INDICATIONS FOR USE

Human Chorionic Gonadotropin (hCG) is used off-label in male hormone Human Chorionic Gonadotropin (hCG) is used off-label in male hormone replacement therapy to preserve testicular function and fertility. It is commonly used in men receiving exogenous testosterone to prevent or reverse testicular atrophy, maintain intratesticular testosterone production, and stimulate spermatogenesis. hCG may also be used as a primary treatment in men with secondary hypogonadism who wish to avoid testosterone therapy.

EVIDENCE RATING

✦✦ : Early but compelling human efficacy and safety data.

ROUTE OF ADMINISTRATION

• Subcutaneous or intramuscular injection

COMMON INITIAL DOSING REGIMENS

• A typical starting dose is 250-500iU (subcutaneously or intramuscular) 2-3 times weekly. 

• hCG can also be dosed daily for more even effects.

MECHANISM OF ACTION

• hCG is a glycoprotein hormone structurally similar to luteinizing hormone (LH). When administered, it acts as an LH analog, directly stimulating the Leydig cells in the testes to produce testosterone. In men on exogenous testosterone therapy, hCG helps maintain intratesticular testosterone concentrations, which are critical for preserving sperm production and testicular volume.

• Unlike GnRH analogs, hCG bypasses the hypothalamus and pituitary, acting directly on the testes. This makes it useful in situations where upstream hypothalamic or pituitary function is impaired or suppressed.

COMMON SIDE EFFECTS

• General: Fatigue, mood fluctuations, and mild bloating.

• Endocrine: Elevated estradiol levels due to increased aromatization of testosterone may lead to gynecomastia, fluid retention, or increased emotional sensitivity.

• Injection Site: Local irritation, redness, or swelling.

• Rare: Ovarian hyperstimulation syndrome (in women), thromboembolic events, or allergic reactions. In men, rare complications may include acne, increased libido, or headaches.

CONTRAINDICATIONS

• Absolute: Known hypersensitivity to hCG or any excipients in the formulation; known or suspected hormone-sensitive tumors (e.g., prostate cancer, breast cancer).

• Relative: Use with caution in individuals with cardiovascular disease, uncontrolled hypertension, or a history of clotting disorders, due to potential fluid retention and estradiol elevation.

COMPARISON WITH OTHER AGENTS

• Gonadorelin: Unlike hCG, which directly mimics LH, gonadorelin stimulates the entire HPG axis by prompting endogenous LH and FSH secretion. Gonadorelin may offer more physiological regulation but requires an intact hypothalamic-pituitary function.

• Clomiphene Citrate or Enclomiphene: These SERMs indirectly stimulate testosterone production by blocking estrogen’s feedback inhibition on the hypothalamus, increasing endogenous GnRH and downstream LH and FSH. hCG is more direct and often used when a faster or more potent effect on testosterone or spermatogenesis is desired.

LEARN MORE

• Evidence hound? Review our comprehensive listing of PubMed direct links to original research related to this medication.