HCG (chorionic gonadotropin) is a hormone produced by the placenta during pregnancy — the same one a pregnancy test detects. It has been used as a medicine for decades: in women it triggers ovulation, in men whose pituitary fails to produce its hormones it drives the testes to make testosterone and sperm, and in boys it is sometimes used for undescended testes. In biohacking circles it is known mainly for two things: keeping the testes working during testosterone therapy and — entirely without justification — the so-called HCG diet. The evidence is uneven: strong in andrology (physiological studies and a meta-analysis of dozens of papers), based on small non-randomised series when it comes to testosterone therapy, and clearly negative for weight loss. In this review we explain in plain terms what HCG is, how it works and what the research really shows.
What HCG is
HCG is a glycoprotein (a protein with sugars attached) made of two subunits. The alpha subunit is identical to that of the pituitary hormones LH, FSH and TSH; it is the beta subunit that gives the hormone its identity. Beta-HCG carries an extra sugar-laden “tail” at its end that LH lacks — thanks to it the molecule is cleared from the blood much more slowly, so a single injection acts for several days, whereas pituitary LH is released in short pulses. Medicines containing HCG are made from the urine of pregnant women (“urinary” preparations) or by recombinant methods. Although HCG was long treated as an “LH substitute”, the review by Choi and Smitz (2014) shows that the two hormones, despite sharing a receptor, switch on slightly different signalling pathways inside the cell and are not fully interchangeable.
How it works
HCG acts on the same “switch” on cells as LH — the LH/HCG receptor. In a man that switch sits on the Leydig cells of the testes, which respond by producing testosterone. In a woman the same receptor on ovarian cells turns a mature follicle into a corpus luteum and triggers ovulation; during pregnancy placental HCG keeps the corpus luteum and its progesterone production going. Just as important is what HCG does not do: it does not replace FSH, the second pituitary hormone, which acts on Sertoli cells and is needed for quantitatively normal sperm production. That distinction comes back in every study described below.
Testosterone inside the testis versus testosterone in the blood
The key to understanding HCG is that the testosterone concentration inside the testis is many times higher than in the blood. Jarow's team (2001) drew fluid from the testes of 21 fertile men with a needle: on average 609 ng/ml of testosterone, that is more than 100 times the serum level. In the study by Coviello et al. (2005) blood testosterone was 1.2 % of the intratesticular concentration. That high local concentration is required for sperm production. When a man takes testosterone from outside, the pituitary stops releasing LH and FSH, the Leydig cells fall silent and the intratesticular level drops — by 94 % in Coviello's study — despite a normal or even high blood result. Hence the situation where the blood test looks fine and the semen is empty.
Coviello et al. tested in a randomised study of 29 healthy men whether HCG can prevent this. All received 200 mg of testosterone enanthate weekly plus either placebo or one of three HCG doses (125, 250 or 500 IU every other day) for three weeks. Intratesticular testosterone rose linearly with the dose: the lowest dose left it 25 % below baseline, the middle one 7 % below, and the highest 26 % above. The authors' conclusion: a relatively low dose of HCG keeps intratesticular testosterone within the normal range despite a blocked pituitary. Two caveats. First, the study lasted three weeks and measured the hormone, not sperm — whether that level is enough for sperm production was left to later work. Second, it did not test whether higher doses improve semen; the claim that they “only raise the blood level” has no support in this study.
Human data — hypogonadotropic hypogonadism
The strongest evidence concerns men whose pituitary does not release LH and FSH (hypogonadotropic hypogonadism, HH). In a classic paper from the New England Journal of Medicine, Finkel et al. (1985) treated 21 such men with HCG: the sperm count returned to normal in all six whose condition had begun after puberty, but in only one of the fifteen whose condition had begun before it. When the rest were given menopausal gonadotropin (a source of FSH) in addition, semen normalised in five of seven men without a history of undescended testes and in one of seven with it. A meta-analysis of 44 studies (Rastrelli et al., 2014) sums it up: gonadotropins bring sperm into the ejaculate in 75 % of men with HH (range 69–81 %), with a mean concentration of 5.9 million/ml — usually below the normal range, though often enough for conception. The outcome is worse when the condition began before puberty (68 % versus 84 %, 3.4 versus 12.9 million/ml) and better when HCG is combined with FSH than with HCG alone.
Why is HCG alone not enough? A series of physiological studies from Seattle answers that. Matsumoto et al. (1986) gave HCG to eight healthy men for seven months, which switched off their own FSH: sperm concentration fell from 88 to 22 million/ml, that is to about a quarter of normal, although sperm motility and morphology stayed normal. When four of them were then given FSH or menopausal gonadotropin, concentration rose from 34 to 103 million/ml against a control value of 125. The figure of “50 % of normal” popular online does not come from any of these papers — the data point to a clearly lower, though not zero, level that depends on how much FSH the patient still has.
HCG during testosterone therapy
The commonest off-label use today is preserving fertility in men treated with testosterone. The evidence here is surprisingly thin. Hsieh et al. (2013) retrospectively reviewed the records of 26 men (mean age 36) who received testosterone as gel or injections together with HCG 500 IU every other day. Over a mean follow-up of 6.2 months semen parameters did not change, no one became azoospermic, and nine of the 26 fathered a pregnancy. It was, however, a retrospective study from a single centre, without a control group and with short follow-up — it shows the approach is feasible, not that it works for everyone. A reassuring finding comes from the Rastrelli meta-analysis: previous testosterone therapy does not worsen the later response to gonadotropins.
The “HCG diet” — what the research says
In the mid-twentieth century the British physician Albert Simeons combined HCG injections with a very-low-calorie diet and announced that the hormone “releases” fat. The meta-analysis by Lijesen et al. (1995) examined 8 controlled and 16 uncontrolled trials: most were methodologically weak, and of the 12 best only one judged HCG useful. The conclusion was that there is no scientific evidence that HCG causes weight loss, changes fat distribution, reduces hunger or improves well-being. For years the US FDA has required the label of every HCG product to state that the hormone has not been shown to be effective as adjunctive treatment for obesity (drug label). Any weight lost on that diet is the effect of near-starvation, not the hormone.
Safety and the limits of the evidence
HCG is an approved medicine, so its safety profile is set out in the label: in women the most dangerous risk is ovarian hyperstimulation syndrome (sudden ovarian enlargement, fluid in the abdomen, a risk of clots) and multiple pregnancies; arterial thromboembolism and allergic reactions to urine-derived products have been reported in both sexes; in men and boys — oedema, headache, gynaecomastia and precocious puberty. Prostate cancer and other androgen-dependent tumours are contraindications, because HCG raises testosterone. Stimulated Leydig cells also produce estradiol, which explains the gynaecomastia seen with longer use. The limits of the evidence differ from those of most research peptides: there is no shortage of data on how HCG works, but there is a shortage of large randomised trials for off-label uses — Coviello's study had 29 participants, Matsumoto's eight, and the only study of “HCG during testosterone therapy” was retrospective. We deliberately give no methods of use and no doses.
The wider context — the hypothalamus–pituitary–testis axis
HCG is one of several tools acting on the reproductive hormone axis. One level up works kisspeptin, which prompts the pituitary to release its own LH and FSH; alongside HCG stands menotropin (HMG) — a mixture of FSH and LH from the urine of postmenopausal women, added when HCG alone does not rebuild the semen. Only together do they form the full picture, with HCG responsible for intratesticular testosterone and FSH for complete sperm production.
Summary
HCG is a placental hormone that mimics LH and drives the testes to produce testosterone; an approved medicine with more than half a century of literature. Physiological studies have shown that intratesticular testosterone is over a hundred times higher than blood testosterone, that testosterone therapy lowers it by more than 90 %, and that a low dose of HCG can maintain it. In hypogonadotropic hypogonadism gonadotropins restore sperm in three quarters of men, with HCG alone giving a partial result — near-full recovery requires adding FSH. Fertility preservation during testosterone therapy rests on one retrospective series of 26 men, and the “HCG diet” has no support in the research at all. The state of the evidence: strong where HCG is a medicine, weak where it is a fashion.
Sources
- Rastrelli G, Corona G, Mannucci E, Maggi M. Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Andrology. 2014;2(6):794–808. PMID: 25271205. DOI: 10.1111/andr.262. pubmed.ncbi.nlm.nih.gov/25271205
- Coviello AD, Matsumoto AM, Bremner WJ, et al. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. The Journal of Clinical Endocrinology and Metabolism. 2005;90(5):2595–2602. PMID: 15713727. DOI: 10.1210/jc.2004-0802. pubmed.ncbi.nlm.nih.gov/15713727
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- Matsumoto AM, Karpas AE, Bremner WJ. Chronic human chorionic gonadotropin administration in normal men: evidence that follicle-stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man. The Journal of Clinical Endocrinology and Metabolism. 1986;62(6):1184–1192. PMID: 3084535. DOI: 10.1210/jcem-62-6-1184. pubmed.ncbi.nlm.nih.gov/3084535
- Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. The Journal of Urology. 2013;189(2):647–650. PMID: 23260550. DOI: 10.1016/j.juro.2012.09.043. pubmed.ncbi.nlm.nih.gov/23260550
- Jarow JP, Chen H, Rosner TW, et al. Assessment of the androgen environment within the human testis: minimally invasive method to obtain intratesticular fluid. Journal of Andrology. 2001;22(4):640–645. PMID: 11451361. pubmed.ncbi.nlm.nih.gov/11451361
- Lijesen GK, Theeuwen I, Assendelft WJ, Van Der Wal G. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis. British Journal of Clinical Pharmacology. 1995;40(3):237–243. PMID: 8527285. DOI: 10.1111/j.1365-2125.1995.tb05779.x. pubmed.ncbi.nlm.nih.gov/8527285
- Choi J, Smitz J. Luteinizing hormone and human chorionic gonadotropin: origins of difference. Molecular and Cellular Endocrinology. 2014;383(1–2):203–213. PMID: 24365330. DOI: 10.1016/j.mce.2013.12.009. pubmed.ncbi.nlm.nih.gov/24365330
For in-vitro laboratory research only. It is not a human medicine and is not for treatment.