hMG

Overview

hMG (Human Menopausal Gonadotropin) is a hormonal preparation extracted from the urine of post-menopausal women. It contains a combination of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) in approximately equal amounts (typically 75 IU of each per vial).

It has been a cornerstone of fertility medicine since its introduction in the 1960s and remains widely used for both female ovulation induction and male fertility optimization.

Key Characteristics

• Origin: Extracted from post-menopausal urine
• Classification: Gonadotropin preparation
• Composition: FSH + LH (approximately 1:1 ratio)
• Primary Use: Fertility treatments, hormonal optimization
• FDA Status: Approved for fertility indications

Mechanism

hMG works by directly stimulating the gonads, bypassing the hypothalamic-pituitary axis.

Primary Mechanisms

1. FSH Actions

Follicle Stimulating Hormone acts on:

In Women:

• Stimulates ovarian follicle development
• Promotes estrogen production from granulosa cells
• Induces aromatase enzyme activity
• Essential for egg maturation

In Men:

• Stimulates Sertoli cells in the testes
• Promotes spermatogenesis
• Supports sperm maturation
• Maintains testicular function during HRT

2. LH Actions

Luteinizing Hormone provides:

In Women:

• Triggers ovulation at mid-cycle (natural surge)
• Promotes corpus luteum formation
• Stimulates progesterone production
• Essential for maintaining early pregnancy

In Men:

• Stimulates Leydig cells
• Promotes testosterone production
• Supports testicular volume maintenance
• Works synergistically with FSH

3. Synergistic Effect

The combination of FSH and LH in hMG provides a more "natural" stimulation pattern than FSH-only preparations, particularly important for:

• LH-deficient patients
• Male fertility optimization
• Cases where pure FSH has failed

Research

Female Fertility

Ovulation Induction

Well-established uses include:

• Polycystic Ovary Syndrome (PCOS) treatment
• Hypothalamic amenorrhea
• WHO Group II anovulation
• Controlled ovarian hyperstimulation for IVF

2025 Developments

Recent protocols focus on:

• Individualized dosing based on AMH and AFC
• Reduced hyperstimulation risk with careful monitoring
• Combination with GnRH antagonists for cycle control

Male Fertility

Spermatogenesis Induction

hMG is particularly valuable for:

• Hypogonadotropic hypogonadism
• Post-anabolic steroid fertility restoration
• Testicular atrophy reversal
• Maintaining fertility during TRT

Clinical Outcomes

Studies show:

• 50-80% success rate in achieving adequate sperm counts
• Typically requires 6-12 months of treatment
• Superior to FSH-only in many cases
• Better testicular volume preservation

Comparison Studies

Research comparing hMG to recombinant FSH shows:

• Similar pregnancy rates in IVF
• hMG may provide better outcomes in poor responders
• LH component beneficial in certain patient populations
• Cost-effectiveness often favors hMG

Dosing

Research Protocols

Administration Notes

For Fertility Protocols

• Begin on day 2-3 of menstrual cycle (women)
• Requires ultrasound monitoring for follicle development
• Adjust dose based on estradiol levels and follicle count
• Typically combined with hCG trigger for ovulation

For Male Use

• Usually combined with hCG (1000-2000 IU 2-3x weekly)
• hCG provides LH-like stimulation for testosterone
• hMG provides additional FSH for spermatogenesis
• Monitor sperm count every 2-3 months

Reconstitution

• Comes as lyophilized powder with diluent
• Mix gently - do not shake
• Use immediately after reconstitution
• Store unreconstituted vials refrigerated

Pharmacokinetics

Absorption

• Subcutaneous: Peak levels in 12-24 hours
• Intramuscular: Similar absorption profile
• Bioavailability approximately 70%

Distribution

• FSH half-life: 24-48 hours
• LH half-life: 20-24 hours
• Accumulation occurs with daily dosing

Metabolism

• Primarily hepatic metabolism
• Both hormones cleared by liver and kidneys

Elimination

• FSH: Slower clearance, more stable levels
• LH: Faster clearance, more pulsatile activity
• Terminal half-life allows every-other-day dosing

Comparison: hMG vs Other Gonadotropins

| Feature | hMG | Recombinant FSH | hCG | |---------|-----|-----------------|-----| | Contains FSH | Yes | Yes | No | | Contains LH | Yes | No | LH-like activity | | Origin | Urinary | Recombinant | Urinary/Recombinant | | Primary Use | Fertility | Ovulation | Trigger/Testosterone | | Cost | Moderate | Higher | Lower | | LH-Deficient Patients | Preferred | May need LH added | Not sufficient |

Synergy & Stacking

Common Combinations

hMG + hCG (Male Fertility)

The standard combination for male fertility:

• hCG 1000-2000 IU 2-3x weekly (for testosterone)
• hMG 75-150 IU 2-3x weekly (for spermatogenesis)
• Duration: 6-12 months minimum
• Monitor testosterone and sperm parameters

hMG + GnRH Antagonist (Female IVF)

For controlled ovarian stimulation:

• hMG provides follicular stimulation
• Antagonist prevents premature LH surge
• Allows precise timing of egg retrieval

hMG + Clomiphene (Conservative Protocol)

For mild stimulation:

• Clomiphene first, then low-dose hMG
• Reduces medication costs
• Lower risk of hyperstimulation

Safety

Known Side Effects

Common (Women)

• Ovarian hyperstimulation syndrome (OHSS) - dose-related
• Bloating and abdominal discomfort
• Mood changes
• Headache
• Injection site reactions

Common (Men)

• Gynecomastia (due to increased estrogen)
• Acne
• Injection site reactions
• Testicular tenderness

Serious Risks

• Multiple pregnancy (with ovulation induction)
• Severe OHSS requiring hospitalization
• Thromboembolic events (rare)
• Ectopic pregnancy

Contraindications

Absolute Contraindications:

• Primary ovarian/testicular failure
• Uncontrolled thyroid or adrenal dysfunction
• Sex hormone-dependent tumors
• Pregnancy
• Unexplained vaginal bleeding

Relative Contraindications:

• High baseline estradiol
• Large ovarian cysts
• Severe obesity
• Previous severe OHSS

Monitoring

For Women (Fertility Treatment)

During Stimulation:

• Transvaginal ultrasound every 2-3 days
• Serum estradiol levels
• Follicle count and size measurement
• Endometrial thickness

Safety Monitoring:

• Watch for OHSS symptoms
• Multiple follicle development
• Ovarian enlargement

For Men

Baseline:

• Semen analysis
• Testosterone, FSH, LH levels
• Testicular ultrasound

During Treatment:

• Semen analysis every 2-3 months
• Hormone levels periodically
• Estradiol (watch for elevation)

Regulatory

Current Status

| Region | Status | |--------|--------| | United States | FDA-approved (Menopur, Repronex) | | European Union | EMA-approved | | WADA | Not banned | | Availability | Prescription only |

Legal Considerations

• Legally available by prescription worldwide
• Covered by insurance for fertility indications
• Off-label use for male optimization common
• Requires medical supervision and monitoring

Clinical Outlook

hMG remains a valuable option in fertility medicine, particularly for:

• Patients with LH deficiency
• Male fertility optimization
• Cost-conscious treatment approaches
• Cases where recombinant FSH alone fails

References