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. It is 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). This allows infrequent (typically 2–3 times weekly) dosing for chronic use.
• Direct gonadal action: unlike gonadorelin (which acts upstream at the pituitary), hCG acts directly at gonadal receptors. This means hCG works even when the pituitary is suppressed (e.g., during testosterone replacement therapy), making it valuable for maintaining gonadal function during TRT.

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.

Maintenance of testicular function during TRT: well-established practitioner experience supports the use of hCG to maintain testicular size, spermatogenesis, and fertility in men on testosterone replacement therapy. Clinical evidence comes from extensive observational use and smaller controlled studies.

Recovery from anabolic steroid use: hCG is sometimes used in protocols to recover endogenous testosterone production after suppression from anabolic steroid use.

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.

How we use it at The Tide

Our primary uses of hCG:

• Maintenance of testicular function during TRT: the most common use. Men on testosterone replacement therapy who want to preserve testicular size, function, and fertility receive periodic hCG injections to provide exogenous LH-like stimulation.
• Selected male infertility workups: in coordination with reproductive medicine specialists when appropriate.
• HPG axis recovery support: for men discontinuing TRT who want to support recovery of endogenous testosterone production.

Standard dosing for TRT support: 250–500 IU subcutaneously, 2–3 times weekly. Some patients require higher doses; we titrate based on testicular size, testosterone levels (recognizing that hCG itself elevates testosterone), and patient experience.

Monitoring: testicular size assessment, testosterone, estradiol (hCG can drive estradiol conversion in some men), hematocrit, and other standard TRT monitoring parameters.

Side effects and contraindications

hCG is generally well-tolerated:

• Estrogen conversion: hCG-driven testosterone production can drive aromatization to estradiol, sometimes requiring dose adjustment or aromatase inhibitor management
• Gynecomastia: can develop secondary to estrogen elevation; typically reversible with dose adjustment
• 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

Optimal dosing patterns for testicular preservation during TRT — frequency, dose magnitude, individualized targeting — are based largely on practitioner experience rather than 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. The optimal balance between hCG, gonadorelin, and other approaches to maintaining HPG function during TRT is largely individualized rather than protocol-driven. Supply chain issues with hCG have made consistent prescribing challenging at times, driving increased use of gonadorelin as an alternative — the long-term implications of this practice shift are still being characterized. We present hCG honestly: an established peptide hormone with decades of clinical use for legitimate reproductive and endocrine indications, with clear distinction between evidence-based uses and the ineffective “HCG diet” applications we do not offer.