HUMAN CHORIONIC GONADOTROPIN (HCG)

Mechanism of Action
Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced during pregnancy by the placental trophoblast. Structurally and functionally, it is very similar to pituitary luteinizing hormone (LH): both share the same alpha subunit and differ slightly in the beta subunit, which allows hCG to bind to and activate the LH/CG receptor. When administered, hCG mimics the action of endogenous LH. In women, it stimulates ovulation and progesterone production by the corpus luteum; in men, it acts on Leydig cells in the testes to increase testosterone synthesis. hCG has a longer half-life than LH (≈24–36 hours vs. ~20 minutes for LH), which provides a more sustained stimulatory effect on the gonads. As a result, an hCG injection can trigger final ovarian follicle maturation (analogous to the natural “LH surge”) or restore intratesticular testosterone production in cases of hypogonadotropic hypogonadism. In summary, hCG “replaces” the LH signal in the body, maintaining gonadal function (steroidogenesis and gametogenesis) when endogenous LH is deficient or suppressed.
 
Clinical or Therapeutic Uses
hCG is widely used in reproductive medicine. In women, it is administered in fertility treatments to induce ovulation in assisted reproduction protocols: a dose of hCG simulates the natural LH surge and triggers release of the mature oocyte. It is also used after ovulation to support the luteal phase, sustaining progesterone production necessary for implantation. In men, hCG is a cornerstone therapy for hypogonadotropic hypogonadism (e.g., pituitary gonadotropin deficiency): periodic administration stimulates testosterone production and can reactivate spermatogenesis, improving male fertility. It is commonly used in spermatogenesis induction protocols and in men with infertility secondary to anabolic steroid use, with favorable outcomes in sperm count recovery. In pediatrics, hCG is part of the management of cryptorchidism (undescended testicle), where it is given to promote testicular descent by stimulating local androgen production. Outside reproductive medicine, hCG gained popularity in weight-loss regimens (the “hCG diet”), but clinical trials have shown that any weight loss is due solely to severe caloric restriction, not the hormone itself; thus, its use for weight loss is considered ineffective and potentially risky. In sports doping, hCG has been used primarily by male athletes. Because exogenous anabolic steroids suppress the hypothalamic–pituitary–gonadal axis (inhibiting endogenous LH), some bodybuilders administer hCG during or after steroid cycles to “reactivate” the testes and maintain testosterone production. This helps prevent testicular atrophy and abrupt testosterone drops when steroids are discontinued, facilitating hormonal recovery (post-cycle therapy). Due to this use, the World Anti-Doping Agency prohibits hCG in male competitors (but not in women). In women, hCG does not enhance athletic performance, and elevated levels may indicate pregnancy; therefore, it is considered doping only in men.
 
Side Effects or Associated Risks
hCG treatment is relatively safe at physiological doses, but in fertility settings or with misuse it can carry significant adverse effects. In women, the main concern is ovarian hyperstimulation syndrome (OHSS) when gonadotropins and hCG are used to induce ovulation. OHSS results from an exaggerated ovarian response: the ovaries enlarge and release mediators that cause fluid accumulation in the abdomen and chest. Symptoms include severe pelvic pain, abdominal distension, nausea, vomiting, and rapid weight gain; in severe cases, thrombosis or renal failure may occur. Although uncommon, it is a serious complication requiring medical attention. In men, the sudden increase in testosterone induced by hCG can lead to excessive conversion to estrogens (aromatization), resulting in gynecomastia (male breast tissue growth). Acne, oily skin, and fluid retention may also occur, resembling pubertal effects due to hormonal elevation. In both men and women, hormonal fluctuations can cause mood changes (irritability, mood swings). Other reported effects include headache, fatigue, and injection-site reactions. In prepubertal girls, exposure to exogenous hCG could trigger premature secondary sexual characteristics (e.g., body hair, voice deepening, early menstruation), so its use in pediatrics must be carefully controlled. A transient increase in testicular size may occur in young males due to intense gonadal stimulation. Additionally, there is a low but documented risk of thromboembolic events associated with hCG use, partly related to the hypercoagulable state that can accompany OHSS. As a safety measure, hormone-sensitive tumors (e.g., prostate cancer) should be ruled out before initiating hCG therapy, as increased testosterone could exacerbate such conditions. In summary, although hCG is well tolerated in most patients, its use should be medically supervised—especially in fertility treatments—to promptly manage any complications.