NOT FOR HUMAN CONSUMPTION

HMG (menotropins) is a urinary-derived gonadotropin mixture containing both FSH and LH activity (classically 75 IU FSH + 75 IU LH per vial in many products). It’s used for ovulation induction and for controlled ovarian stimulation in ART/IVF protocols.

Core concept
FSH primarily drives follicle recruitment and growth, while LH activity supports steroidogenesis and follicular maturation—useful in selected patients (e.g., certain “low LH” contexts) and in ART stimulation strategies.

Regulatory status
Menotropins are approved medicines in many regions (e.g., MENOPUR is widely licensed), but indications and labeling vary by country/product.

Additional Benefits / Clinical Effects Often Discussed (and what evidence actually shows)

Evidence quality note: HMG is “older but established.” The big question in modern literature is usually comparative effectiveness vs rFSH (and in which subgroups/protocols), rather than “does it work at all.”

2) Molecular Mechanism of Action

2.1 Receptor pharmacodynamics

• FSHR (granulosa cells): ↑ follicle recruitment/growth, ↑ aromatase activity → ↑ estradiol, supports oocyte maturation environment.

• LHR (theca/granulosa in later stages): ↑ androgen substrate production (theca), supports late follicular maturation and luteinization steps (timing depends on protocol).
  HMG delivers both activities via menotropins preparations.

2.2 Down-stream biology (high-level map)

3) Pharmacokinetics (PK) (practical framing)

• Route: typically subcutaneous (some products also allow IM).

• PK varies by product/purification (HMG is a biologic mixture). Labels focus more on clinical monitoring (ultrasound + estradiol) than a single “set-and-forget” PK target.

4) Clinical Evidence (what’s most cited)

4.1 ART/IVF stimulation

• RCTs and meta-analyses compare HMG vs rFSH with varied protocols. Some systematic reviews conclude insufficient evidence of a difference in ongoing pregnancy/live birth overall; other analyses report higher clinical pregnancy in certain long GnRH-agonist down-regulation settings.

4.2 Anovulatory infertility / ovulation induction

• Used under specialist supervision for inducing ovulation in selected patients, with careful monitoring to reduce OHSS and multiple gestation risk.

5) Emerging clinical interests (where clinicians debate “why HMG?”)

6) Safety and tolerability (label-level essentials)

Major risks (class-defining):

• OHSS (Ovarian Hyperstimulation Syndrome): can be serious; requires ultrasound/estradiol monitoring; withhold hCG trigger if ovaries are overly enlarged to reduce OHSS risk (per labeling).

• Multiple pregnancy risk is increased with gonadotropin stimulation.

• Thromboembolic events / serious pulmonary complications: reported (rare but important).

• Ovarian torsion: reported after gonadotropin treatment.

Contraindications are product-specific, but commonly include: primary ovarian failure (high baseline FSH), certain ovarian cysts not due to PCOS, hormone-dependent tumors, uncontrolled thyroid/adrenal disorders, and pregnancy (varies by label).

Comparative “matrix” (conceptual)

7) Regulatory / supply notes (practical)

• Menopur has had quality-defect–related supply communications in Europe (example: EMA DHPC notice), reminding that sourcing and batch quality can matter with biologics.

8) Future directions (what would sharpen decision-making)

• Better subgroup identification (who truly benefits from built-in LH activity vs FSH-only).

• Head-to-head trials using live birth as primary endpoint with modern protocols and standardized dosing rules (a recurring recommendation in reviews).

Selected references

• MENOPUR FDA label / description and composition:

• UK SmPC (composition/indications):

• Comparative effectiveness reviews/meta-analyses (HMG vs rFSH):

• EMA DHPC (supply/quality communication example):