hCG (human chorionic gonadotropin)

hCG is the only LH-mimetic in clinical use and one of a small number of peptide hormones with established FDA-approved indications. The branded preparations — Pregnyl, Novarel, Profasi (urinary-derived), and Ovidrel/choriogonadotropin alfa (recombinant) — are approved for prepubertal cryptorchidism, hypogonadotropic hypogonadism in men, and ovulation induction in women undergoing fertility treatment. The biohacker use case that dominates the modern conversation around hCG sits entirely off-label: TRT-adjunct, post-TRT recovery, and fertility-preserving monotherapy for secondary hypogonadism. The off-label uses are pharmacologically continuous with the approved indication for male hypogonadism, but the trial scaffolding underneath them is smaller and less recent than what supports, for example, tesamorelin in HIV-associated lipodystrophy.

Fertility-preserving adjunct to TRT. This is the load-bearing biohacker application. Exogenous testosterone suppresses pituitary LH and FSH output, intratesticular testosterone (normally ~100-fold higher than serum) collapses, and spermatogenesis arrests. Co-administering hCG maintains the LH signal at the Leydig cell, preserves intratesticular testosterone, and supports ongoing spermatogenesis through the duration of TRT. The dose-response evidence is anchored in Coviello et al., J Clin Endocrinol Metab 2005, 90:2595–2602, which randomized 29 men receiving testosterone enanthate 200 mg weekly to one of three hCG doses (125, 250, or 500 IU every other day) or placebo. Intratesticular testosterone — measured directly by testicular aspiration — increased linearly with hCG dose, and the 500 IU arm produced intratesticular testosterone roughly 26% above baseline despite full gonadotropin suppression from the testosterone arm. The clinical-endpoint companion is Hsieh et al., J Urol 2013, 189:647–650 — 26 hypogonadal men on testosterone supplemented with hCG 500 IU intramuscular every other day, none became azoospermic over a mean 6.2-month follow-up, and nine of 26 contributed to pregnancy during the observation window. The Coviello dose anchor and the Hsieh outcome anchor are the two papers that effectively defined modern TRT-plus-hCG protocols.

Post-TRT recovery. When exogenous testosterone is discontinued, the HPG axis must restart from a chronically suppressed state — sometimes over months, occasionally not at all. hCG is widely used as a component of restart protocols on the rationale that direct LHCGR stimulation maintains Leydig-cell capacity during the recovery window while pituitary function returns. The TRT discontinuation playbook covers the protocol architecture in more detail. The published evidence specifically for hCG in restart is thinner than for the fertility-preservation use case; the strongest signal comes from the broader male-infertility literature where hCG (alone or with FSH) reliably restores spermatogenesis in hypogonadotropic men over 6–24 months. The Rainer 2022 retrospective (Rainer et al., Cureus 2022, 14:e25826; n=28 men transitioning from exogenous testosterone to hCG monotherapy) reported that hCG-only therapy maintained testosterone levels, produced a small but statistically significant hematocrit decrease, and was free of thromboembolic or major cardiovascular events during the follow-up window — a useful safety signal in the specific population at issue, though limited by retrospective design and small sample.

Monotherapy for secondary hypogonadism. When the hypogonadism is hypothalamic-pituitary rather than testicular, direct LHCGR stimulation can restore testosterone without exogenous androgen. Habous et al., BJU Int 2018, 122:889–897 randomized 282 fertility-preserving hypogonadal men to clomiphene 50 mg daily, hCG 5,000 IU twice weekly, or both, and reported that all three arms produced equivalent testosterone restoration over the trial duration. The implication is that hCG monotherapy is mechanistically and clinically interchangeable with SERM-based pituitary stimulation in this population, and the choice among them is driven by side-effect profile, route, cost, and the patient's view of injection versus oral therapy. The Zucker 2022 retrospective extended the hCG-monotherapy frame to symptomatic men with baseline testosterone above 300 ng/dL (n=31; the symptomatic-but-not-low-T population that increasingly drives the office-visit conversation), reporting symptomatic improvement on the libido and erectile-function axes without significant changes in hematocrit or PSA. The Endocrine Society's 2018 testosterone guideline (Bhasin et al., J Clin Endocrinol Metab 2018, 103:1715–1744) recognizes hCG as appropriate therapy when fertility preservation matters, while continuing to recommend testosterone as first-line for men whose primary concern is symptomatic hypogonadism without a fertility consideration. The broader positioning across the four classes of intervention — TRT, hCG, SERM, and upstream HPG stimulation — is covered in the andropause and peptides dossier.

Pediatric cryptorchidism. Historically, hCG was first-line pharmacological therapy for undescended testis in pre-pubertal boys, on the rationale that LHCGR stimulation drives Leydig-cell androgen production and supports testicular descent. The indication remains in the FDA label, but pediatric urology practice has shifted decisively toward early orchidopexy (surgical correction) as first-line, with hCG use declining substantially over the past two decades. The clinical case for hCG in cryptorchidism is now largely historical.

Female fertility induction. In assisted reproductive technology, hCG is used to trigger final oocyte maturation and ovulation in cycles primed with FSH. The LH-surge mimicry is the mechanistic basis: native ovulation depends on a pituitary LH surge that initiates follicular rupture roughly 36–38 hours later; an hCG bolus delivered at the appropriate point in a stimulated cycle reproduces that signal pharmacologically. Pregnyl, Novarel, Profasi (urinary), and Ovidrel (recombinant choriogonadotropin alfa) are the standard preparations. This is the most extensively used hCG indication globally by volume of doses dispensed, and the indication is uncontroversial within reproductive endocrinology.

The "HCG diet" controversy. A.T.W. Simeons' 1954 protocol — daily hCG injection paired with a 500 kcal/day diet — has been repeatedly resurrected as a commercial weight-loss program, including the over-the-counter "homeopathic" hCG drops that proliferated through the late 2000s. The published literature has been consistent and unambiguous for three decades. The criteria-based meta-analysis Lijesen et al., Br J Clin Pharmacol 1995, 40:237–243 reviewed 24 studies (8 controlled, 16 uncontrolled) of hCG in obesity treatment and concluded that there is no scientific evidence hCG is effective in the treatment of obesity, does not bring about weight loss or fat redistribution, and does not reduce hunger or induce a feeling of well-being. The weight loss observed on the Simeons protocol is entirely attributable to the very-low-calorie diet component; subtract the caloric restriction and the hCG produces nothing. The FDA in December 2011 issued joint warning letters with the FTC to seven companies marketing over-the-counter "homeopathic" hCG products for weight loss, stating that there are no FDA-approved hCG products for weight loss and that these products are unproven and potentially dangerous when paired with the 500-calorie diets their labels recommended. Readers who arrive here from "HCG diet" searches should leave with the same conclusion the literature has held for three decades: it does not work, the weight loss is from the diet, and the FDA does not approve any hCG product for that purpose.