Menotropin Injection (Human Menopausal Gonadotropin / hMG)

What Is It?

Menotropin, also called human menopausal gonadotropin (hMG), is a purified urinary extract of FSH and LH obtained from the urine of postmenopausal women. It contains both FSH and LH in equal bioactivity (75 IU FSH : 75 IU LH per vial). The current commercial preparation (e.g., Menopur, Ferring Pharmaceuticals) is highly purified, with hCG added to maintain the 1:1 FSH:LH ratio. — Katzung's Basic and Clinical Pharmacology, 16th Ed.

Mechanism of Action

Menotropin acts through G protein-coupled receptors for FSH and LH on gonadal tissue:

In Women

FSH component: Stimulates ovarian follicle growth and granulosa cell conversion of androgens → estrogens
LH component: Stimulates theca cell androgen production and, in the luteal phase, progesterone and estrogen synthesis
Together, FSH + LH drive folliculogenesis, ovarian steroidogenesis, and ultimately ovulation

In Men

FSH: Primary regulator of spermatogenesis; stimulates Sertoli cells to produce androgen-binding protein and convert testosterone → estrogen (needed for sperm development)
LH: Stimulates Leydig cells to synthesize testosterone, maintaining high local androgen concentrations near developing sperm

Pharmacokinetics

Feature	Detail
Source	Postmenopausal urine (highly purified)
Route	Subcutaneous (SC) or intramuscular (IM) injection
Dosing frequency	Usually daily
Half-life	10–40 hours (varies by route and preparation)
Content per vial	75 IU FSH + 75 IU LH activity

Clinical Indications

1. Female Infertility — Ovulation Induction

Used for anovulation due to:

Hypogonadotropic hypogonadism
Polycystic ovary syndrome (PCOS) (when clomiphene fails)
Other causes of secondary anovulation

2. Controlled Ovarian Stimulation (COS)

The cornerstone of assisted reproductive technologies (ART) including:

In vitro fertilization (IVF)
Intrauterine insemination (IUI) — raises delivery rate from ~8% with clomiphene to 15–18%

Typical COS protocol:

Daily injections begin ~day 2 of the menstrual cycle
Follicle growth monitored by ultrasound
Once follicles mature: hCG (3,300–10,000 IU SC) triggers final oocyte maturation
A GnRH agonist or antagonist co-administered to prevent premature LH surge
Luteal phase supported with progesterone (preferred over hCG to reduce OHSS risk)

3. Male Infertility (Hypogonadotropic Hypogonadism)

Initial treatment: hCG alone (1,500 IU IM 3× weekly) for 8–12 weeks to raise testosterone
If spermatogenesis still insufficient: hMG added at 75–150 IU 3× per week
Takes 4–6 months for sperm to appear in ejaculate in up to 90% of patients
May take 18–24 months for full restoration of spermatogenesis

Adverse Effects

Serious

Complication	Details
Ovarian Hyperstimulation Syndrome (OHSS)	Ovarian enlargement, hypovolemia, ascites, liver dysfunction, pulmonary edema, electrolyte imbalance, thromboembolic events; can require ICU admission
Multiple Pregnancy	Risk ~5–10% with ovulation induction (vs ~1% general population); carries risks of gestational diabetes, preeclampsia, preterm labor

Other

Headache, depression, edema
Precocious puberty (in children)
Gynecomastia in men (directly related to testosterone levels during treatment)
Rarely: antibodies to hCG

Contraindications

(From Berek & Novak's Gynecology — Absolute/Relative Contraindications)

Primary ovarian failure with elevated FSH
Uncontrolled thyroid or adrenal dysfunction
Organic intracranial lesion (e.g., pituitary tumor)
Undiagnosed abnormal uterine bleeding
Ovarian cysts or enlargement not due to PCOS
Prior hypersensitivity to the gonadotropin
Sex hormone-dependent tumors of the reproductive tract
Pregnancy

Available Preparations

Trade Name	Compound	Source	FSH	LH Activity	Route
Menopur (Ferring)	Menotropin + urinary hCG	Highly purified urinary	75 IU	75 IU	SC
Gonal-F (EMD Serono)	Follitropin alfa	Recombinant FSH	75 IU	None	SC
Follistim (Merck)	Follitropin beta	Recombinant FSH	75 IU	None	SC

Menotropin is the only product providing both FSH and LH activity in a single injection, making it distinct from the recombinant FSH-only preparations.

Key Clinical Notes

Gonadotropins are second-line for female infertility — reserved after failure of simpler agents (e.g., clomiphene)
Requires close monitoring (serial ultrasound, estradiol levels) due to OHSS risk
In men: testicular volume >8 mL and postpubertal onset of hypogonadism predict better response
Prior testosterone therapy does not preclude response to subsequent gonadotropin therapy

Sources: Katzung's Basic and Clinical Pharmacology 16e | Harrison's Principles of Internal Medicine 22e | Berek & Novak's Gynecology

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