Peptide Hormone / SubQ, IM / 250-500 IU 2-3x per week
HCG
hCG was found in the urine of pregnant women in 1927 and became the first practical pregnancy test before anyone knew what it did in the body. Its two best-known off-label uses ran in opposite directions: the weight-loss protocol, applied mainly to women, was adopted worldwide and then failed every controlled test, while the testicular-rescue protocol, a male use, was worked out on forums and only tested two decades later, at which point it passed.
In plain words
HCG is a hormone the placenta makes during pregnancy. It was found in the urine of pregnant women in 1927 and became the first practical pregnancy test, before anyone knew what it did in the body. It presses the same switch as luteinizing hormone, the pituitary signal that tells the testes to make testosterone, which is why it is prescribed for boys with undescended testicles and for men whose pituitary has failed, and why men taking testosterone use it off-label to keep their testes working. That off-label use has real controlled support: a randomized trial showed low doses held testosterone inside the testis near its normal level even during a complete shutdown, and uncontrolled clinic series afterwards reported preserved sperm counts and recovery. It does nothing for weight loss, though: a double-blind trial found no difference from placebo on any measure, and the US label opens by stating in capitals that it has not been shown to work for obesity. It is banned for male athletes because in men it reliably raises blood testosterone, a ban the cited review found much harder to justify in women.
At a glance
| Half-life | 1.96 days |
|---|---|
| Tmax | 1 days |
| Route(s) | SubQ, IM |
| Published dosing range | 250-500 IU 2-3x per week |
| Vial strengths | 5000, 2000, 10000 IU |
Reference data from the DosePlot canon -- not a protocol recommendation.
Serum curve
Single 375 IU dose by SubQ, rendered from the same engine that powers the interactive chart. Relative levels, not lab values.
What does the evidence show?
Two things are labeled separately here because they answer different questions. The tier is how a study was built. The distance chips are whether that study touched this molecule, by this route, in a population resembling the reader. A randomized trial of a different molecule keeps its tier and still says nothing about this compound.
| Finding | Tier | Distance from use | Study |
|---|---|---|---|
| Low-dose hCG holds testosterone inside the testis during a full testosterone shutdown. Twenty-nine men taking 200 mg testosterone enanthate weekly were randomized to saline or to 125, 250, or 500 IU hCG every other day for three weeks. On testosterone alone, intratesticular testosterone fell 94 percent, from 1234 to 72 nmol/L. With hCG it ended 25 percent below baseline at 125 IU, 7 percent below at 250 IU, and 26 percent above at 500 IU. Baseline serum testosterone was 1.2 percent of the intratesticular concentration, so a serum reading says almost nothing about the level the sperm-producing tissue actually sees. | rct | not recorded | Coviello AD, Matsumoto AM, Bremner WJ, et al. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression.Journal of Clinical Endocrinology and Metabolism 90(5):2595-2602, 2005 |
| Adding hCG to testosterone replacement kept semen parameters intact. In a retrospective series of 26 hypogonadal men on injected or transdermal testosterone plus 500 IU intramuscular hCG every other day, no man became azoospermic and 9 of the 26 contributed to a pregnancy. Mean follow-up was 6.2 months. The paper separately reports that volume, density, motility and forward progression showed no differences during more than a year of follow-up, without stating how many of the 26 were followed that long. The same paper puts the azoospermia rate on testosterone replacement without hCG at about 40 percent. | clinical | not recorded | Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy.Journal of Urology 189(2):647-650, 2013 |
| Restarting sperm production after testosterone use takes an order of magnitude more hCG than maintenance does. In a retrospective case series of 49 men who were azoospermic or severely oligospermic while on exogenous testosterone, 3,000 IU hCG subcutaneously every other day plus clomiphene, tamoxifen, anastrozole, or recombinant FSH restored or improved counts in 47 of 49 (95.9 percent). Mean time to return was 4.6 months at a mean first density of 22.6 million per mL. There was no control arm, so the share of that recovery owed simply to stopping testosterone is not separated out. | clinical | not recorded | Wenker EP, Dupree JM, Langille GM, et al. The use of HCG-based combination therapy for recovery of spermatogenesis after testosterone use.Journal of Sexual Medicine 12(6):1334-1337, 2015 |
| hCG replaces the LH signal and only the LH signal. Thirteen men with gonadotropin deficiency, whose sperm production had first been started with hCG plus menopausal gonadotropin in twelve cases and with GnRH in the thirteenth, were then kept on hCG alone for 3 to 24 months. Sperm remained present in all but one man and testicular volume held at 87 percent of the volume reached on combined treatment, but counts declined steadily over the year. FSH is required for quantitatively normal sperm production, and hCG does not supply it. | clinical | not recorded | Depenbusch M, von Eckardstein S, Simoni M, Nieschlag E. Maintenance of spermatogenesis in hypogonadotropic hypogonadal men with human chorionic gonadotropin alone.European Journal of Endocrinology 147(5):617-624, 2002 |
| The case for the sport ban rests on a narrative clinical review of the existing evidence rather than on a new study. It found unequivocal evidence that in men hCG causes a consistent and sustained rise in blood testosterone, which is the stated reason it is banned in male athletes. The same review found no consistent or biologically significant testosterone rise from hCG in women, and pointed out that routine urinary hCG testing of young women risks invasion of privacy by detecting unrecognized pregnancy, so the prohibition is defensible in men and hard to justify in women. | clinical | not recorded | Handelsman DJ. Clinical review: the rationale for banning human chorionic gonadotropin and estrogen blockers in sport.Journal of Clinical Endocrinology and Metabolism 91(5):1646-1653, 2006 |
| Route hardly changes the hormone response, and less than half the injected dose reaches the blood. Single 125 mcg doses of recombinant hCG given intravenously, intramuscularly, or subcutaneously to down-regulated men produced comparable rises in serum testosterone, inhibin, and estradiol. Absolute bioavailability was 40 to 50 percent for the intramuscular and the subcutaneous route alike, and repeated subcutaneous dosing accumulated about 1.7-fold. DosePlot's stored activity figure of 45 percent sits at the midpoint of that measured range; the reference record itself gives no derivation. | clinical | not recorded | Trinchard-Lugan I, Khan A, Porchet HC, Munafo A. Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers.Reproductive BioMedicine Online 4(2):106-115, 2002 |
| hCG does nothing for weight loss. Fifty-one women were randomized in a 32-day double-blind trial to hCG injections or placebo on an identical 500-calorie diet, weighed six days a week, and counseled by the investigator giving the injections. There was no difference between the groups in weight lost, percent of weight lost, hip or waist circumference, weight lost per injection, or hunger ratings. | rct | not recorded | Stein MR, Julis RE, Peck CC, et al. Ineffectiveness of human chorionic gonadotropin in weight reduction: a double-blind study.American Journal of Clinical Nutrition 29(9):940-948, 1976 |
| Community practice is 250 to 500 IU two or three times a week alongside testosterone, taken to keep testicular size and to make a later restart easier. That is at or below the schedules in the trials behind the practice, which dosed the same 250 to 500 IU every other day. The reported trade-off is a rise in estradiol at the upper end, and the usual advice is to lower the hCG dose rather than add an aromatase inhibitor. | anecdotal | not recorded | community reports aggregated from reddit, MESO-Rx, and similar forumsno study |
How did it get here?
- preclinical1927-1928
- Selmar Aschheim and Bernhard Zondek report a gonad-stimulating substance in the urine of pregnant women. Injected into immature mice, it drives their ovaries to maturity within days. The Aschheim-Zondek reaction becomes the first practical pregnancy test, and for years the animal response is the hormone's only definition: not a structure, not a mass, but what a measured dose does to a rodent gonad.
- first-human1930s
- Crude extracts of pregnancy urine are injected into boys with undescended testicles and into men whose pituitary has failed. Both indications are still printed on the US label today, together with dosing schedules of that vintage, including 4,000 units three times a week for six to nine months.
- clinical-adoption1954
- A T W Simeons publishes in The Lancet that small daily doses of hCG alongside a 500-calorie diet redistribute body fat and abolish hunger. The protocol spreads worldwide under his name and is still sold. No controlled trial has ever supported it. The INDICATIONS AND USAGE section of the US prescribing information for urinary hCG opens with a capitalized statement that hCG has not been demonstrated to be effective adjunctive therapy in the treatment of obesity. In December 2011 the FDA and the FTC issued seven warning letters to companies selling over-the-counter drops, pellets and sprays labeled as homeopathic hCG for weight loss; hCG is a prescription drug and is not approved for over-the-counter sale for any purpose.
- grey-market1980s-1990s
- hCG becomes standard equipment in steroid practice, used during a cycle to keep the testes working and afterwards to restart them. None of that appears in any label, and the doses are settled by trial and error and passed around in print and on forums. Sport governing bodies ban it for male athletes; the endocrine case for banning it in men, and for not banning it in women, is not laid out in the literature until 2006.
- clinical-adoption2000
- The FDA approves choriogonadotropin alfa, grown in Chinese hamster ovary cells instead of collected from urine. It carries the same 92-amino-acid alpha chain and 145-amino-acid beta chain as the natural hormone, and in the registration trials 250 mcg of it stood in for 10,000 USP units of urinary hCG given intramuscularly and for 5,000 IU given subcutaneously.
- clinical-adoption2005-2020
- The controlled data finally arrive, and they arrive for the grey-market use. A randomized dose-response study shows that 250 IU every other day holds intratesticular testosterone near baseline through a complete gonadotropin shutdown; retrospective series then show preserved sperm counts on testosterone plus hCG, and recovery afterwards with hCG-based combinations. Fertility-minded clinics adopt a protocol that had been running unlabeled for twenty years. On March 23, 2020 the transition provision of the Biologics Price Competition and Innovation Act moved protein products including chorionic gonadotropin out of the drug-application system and into biologics licensing. The urinary product's old application number is now carried as a biologics license, and its label prints a US license number.
How is it made?
Production runs along two routes, and they are not the same industry.
1. Collecting it. Urinary hCG is recovered from pooled urine of pregnant women, then adsorbed, precipitated, and purified by chromatography. Nothing is synthesized. The hormone is two chains of 92 and 145 amino acids carrying eight sugar trees, too large and too heavily glycosylated to build by ordinary chemistry, so the placenta stays the factory.
2. Growing it. The recombinant route puts both subunit genes into Chinese hamster ovary cells, which assemble, glycosylate, and secrete the finished dimer into the culture medium; chromatography does the rest. The protein sequence matches the natural hormone exactly. The sugars match closely rather than exactly.
3. Getting the sugars right. The sialic acid capping those sugar trees is what keeps the molecule in the blood, and glycosylation is decided by cell line, culture conditions, and purification. Two batches with identical protein can differ in potency and in half-life, which is why the urinary product is labeled in units of biological activity rather than milligrams of protein. The recombinant product is labeled by mass.
4. Filling the vial. The urinary product is freeze-dried with mannitol in a phosphate buffer, nitrogen gas being used in the freeze-drying step; the recombinant product is filled as a ready-to-use liquid. A protein cake looks identical whether it is full strength, under-filled, or heat-damaged in transit. Potency can only be read out by assay, and that assay is exactly what is missing outside regulated manufacturing.
Worth knowing
The molecule exists because a stop codon was lost. Comparing the single human LH beta gene with the chorionic gonadotropin beta genes shows the hCG beta subunit evolved from an ancestral LH beta gene, and that its 24-amino-acid carboxy-terminal extension arose from a single base deletion which pulled what had been the 3-prime untranslated region into the coding sequence. A stretch of sequence that used to be a switch became a tail, and that tail is the difference between a hormone cleared in an hour or two and one that lasts days.
Talmadge K, Vamvakopoulos NC, Fiddes JC. Evolution of the genes for the beta subunits of human chorionic gonadotropin and luteinizing hormone.Nature 307(5946):37-40, 1984
That tail is probably why pregnancy does not cause hyperthyroidism. hCG is a weak agonist at the TSH receptor, which is what drives thyroid overactivity in trophoblastic tumors and severe hyperemesis. Purified LH is about ten times more potent than hCG at the recombinant human TSH receptor, and a mutant hCG with the C-terminal peptide deleted comes close to LH in potency there. If intact hCG were as thyrotropic as LH, most pregnant women would be thyrotoxic. All four of the beta chain's O-linked sugar chains sit inside that C-terminal peptide, which the same source defines as a 31-amino-acid extension rather than as the 24-residue difference from LH beta.
Yoshimura M, Hershman JM. Thyrotropic action of human chorionic gonadotropin.Thyroid 5(5):425-434, 1995
The unit on the vial is defined by what the hormone does to a rat. Biological activity of the recombinant product is measured by the seminal-vesicle weight-gain test in male rats described in the European Pharmacopoeia monograph and calibrated against the third international reference preparation, and the syringe is then labeled by mass, 250 mcg. In the approval trials that 250 mcg matched 10,000 USP units of urinary hCG given intramuscularly and 5,000 IU given subcutaneously. A vial marked in units and a syringe marked in micrograms are describing the same trigger dose under two conventions.
Ovidrel PreFilled Syringe (choriogonadotropin alfa injection) prescribing information, DESCRIPTION and CLINICAL STUDIES sections.EMD Serono Inc, US FDA label, current version published December 2023
Reconstitution
HCG ships lyophilized and is mixed before use; the published vial strengths are 5000, 2000, 10000 IU. The water volume you add sets the concentration, not the dose -- the calculator turns a vial size and a water volume into mg/mL, draw volume, and units on an insulin syringe.
Open in the reconstitution calculatorWritten and reviewed by Evan Marlow, developer of DosePlot · Updated 2026-08-27
Not medical advice. DosePlot is an informational tool, not a healthcare provider, and using it creates no provider-patient relationship. Do not start, stop, or change any protocol without the approval of a licensed healthcare professional.
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