Usage
Human Menopausal Gonadotropin (hMG) is a purified preparation of gonadotropins extracted from the urine of postmenopausal women. It is prescribed for:
- Female infertility: Specifically, anovulatory infertility (including polycystic ovary syndrome) in women who haven’t responded to clomiphene citrate. It stimulates follicular development and maturation, inducing ovulation.
- Controlled ovarian hyperstimulation: Used in assisted reproductive technologies (ART) such as in-vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and intracytoplasmic sperm injection (ICSI). It promotes the development of multiple follicles.
- Male infertility: Specifically, hypogonadotropic hypogonadism. Stimulates spermatogenesis in males with insufficient follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Often used in conjunction with human chorionic gonadotropin (hCG).
Pharmacological Classification: Gonadotropin
Mechanism of Action: hMG acts like endogenous FSH and LH, binding to their respective receptors in the gonads. In females, FSH stimulates follicular growth and estradiol production, while LH triggers ovulation. In males, FSH stimulates Sertoli cells crucial for spermatogenesis, and LH stimulates Leydig cells to produce testosterone.
Alternate Names
- Generic: Menotropins
- Brand Names: Menopur, Repronex, Pergonal, Humegon
How It Works
Pharmacodynamics: hMG exerts its effect by mimicking the actions of endogenous gonadotropins, promoting gamete maturation and sex steroid production.
Pharmacokinetics:
- Absorption: Administered intramuscularly (IM) or subcutaneously (SC), hMG is absorbed systemically.
- Metabolism and Elimination: Primarily excreted via the kidneys. The pharmacokinetics in patients with hepatic or renal insufficiency isn’t well established.
Mode of Action:
- Receptor Binding: hMG binds to FSH and LH receptors on granulosa and theca cells in the ovaries (females) and Sertoli and Leydig cells in the testes (males).
- Enzyme Inhibition/Neurotransmitter Modulation: Not directly applicable to hMG’s primary mechanism.
Dosage
Standard Dosage
Adults:
- Anovulatory Infertility: 75-150 IU daily, initiated within the first 7 days of the menstrual cycle. Dose adjustments are based on ovarian response, typically no more frequently than every 7 days, in increments of 37.5 IU, not exceeding 75 IU. Maximum daily dose: 225 IU.
- Controlled Ovarian Hyperstimulation (ART): 150-225 IU daily, starting on day 2 or 3 of the cycle (GnRH antagonist protocol) or about 2 weeks after starting GnRH agonist therapy (GnRH agonist protocol). Dose adjustments are based on ovarian response, not exceeding 150 IU per adjustment. Maximum daily dose: 450 IU. Treatment typically doesn’t exceed 20 days.
- Male Infertility: 75-150 IU two to three times a week, often in combination with hCG. Treatment duration: 3-4 months or longer.
Children:
hMG isn’t typically used in children except in specific cases of prepubertal cryptorchidism under strict specialist supervision.
Special Cases:
- Elderly Patients: Not generally recommended.
- Renal Impairment: No established guidelines. Use with caution due to renal excretion.
- Hepatic Dysfunction: No established guidelines. Use with caution.
- Patients with Comorbid Conditions: Consider individual patient factors.
Clinical Use Cases The use cases mentioned are not applicable for hMG. hMG is used for infertility, not for situations like intubation or surgical procedures.
Dosage Adjustments
Adjustments are made based on individual responses, monitoring follicle development via ultrasound and estradiol levels. Adjustments are also necessary in cases of renal or hepatic impairment, though no specific guidelines are available.
Side Effects
Common Side Effects:
- Injection site reactions (pain, redness, swelling)
- Headache
- Abdominal discomfort/bloating
- Nausea
- Mood changes
- Fatigue
Rare but Serious Side Effects:
- Ovarian Hyperstimulation Syndrome (OHSS): Characterized by ovarian enlargement, fluid accumulation in the abdomen and chest, and potential complications like thromboembolism. Requires urgent medical attention.
- Multiple pregnancies
Long-Term Effects:
Limited data are available on long-term effects.
Adverse Drug Reactions (ADR):
OHSS is a serious ADR requiring immediate intervention.
Contraindications
- Hypersensitivity to hMG or any component
- Pregnancy
- Breastfeeding
- Tumors of the ovaries, uterus, breast, pituitary, hypothalamus, prostate, or testes
- Unexplained vaginal bleeding
- Ovarian cysts/enlargement (not due to PCOS)
- Primary ovarian failure
Drug Interactions
- Clomiphene citrate: May enhance follicular response.
- GnRH agonists/antagonists: May alter dosage requirements.
Pregnancy and Breastfeeding
- Pregnancy Category: X (contraindicated)
- Breastfeeding: Not recommended as excretion in breast milk is unknown.
Drug Profile Summary
- Mechanism of Action: Stimulates follicular development and maturation in females, spermatogenesis in males, by mimicking endogenous FSH and LH.
- Side Effects: Injection site reactions, headache, abdominal discomfort, nausea, mood changes, OHSS (rare but serious).
- Contraindications: Pregnancy, breastfeeding, reproductive cancers, pituitary/hypothalamic tumors.
- Drug Interactions: Clomiphene citrate, GnRH agonists/antagonists.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended while breastfeeding.
- Dosage: Variable, depending on indication and patient response.
- Monitoring Parameters: Follicle size (ultrasound), estradiol levels.
Popular Combinations
- hCG: Often used in conjunction with hMG for final follicular maturation before ovulation induction or to support spermatogenesis.
- GnRH agonists/antagonists: Used to prevent premature ovulation during controlled ovarian hyperstimulation.
Precautions
- Careful monitoring of ovarian response during treatment.
- Assess for risk factors for OHSS (e.g., PCOS).
- Screen for contraindications before initiation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Human Menopausal Gonadotrophin?
A: Dosage is individualized based on the indication and patient response. For anovulatory infertility, 75-150 IU daily is typical. For controlled ovarian hyperstimulation, 150-225 IU daily. For male infertility, 75-150 IU two to three times weekly.
Q2: What are the common side effects of hMG?
A: Common side effects include injection site reactions, headache, abdominal discomfort, bloating, nausea, mood swings, and fatigue.
Q3: What is Ovarian Hyperstimulation Syndrome (OHSS)?
A: OHSS is a rare but potentially serious complication characterized by ovarian enlargement, fluid accumulation, and possible thromboembolic events.
Q4: Can hMG be used during pregnancy?
A: No, hMG is contraindicated during pregnancy.
Q5: Is it safe to breastfeed while taking hMG?
A: hMG is not recommended during breastfeeding as its excretion in breast milk is unknown.
Q6: What are the contraindications for hMG use?
A: Contraindications include reproductive cancers, pituitary or hypothalamic tumors, unexplained vaginal bleeding, and primary ovarian failure.
Q7: How is hMG administered?
A: hMG is administered via intramuscular (IM) or subcutaneous (SC) injection.
Q8: How is the dosage of hMG adjusted?
A: Dosage adjustments are made based on individual patient response, as assessed by ultrasound monitoring of follicle development and serum estradiol levels.
Q9: How should hMG be used in patients with renal or hepatic impairment?
A: Use with caution in patients with renal or hepatic dysfunction due to lack of specific dosage guidelines. Close monitoring is essential.
