HormonalWell-Tolerated

hCG

Also known as: Human Chorionic Gonadotropin, Pregnyl, Novarel, Ovidrel

Human Chorionic Gonadotropin, a hormone that mimics LH to stimulate testosterone production. Commonly used for fertility, TRT support, and post-cycle therapy.

Half-Life

24-36 hours

Typical Dose

250-500 IU

Frequency

2-3x weekly

Routes

Subcutaneous

Overview

Human Chorionic Gonadotropin (hCG) is a naturally occurring hormone produced during pregnancy. In males, hCG mimics Luteinizing Hormone (LH), stimulating the Leydig cells in the testes to produce testosterone. This makes it invaluable for maintaining testicular function during testosterone replacement therapy (TRT) and for fertility preservation.

hCG has been FDA-approved for decades for both fertility treatment and certain hormonal conditions, making it one of the most well-established peptide hormones in clinical use.

Key Characteristics

  • Origin: Natural hormone (pregnancy), also produced via recombinant technology
  • Classification: Gonadotropin hormone
  • FDA Status: Approved for fertility and specific hormonal conditions
  • Unique Feature: Directly stimulates endogenous testosterone production
  • Primary Use: TRT support, fertility, post-cycle therapy

Why hCG Matters for TRT

When on TRT, the body's natural LH production shuts down. Without LH:

  • Testes shrink (testicular atrophy)
  • Natural testosterone production ceases
  • Fertility is impaired
  • Pregnenolone/DHEA production decreases

hCG prevents these issues by acting as an LH substitute.

Mechanism

Primary Mechanisms

1. LH Receptor Activation

hCG's primary action:

  • Binds to LH/hCG receptors on Leydig cells
  • Activates cAMP signaling cascade
  • Stimulates testosterone synthesis
  • Maintains intratesticular testosterone (ITT)

2. Testicular Preservation

During TRT:

  • Prevents testicular atrophy
  • Maintains sperm production
  • Preserves fertility potential
  • Supports testicular health

3. Upstream Hormone Support

Beyond testosterone:

  • Maintains pregnenolone production
  • Supports DHEA synthesis
  • Preserves neurosteroid production
  • May improve well-being

4. Ovarian Stimulation (Women)

In females:

  • Triggers ovulation
  • Used in fertility treatments
  • Supports corpus luteum
  • Maintains early pregnancy

Research

Research Note: hCG has extensive clinical research and decades of FDA-approved use. It is one of the most well-studied hormones in medicine.

TRT Combination Studies

Testicular Function Preservation

Research demonstrates:

  • Maintains testicular volume during TRT
  • Preserves sperm production in most men
  • Intratesticular testosterone remains adequate
  • Prevents the "shutdown" associated with TRT alone

Fertility Research

Male Fertility

Studies show:

  • Can restore spermatogenesis during/after TRT
  • Effective for hypogonadotropic hypogonadism
  • Works synergistically with FSH (hMG)
  • Higher success rates when started early

Female Fertility

Well-established for:

  • Ovulation induction
  • IVF trigger shots
  • Luteal phase support
  • Polycystic ovary syndrome

Post-Cycle Therapy

Steroid Discontinuation

Research indicates:

  • Accelerates testosterone recovery
  • Reduces hypogonadal symptoms
  • May shorten recovery time
  • Best combined with SERMs

Dosing

Disclaimer: hCG is a prescription medication. Dosing should be determined by a healthcare provider based on individual needs and lab work.

Research Protocols

ProtocolDoseFrequencyDuration
TRT Support250-500 IU2-3x weeklyOngoing with TRT
Fertility Preservation500-1000 IU2-3x weeklyOngoing
Monotherapy1000-2000 IU2-3x weeklyAs prescribed
PCT500-1000 IUEvery other day2-4 weeks

Administration Notes

Timing

  • Can be taken any time of day
  • Consistent timing preferred
  • Often administered on non-TRT injection days
  • Some prefer same-day as TRT

Injection Technique

  • Subcutaneous preferred (less painful)
  • Intramuscular also effective
  • Rotate injection sites
  • Insulin syringes work well for SubQ

Reconstitution

  • Use bacteriostatic water
  • Typical: 5000 IU vial + 5ml water = 1000 IU/ml
  • Refrigerate after reconstitution
  • Use within 30-60 days

Finding the Right Dose

Signs of adequate dose:

  • Maintained testicular size
  • Preserved fertility (if desired)
  • Good energy and libido
  • Estrogen not excessively elevated

Signs dose may need adjustment:

  • Testicular shrinkage
  • Elevated estrogen symptoms
  • Fatigue or mood changes
  • Lab work indicating issues

Pharmacokinetics

Absorption

  • Subcutaneous: Slow, sustained absorption
  • Intramuscular: Moderate absorption
  • Peak levels: 6-24 hours post-injection

Distribution

  • Distributes to reproductive tissues
  • Crosses into testes
  • Limited CNS penetration

Metabolism

  • Primarily hepatic metabolism
  • Some renal clearance
  • Metabolites inactive

Elimination

  • Half-life: 24-36 hours
  • Allows 2-3x weekly dosing
  • No significant accumulation
  • Steady state: ~1 week

Synergy & Stacking

Common Combinations

hCG + TRT

Standard protocol:

  • TRT provides exogenous testosterone
  • hCG maintains testicular function
  • Prevents atrophy and fertility loss
  • Most common combination

hCG + hMG (or FSH)

For fertility:

  • hCG provides LH activity (testosterone)
  • hMG/FSH provides FSH activity (sperm)
  • Synergistic for spermatogenesis
  • Used when hCG alone insufficient

hCG + AI (Aromatase Inhibitor)

If estrogen elevated:

  • hCG can raise estrogen
  • Low-dose AI may be needed
  • Monitor estrogen levels
  • Adjust based on symptoms/labs

Timing Considerations

  • Can inject same day as TRT or alternate days
  • Some protocols spread doses throughout week
  • Consistency more important than specific timing
  • Individualize based on response

Safety

Known Side Effects

Common (dose-dependent)

  • Elevated estrogen (gynecomastia risk)
  • Water retention
  • Mood changes
  • Acne

Less Common

  • Headache
  • Irritability
  • Injection site reactions
  • Fatigue

With Excessive Use

  • Desensitization of Leydig cells (rare)
  • Persistent estrogen elevation
  • Testicular desensitization

Contraindications

Avoid if:

  • Prostate cancer
  • Hormone-sensitive cancers
  • Precocious puberty (in boys)
  • Hypersensitivity to hCG

Use with caution if:

  • History of blood clots
  • Heart disease
  • Migraine disorders
  • Asthma

Estrogen Management: hCG can significantly raise estrogen levels. Monitor for symptoms of elevated estrogen and check labs regularly. Some men may need an aromatase inhibitor.

Drug Interactions

  • May interact with other hormonal therapies
  • Can affect thyroid function tests
  • Coordinate with prescribing physician
  • Monitor when combining with other fertility drugs

Monitoring

Baseline Assessments

  • Total and free testosterone
  • Estradiol (E2)
  • LH and FSH
  • Complete blood count
  • Prostate-specific antigen (if indicated)

During Treatment

  • Testosterone levels (4-6 weeks after starting)
  • Estradiol monitoring
  • Testicular size assessment
  • Semen analysis (if fertility important)

Signs of Response

  • Stable testicular size
  • Testosterone levels appropriate
  • Estrogen not excessively elevated
  • Maintained fertility markers

Regulatory

Current Status

| Region | Status | |--------|--------| | United States | FDA-approved prescription medication | | WADA | Strictly Prohibited (S2 category) | | Availability | Prescription required; brand and generic available | | Insurance | Often covered for approved indications |

Legal Considerations

  • Schedule III in some jurisdictions
  • Requires prescription in most countries
  • Athletes: Strictly banned
  • Legitimate medical uses are protected

Clinical Outlook

hCG remains the gold standard for:

  • Testicular function preservation on TRT
  • Male fertility preservation
  • Ovulation induction in women
  • Hypogonadotropic hypogonadism treatment

Its long safety record and FDA approval make it a cornerstone of hormone optimization protocols.

References

[1] Coviello AD, et al.. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. Journal of Clinical Endocrinology & Metabolism (2005)
[2] Lee JA, Ramasamy R. Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men. Translational Andrology and Urology (2018)
[3] Kohn TP, et al.. The Effect of Subcutaneous Human Chorionic Gonadotropin on Testosterone Levels and Fertility Parameters. Fertility and Sterility (2019)
[4] Hormone Optimization Review. hCG in Testosterone Replacement Therapy: Protocols and Outcomes. Journal of Men's Health (2025)