradiol in FSH-stimulated granulosa cells. In males, LH drives testicular testosterone production and FSH supports Sertoli cell and spermatogenic function.

Research Summary

HMG has been used for decades as a gold-standard reference for gonadotropin efficacy.

Pharmacokinetics

HMG is administered subcutaneously or intramuscularly in research and clinical protocols. Following injection, FSH activity has a plasma half-life of approximately 24 hours, while the LH/hCG component exhibits a longer half-life of 12–48 hours depending on the relative hCG contribution.

Bioavailability via IM or SC routes is high, and steady-state FSH levels are typically reached after several days of daily injection. Clearance is primarily hepatic and renal, with deglycosylation and proteolysis producing fragments that are excreted in urine and bile.

Common Discussion Topics

• Comparison with highly purified urinary FSH and recombinant FSH/LH
• Role of urinary hCG contamination in LH activity measurement
• HMG vs rFSH in long-agonist vs antagonist IVF protocols
• Variability between manufacturing lots and sources
• Use in male fertility research alongside hCG

Related Compounds

• Gonadorelin — GnRH decapeptide used for upstream stimulation
• GnRH — endogenous hypothalamic decapeptide
• Buserelin — GnRH agonist used in fertility protocols
• Leuprolide — long-acting GnRH agonist
• Kisspeptin — upstream hypothalamic regulator of gonadotropin release

Educational information only. HMG is a prescription medicinal product. This article does not constitute medical advice or a recommendation for self-administration.