HCG

What it is

Human chorionic gonadotropin (hCG) is a 237-amino-acid glycoprotein hormone naturally produced by the syncytiotrophoblast cells of the placenta during pregnancy. Its primary physiologic function is supporting the corpus luteum in early pregnancy to maintain progesterone production until the placenta takes over progesterone production around 10 weeks gestation.

hCG consists of two subunits — an alpha subunit shared with LH, FSH, and TSH, and a unique beta subunit that confers hCG-specific activity. The structural similarity to LH allows hCG to bind and activate the LH receptor with high affinity, producing LH-like effects on reproductive tissues.

hCG has been used pharmaceutically for over a century. Brand-name hCG products (such as Pregnyl, Novarel, and Ovidrel) are FDA-approved for several reproductive indications including induction of ovulation in fertility protocols, treatment of cryptorchidism in male children, and treatment of hypogonadism in men. The hormone is sourced from the urine of pregnant women (uHCG, e.g., Pregnyl) or produced through recombinant technology (rhCG, e.g., Ovidrel).

Important to address: hCG was historically marketed for weight loss in combination with very low calorie diets. This use is not evidence-based, has been formally rejected by the FDA, and is not something we offer at The Tide.

Mechanism of action

hCG acts primarily through LH receptor activation:

• Testicular LH receptor activation in men: stimulates Leydig cells to produce testosterone, supports Sertoli cell function and spermatogenesis through the testicular hormonal milieu, and maintains testicular size.
• Ovarian effects in women: in fertility contexts, hCG triggers ovulation by mimicking the natural LH surge that initiates follicle rupture. In early pregnancy, hCG supports corpus luteum function.
• Long half-life: approximately 24 hours, substantially longer than native LH (about 20 minutes).
• Direct gonadal action: unlike gonadorelin (which acts upstream at the pituitary), hCG acts directly at gonadal receptors. Use of hCG in men receiving testosterone replacement therapy is off-label.

Research findings

hCG has substantial clinical evidence across its established indications:

Male hypogonadism: long-established use for stimulating endogenous testosterone production in select hypogonadism scenarios, particularly in men who want to maintain fertility.

Cryptorchidism: historical use in pediatric undescended testis treatment, though current pediatric urology often favors surgical approaches.

Female fertility: standard component of IVF and other assisted reproduction protocols for triggering ovulation. The “hCG trigger” is among the most established interventions in reproductive medicine.

Use during TRT (off-label): hCG is sometimes used in men receiving testosterone replacement therapy. This use is off-label and is not an FDA-approved indication; published evidence comes mainly from observational and small controlled studies.

Weight loss “HCG diet”: the proposed use of low-dose hCG with severe caloric restriction has been formally evaluated and shown to be ineffective beyond placebo. The FDA has issued warnings against this use. We do not offer HCG for weight loss.

Side effects and contraindications

Possible side effects:

• Estrogen conversion: hCG-driven testosterone production can drive aromatization to estradiol
• Gynecomastia: can develop secondary to estrogen elevation
• Water retention: mild fluid retention in some patients
• Mood changes: some men report mood effects; typically modest
• Injection site reactions
• Headache, fatigue: in some patients

Contraindicated in:

• Hormone-sensitive cancers, particularly prostate cancer in men and breast cancer
• Premature puberty in pediatric patients
• Active thrombophlebitis (rare concerns about thrombotic risk with hormonal manipulation)
• Pregnancy outside specific obstetric/reproductive contexts
• Known hypersensitivity to hCG

What we don’t yet know

Use of hCG in men receiving testosterone replacement therapy is off-label, and its long-term effects in that setting have not been established in large randomized trials. Long-term comparative outcomes between hCG-supported TRT and TRT alone (in terms of testicular function recovery if TRT is discontinued) would benefit from more formal study. hCG is FDA-approved for specific reproductive and endocrine indications; it is not effective for weight loss, including the “HCG diet” applications we do not offer.