Skip to content
All peptides

HCG

Tier 2 · Preclinical
Also known as Human chorionic gonadotropin · Pregnyl · Ovidrel · Choriogonadotropin alfa

Grounded in tier-1 human clinical and regulatory sources including a randomized assisted-reproduction trial17 and multiple regulatory product monographs/labels (7 through2,4), supplemented by human observational studies and mechanistic/expert reviews. Note that several novel therapeutic proposals (overactive bladder, breast cancer prevention, transplant anti-rejection, osteosarcoma surveillance) rest on single low-tier or exploratory sources, and TRT-adjunct dosing details derive from a single non-regulatory clinician guide.

Half-life
~30 h
Routes
Intramuscular · Subcutaneous
Goals
Fertility and reproductive health · Ovulation induction / assisted reproduction · Male hypogonadism and endogenous testosterone support · Cryptorchidism treatment · Pregnancy maintenance / diagnostic and tumor marker
Cost / mg
Not recorded

How it works

HCG is a hormone normally made by the placenta during pregnancy. It is built from two pieces (an alpha subunit shared with the pituitary hormones LH, FSH and TSH, and a unique beta subunit). HCG acts almost like the body's own luteinizing hormone (LH): it plugs into the LH receptor on the testes and ovaries and tells them to make sex hormones — androgens (testosterone) in men and progesterone in women. Because it mimics LH so closely, it is used to trigger ovulation, to stimulate testosterone and sperm production, and to help undescended testicles drop in boys. In pregnancy it keeps the corpus luteum producing progesterone so the pregnancy is maintained, and it is the molecule detected by pregnancy tests. Regulatory labels are explicit that HCG has no known effect on fat, appetite or body-fat distribution and has not been shown to help weight loss.

Overview

Overview

HCG (human chorionic gonadotropin) is a placental polypeptide/glycoprotein hormone marketed under names including Pregnyl, Ovidrel and choriogonadotropin alfa. It is a heterodimer of an alpha subunit — essentially identical to the alpha subunits of the pituitary gonadotropins LH and FSH and of TSH — and a unique beta subunit bearing an extended carboxy-terminal peptide (CTP). The intact molecule is roughly 36.7 kDa and 237 amino acids, with carbohydrate side chains making up 25-40% of its mass.

Physiological role

HCG is the first molecule synthesized by the embryo (hCG RNA is transcribed as early as the eight-cell stage, and the blastocyst produces hCG protein before implantation). During normal pregnancy, placental HCG maintains the corpus luteum after LH declines, sustaining estrogen and progesterone secretion and preventing menstruation. It also has angiogenic activity in the uterine endothelium, maintains myometrial quiescence, and exerts immunomodulatory effects that support implantation. hCG becomes detectable 3-7 days post-conception, typically doubles every 48-72 hours in the first 6 weeks, plateaus near week 20, and returns to prepregnancy levels after delivery, miscarriage or termination. Normal levels in males and non-pregnant females are <2 IU/L.

Mechanism

HCG's action is described as virtually identical to pituitary LH (with a small degree of FSH activity). It binds the LH/chorionic gonadotropin receptor (LHCGR), a G protein-coupled receptor, activating adenylyl cyclase and raising cAMP to drive conversion of cholesterol to pregnenolone. This stimulates Leydig cells of the testis to make androgens and the corpus luteum to make progesterone. Additional cascades (Smad2, PKC, PKA) have been reported. Importantly, emerging tier-1 evidence argues that despite sharing a receptor, LH and hCG are not as interchangeable as once believed and have some disparate downstream signaling. HCG does not require a functioning pituitary to work and, unlike clomiphene or anastrozole, does not increase FSH production.

Clinical uses

Approved/established indications include:

  • Prepubertal cryptorchidism not due to anatomic obstruction (therapy usually between ages 4 and 9). Testicular descent is usually reversible on discontinuation, though occasionally permanent.
  • Hypogonadotropic hypogonadism in males (secondary to pituitary deficiency); HCG helps produce testosterone and sperm and can raise endogenous testosterone.
  • Induction of ovulation and pregnancy in appropriately pretreated anovulatory infertile women (with secondary, not primary, ovarian failure), typically following menotropin/FSH preparations.

One Canadian monograph additionally lists delayed adolescence, pituitary dwarfism, and hypogonadotropic eunuchoidism; HCG has produced acceleration of bone growth and sexual/somatic maturation in some pituitary-dwarfism cases.

Diagnostic and marker roles

hCG is the basis of pregnancy testing (including strip tests) and serves as a tumor marker for trophoblastic and some non-trophoblastic cancers. Specific beta-hCG measurement is used in Down's syndrome screening and diagnosis of non-trophoblastic cancer, and beta-hCG has been described as a rare paraneoplastic surveillance marker (e.g., osteosarcoma). Placental heterodimeric HCG has been reported to imprint a protective genomic signature against breast cancer, whereas ectopically expressed beta-HCG in tumors is associated with poor prognosis. hCG is also used in doping control in males, and assay interpretation is complicated by multiple molecular forms.

Exploratory / proposed uses

Several proposals rest on single or exploratory sources and are not established clinical uses: potential treatment of overactive bladder (human detrusor contains hCG receptors and becomes quiescent in pregnancy), breast cancer prevention/therapy, and an anti-rejection role in solid organ transplantation.

Important negative claim

Multiple regulatory labels state explicitly that HCG has no known effect on fat mobilization, appetite or sense of hunger, or body-fat distribution, and that it has not been demonstrated effective for obesity or to increase weight loss beyond caloric restriction — directly contradicting popular 'HCG diet' marketing.

What the research shows

247 findings extracted from the 27 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 2 human trial findings, 24 human study findings, 9 expert opinion findings and 2 theoretical findings.

  • human trialMean numbers of oocytes retrieved per treatment group were equivalent, 13.6, 14.6, and 13.7 with 250 microg of recombinant hCG, 500 microg of recombinant hCG, and urinary hCG, respectively17

  • human trialThe numbers of 2PN fertilized oocytes on day 1 after oocyte retrieval, and 2PN or cleaved embryos on the day of embryo transfer, were significantly higher with 500 microg of recombinant hCG than with the lower dose17

  • human studyAndrogen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present1

  • human studyThis descent is usually reversible when HCG is discontinued1

  • human studyHCG HAS NOT BEEN DEMONSTRATED TO BE EFFECTIVE ADJUNCTIVE THERAPY IN THE TREATMENT OF OBESITY1

  • human studyTHERE IS NO SUBSTANTIAL EVIDENCE THAT IT INCREASES WEIGHT LOSS BEYOND THAT RESULTING FROM CALORIC RESTRICTION, THAT IT CAUSES A MORE ATTRACTIVE OR 'NORMAL' DISTRIBUTION OF FAT, OR THAT IT DECREASES THE HUNGER AND DISCOMFORT ASSOCIATED WITH CALORIE-RESTRICTED DIETS1

  • human studyIn some cases, descent following HCG administration is permanent, in most cases, the response is temporary1

  • human studyAndrogen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present1

Show 29 more findings
  • human studyTHERE IS NO SUBSTANTIAL EVIDENCE THAT IT INCREASES WEIGHT LOSS BEYOND THAT RESULTING FROM CALORIC RESTRICTION, THAT IT CAUSES A MORE ATTRACTIVE OR NORMAL DISTRIBUTION OF FAT, OR THAT IT DECREASES THE HUNGER AND DISCOMFORT ASSOCIATED WITH CALORIE-RESTRICTED DIETS1

  • human studyAndrogen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present4

  • human studyThis descent is usually reversible when HCG is discontinued4

  • human studyHCG HAS NOT BEEN DEMONSTRATED TO BE EFFECTIVE ADJUNCTIVE THERAPY IN THE TREATMENT OF OBESITY4

  • human studyTHERE IS NO SUBSTANTIAL EVIDENCE THAT IT INCREASES WEIGHT LOSS BEYOND THAT RESULTING FROM CALORIC RESTRICTION, THAT IT CAUSES A MORE ATTRACTIVE OR 'NORMAL' DISTRIBUTION OF FAT, OR THAT IT DECREASES THE HUNGER AND DISCOMFORT ASSOCIATED WITH CALORIE-RESTRICTED DIETS4

  • human studyhCG represents a key embryonic signal that is essential for the maintenance of pregnancy5

  • human studyNormal level for hCG in males and nonpregnant females is < 2 IU/L6

  • human studyTransvaginal ultrasound should detect a gestational sac when serum hCG is ≥ 1000-2000 IU/L6

  • human studyhCG affects miscarriage outcomes10

  • human studyhCG affects thyroid function10

  • human studyhCG is no longer a single, omnipotent ovulation triggering option13

  • human studyLuteinizing hormone (LH) and human chorionic gonadotropin (hCG) are widely recognized for their roles in ovulation and the support of early pregnancy15

  • human studyInherited hCG is a source of persistent low concentrations of hCG16

  • human studyFour cases of inherited hCG were identified with similar hCG production recorded in first degree relatives16

  • human studyAll cases produced primarily the regular hCG dimer16

  • human studyIn 1 case hCG was detected only in the urine sample16

  • human studyPregnancy is a protective factor against breast cancer21

  • human studyEctopic expression of β-HCG in various cancer entities is associated with poor prognosis due to its tumor-promoting function21

  • expert opinionAndrogen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present3

  • expert opinionThis descent is usually reversible when hCG is discontinued3

  • expert opinionhCG has not been shown to be an effective adjunctive therapy in the treatment of obesity3

  • expert opinionThere is no substantial evidence that it increases weight loss beyond that resulting from caloric restriction, that it produces a more attractive or 'normal' distribution of fat, or that it reduces the hunger and discomfort associated with calorie-restricted diets3

  • expert opinionTherapy has produced acceleration of longitudinal bone growth as well as sexual and somatic maturation in some cases3

  • expert opinionThe response to hCG is usually dramatic in patients of pubertal age3

  • expert opinionhCG has not been demonstrated to be effective adjunctive therapy in the treatment of obesity8

  • expert opinionThere is no substantial evidence that it increases weight loss beyond that resulting from caloric restriction, that it causes a more attractive or normal distribution of fat, or that it decreases the hunger and discomfort associated with calorie-restricted diets8

  • expert opinionSpecific determination of hCGβ is of value in screening for Down's syndrome and diagnosis of nontrophoblastic cancer23

  • theoreticalHCG HAS NOT BEEN DEMONSTRATED TO BE EFFECTIVE ADJUNCTIVE THERAPY IN THE TREATMENT OF OBESITY7

  • theoreticalThere is no substantial evidence that HCG increases weight loss beyond that resulting from caloric restriction7

How it works

Based on 1 human trial finding, 41 human study findings, 2 animal findings, 1 in vitro finding, 26 expert opinion findings and 22 theoretical findings.

  • human trialHuman Chorionic Gonadotropin (hCG) is a heterodimeric glycoprotein composed of two subunits12

  • human studyThe action of HCG is virtually identical to that of pituitary LH, although HCG appears to have a small degree of FSH activity as well4

  • human studyHCG stimulates production of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce androgens and the corpus luteum of the ovary to produce progesterone4

  • human studyHCG can substitute for LH in the development and maturation of the normal ovarian follicle, and the mid-cycle LH surge triggers ovulation4

  • human studyDuring a normal pregnancy, HCG secreted by the placenta maintains the corpus luteum after LH secretion decreases, supporting continued secretion of estrogen and progesterone and preventing menstruation4

  • human studyHuman chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts5

  • human studyhCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR)5

  • human studyhCG can activate signaling cascades potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR)5

Show 85 more findings
  • human studyhCG displays specialized roles in promoting angiogenesis in the uterine endothelium5

  • human studyhCG maintains myometrial quiescence5

  • human studyhCG is produced during pregnancy and can support pregnancy by allowing for the production of progesterone, which can help in preparing the lining of the uterus for implantation6

  • human studyhCG is a dimer consisting of a 145-amino-acid β subunit that is unique to hCG and a 92-amino-acid α subunit6

  • human studyThe α subunit is identical to that of luteinizing hormone (LH), follicle-stimulating hormone, and thyroid-stimulating hormone6

  • human studyThe α and β subunits have separate genes on separate chromosomes (chromosomes 6 and 19, respectively)6

  • human studyhCG's primary function is to support the corpus luteum in producing progesterone, which is vital for maintaining early pregnancy6

  • human studyhCG exhibits immunomodulatory effects, supporting implantation and modulating the maternal immune response6

  • human studyCarbohydrate side chains comprise 25-40% of the molecular weight of hCG6

  • human studyHCG helps produce testosterone and sperm9

  • human studyHCG treats irregular or absent ovulation in people trying to get pregnant by helping the body release an egg (ovulation)9

  • human studyClassical hCG is the first molecule synthesized by the embryo10

  • human studyhCG RNA is transcribed as early as the eight-cell stage10

  • human studyThe blastocyst produces hCG protein before its implantation10

  • human studyhCG has four major isoforms: classical hCG, hyperglycosylated hCG, free β subunit, and sulphated hCG10

  • human studyhCG has angiogenetic activity10

  • human studyhCG has immunological actions10

  • human studyhCG serves as one of the first signals provided by the embryo to the mother11

  • human studyThe embryonic tissue starts to actively secrete hCG at the time when the first step of the implantation process is initiated and the blastocyst adheres to the maternal endometrium11

  • human studyhCG has critical function for embryo implantation and placentation11

  • human studyhCG regulates biological aspects of early pregnancy events11

  • human studyhCG supports maternal immune cells in their function as helpers in the establishment of an adequate embryo-endometrial relationship11

  • human studyhCG can influence both local uterine immune cell populations as well as peripheral ones due to its early presence in the maternal circulation11

  • human studyGnRH agonist enables successful ovum maturation13

  • human studyhCG supports the luteal phase and pregnancy until placental shift13

  • human studyhCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive tract, both in gonadal and extra-gonadal tissues14

  • human studyhCG promotes oocyte maturation, fertilization, implantation and early embryo development14

  • human studyLH and hCG have similar molecular structures and share a common receptor15

  • human studyLH and hCG are not as interchangeable as once believed despite similar molecular structures and shared receptor15

  • human studyAlthough LH and hCG bind to a common receptor, emerging evidence suggests that LH and hCG have disparate effects on downstream signaling cascades15

  • human studyβ-hCG production by osteosarcoma cells was confirmed via pathology and gene expression studies20

  • human studyPlacental HCG and ectopically expressed β-HCG exert opposite effects on breast tumorigenesis21

  • human studyhuman detrusor muscle contains hCG receptors22

  • human studydetrusor muscle becomes quiescent during pregnancy22

  • animalhCG can inhibit detrusor muscle contractions induced by cholinergic stimulation in rats22

  • animalhCG can mimic the anticholinergic drug on detrusor muscle contractions22

  • in vitroPlacental heterodimeric HCG acts as a protective agent by imprinting a permanent genomic signature of the mammary gland determining a refractory condition to malignant transformation which is characterized by cellular differentiation, apoptosis and growth inhibition21

  • expert opinionHuman chorionic gonadotropin (HCG), a polypeptide hormone produced by the human placenta, is composed of an alpha and a beta sub-unit1

  • expert opinionThe alpha sub-unit is essentially identical to the alpha sub-units of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to the alpha sub-unit of human thyroid-stimulating hormone (TSH)1

  • expert opinionThe action of HCG is virtually identical to that of pituitary LH, although HCG appears to have a small degree of FSH activity as well1

  • expert opinionHCG stimulates production of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce androgens and the corpus luteum of the ovary to produce progesterone1

  • expert opinionHCG HAS NO KNOWN EFFECT ON FAT MOBILIZATION, APPETITE OR SENSE OF HUNGER, OR BODY FAT DISTRIBUTION1

  • expert opinionHuman chorionic gonadotropin (HCG) is a polypeptide hormone produced by the human placenta, composed of an alpha and a beta subunit1

  • expert opinionThe alpha subunit is essentially identical to the alpha subunits of human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and to the alpha subunit of human thyroid-stimulating hormone (TSH)1

  • expert opinionThe action of HCG is virtually identical to that of pituitary LH, although HCG appears to have a small degree of FSH activity as well1

  • expert opinionHCG stimulates production of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce androgens and the corpus luteum of the ovary to produce progesterone1

  • expert opinionChorionic Gonadotropin for Injection, USP (hCG) is extracted from the urine of pregnant women3

  • expert opinionhCG is a water-soluble polypeptide hormone produced by the human placenta composed of an alpha and a beta sub-unit3

  • expert opinionThe alpha sub-unit is essentially identical to the alpha sub-units of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), as well as to the alpha sub-unit of human thyroid-stimulating hormone (TSH)3

  • expert opinionThe action of hCG is virtually identical to that of pituitary LH, although hCG appears to have a small degree of FSH activity as well3

  • expert opinionHCG can substitute for LH in ovulation triggering function during the normal menstrual cycle3

  • expert opinionDuring a normal pregnancy, hCG secreted by the placenta maintains the corpus luteum after LH secretion decreases, supporting continued secretion of estrogen and progesterone and preventing menstruation3

  • expert opinionhCG action is virtually identical to that of pituitary LH, although hCG appears to have a small degree of FSH activity as well8

  • expert opinionhCG stimulates production of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce androgens and the corpus luteum of the ovary to produce progesterone8

  • expert opinionAndrogen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present8

  • expert opinionHCG has no known effect on fat mobilization, appetite or sense of hunger, or body fat distribution8

  • expert opinionRegular hCG may be produced by the pituitary gland either as excess pituitary production beyond that which occurs alongside the LH peak in every menstrual cycle or as a genetic disorder16

  • expert opinionThe main form of hCG in circulation and in patients with trophoblastic tumors is intact heterodimeric hCG23

  • expert opinionThe free β subunit (hCGβ) is a minor form in plasma in both conditions, but it may be the major form in aggressive trophoblastic cancer23

  • expert opinionHCG has a similar structure and essentially the same hormonal action as LH25

  • expert opinionHCG works by increasing LH activity25

  • expert opinionHCG does not require a functioning pituitary gland to work effectively25

  • expert opinionUnlike clomiphene and anastrazole, HCG does not increase FSH production25

  • theoreticalHuman chorionic gonadotropin (HCG) is a polypeptide hormone produced by the human placenta, composed of an alpha and a beta sub-unit4

  • theoreticalThe alpha sub-unit is essentially identical to the alpha sub-units of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and to the alpha sub-unit of human thyroid-stimulating hormone (TSH)4

  • theoreticalHuman chorionic gonadotropin (HCG) is a polypeptide hormone produced by the human placenta, composed of an alpha and a beta subunit7

  • theoreticalThe alpha subunit of HCG is essentially identical to the alpha subunits of human pituitary gonadotropins LH and FSH, as well as to the alpha subunit of human TSH7

  • theoreticalHCG action is virtually identical to that of pituitary LH, although HCG appears to have a small degree of FSH activity as well7

  • theoreticalHCG stimulates production of gonadal steroid hormones by stimulating the interstitial cells (Leydig cells) of the testis to produce androgens and the corpus luteum of the ovary to produce progesterone7

  • theoreticalAndrogen stimulation in the male leads to the development of secondary sex characteristics and may stimulate testicular descent when no anatomical impediment to descent is present7

  • theoreticalThis descent is usually reversible when HCG is discontinued7

  • theoreticalHCG can substitute for LH in the development and maturation of the normal ovarian follicle, and the mid-cycle LH surge triggers ovulation7

  • theoreticalDuring a normal pregnancy, HCG secreted by the placenta maintains the corpus luteum after LH secretion decreases, supporting continued secretion of estrogen and progesterone, and preventing menstruation7

  • theoreticalHCG HAS NO KNOWN EFFECT ON FAT MOBILIZATION, APPETITE OR SENSE OF HUNGER, OR BODY FAT DISTRIBUTION7

  • theoreticalHuman chorionic gonadotrophin interacts with the same receptors on luteal cells as does LH18

  • theoreticalHuman chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo26

  • theoreticalThe pituitary analogue of hCG, luteinizing hormone (LH), is produced in the pituitary gland of males and females of all ages26

  • theoreticalHuman chorionic gonadotropin is a glycoprotein composed of 237 amino acids with a molecular mass of 36.7 kDa, approximately 14.5kDa αhCG and 22.2kDa βhCG26

  • theoreticalThe α (alpha) subunit is identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH)26

  • theoreticalThe α (alpha) subunit is 92 amino acids long26

  • theoreticalThe β-subunit of hCG gonadotropin (beta-hCG) contains 145 amino acids, encoded by six highly homologous genes on chromosome 19q13.326

  • theoreticalHuman chorionic gonadotropin interacts with the LHCG receptor of the ovary and promotes the maintenance of the corpus luteum for the maternal recognition of pregnancy26

  • theoreticalhCG-treated endometrial cells induce an increase in T cell apoptosis (dissolution of T cells)26

  • theoreticalHCG is a glycoprotein secreted by placental trophoblast cells in pregnancy27

  • theoreticalHCG is a heterodimer composed of two different α- and β-subunits, with the latter being unique to HCG27

Dosing

Based on 9 human trial findings, 1 human study finding, 4 expert opinion findings and 1 theoretical finding.

  • human trialHCG 5000 to 10,000 units IM once 1 day following the last dose of menotropins for ovulation induction2

  • human trialRecombinant Chorionic Gonadotropin (r-HCG) 250 mcg subcutaneously once 1 day following last dose of follicle-stimulating agent for ovulation induction2

  • human trialHCG 500 to 1000 units IM 3 times a week for 3 weeks, then 500 to 1000 units IM 2 times a week for 3 weeks for hypogonadism in males2

  • human trialHCG 4000 units IM 3 times a week for 6 to 9 months, then 2000 units IM 3 times a week for 3 months for hypogonadism in males2

  • human trialHCG 4000 units IM 3 times a week for 3 weeks for prepubertal cryptorchidism in children 4 years and older2

  • human trialHCG 5000 units IM every other day for 4 injections for prepubertal cryptorchidism in children 4 years and older2

  • human trialHCG 500 to 1000 units IM for 15 injections over a period of 6 weeks for prepubertal cryptorchidism in children 4 years and older2

  • human trialHCG 500 units IM 3 times a week for 4 to 6 weeks for prepubertal cryptorchidism in children 4 years and older2

Show 7 more findings
  • human trialRecombinant hCG (250 microg) SC is equivalent to 10,000 U USP of urinary hCG in the indication of final follicular maturation and luteinization in assisted reproduction technology17

  • human studyIn most cases, the response is temporary; therapy is usually instituted between the ages four and nine4

  • expert opinionTherapy is usually instituted between the ages four and nine1

  • expert opinionThis medication is either injected into a muscle or under the skin9

  • expert opinionMedication should be taken as directed on the prescription label at the same time every day9

  • expert opinionHCG must be given by injection, typically 3 times per week subcutaneously25

  • theoreticalWhen reconstituted with Bacteriostatic Water for Injection preserved with benzyl alcohol 0.9%, the solution should be refrigerated and used within 30 days7

How the body handles it

Based on 9 human study findings, 1 in vitro finding, 7 expert opinion findings and 3 theoretical findings.

  • human studyhCG becomes detectable as early as 3-7 days post-conception and typically doubles every 48-72 h during the first 6 weeks of gestation6

  • human studyhCG values plateau around the 20th week and return to prepregnancy levels after delivery, miscarriage, or termination6

  • human studyFollowing IM administration, an increase in serum chorionic gonadotropin concentrations may be observed within 2 hours8

  • human studyPeak concentrations occur within 6 hours and persist for approximately 36 hours8

  • human studySerum chorionic gonadotropin levels begin to decline at 48 hours reaching undetectable levels after 72 hours8

  • human studyThe initial phase half-life has been reported between 5.6 and 11 hours, whereas the terminal phase half-life has been reported between 23 and 37.2 hours8

  • human studyFollowing IM administration of therapeutic doses, approximately 10-12% of the dose is excreted in urine within 24 hours8

  • human studyChorionic gonadotropin is distributed primarily in the testes and ovaries of the male and female respectively, with small amounts possible distributing into the proximal tubules of the renal cortex8

Show 12 more findings
  • human studyhCG concentration steadily increases throughout early pregnancy as it is continuously released by the forming placenta11

  • in vitroAfter SC and IM administration of hCG conventional formulation, it has an average 32-33 h elimination half-life irrespective of the treatment regimen19

  • expert opinionNOVAREL (chorionic gonadotropin) for injection is a water soluble glycoprotein derived from human pregnancy urine and administered intramuscularly after reconstitution1

  • expert opinionAssay of hCG is complicated by the occurrence of different molecular forms, which are detected to various degrees by different assays23

  • expert opinionWhen excreted into urine, most of hCG (and hCGβ) is broken down to the core fragment of hCGβ (hCGβcf), which is the main immunoreactive form of hCG in urine during pregnancy23

  • expert opinionhCGβcf is of limited utility but it is important because it may disturb assay of hCG in pregnancy23

  • expert opinionHCG has a much longer half-life (30 hours) than LH (30 minutes)25

  • expert opinionPeak onset of increased testosterone is about 72-96 hours after administration25

  • expert opinionBlood LH levels often do not increase in men taking HCG due to lack of cross-reactivity with most commercial laboratory assays25

  • theoreticalNOVAREL is derived from human pregnancy urine and administered intramuscularly after reconstitution7

  • theoreticalHCG has a relatively long plasma half-life of 24-36 hours18

  • theoreticalbeta-hCG is mostly similar to beta-LH, with the exception of a Carboxy Terminus Peptide (beta-CTP) containing four glycosylated serine residues that is responsible for hCG's longer half-life26

Safety and side effects

Based on 1 human trial finding, 17 human study findings, 2 animal findings, 10 expert opinion findings and 2 theoretical findings.

  • human trialThe incidence of adverse events also tended to be higher with the 500 microg dose17

  • human studyOvarian hyperstimulation is a principal serious adverse reaction, characterized by sudden ovarian enlargement, ascites with or without pain and/or pleural effusion1

  • human studyRupture of ovarian cysts with resultant hemoperitoneum is a principal serious adverse reaction1

  • human studyMultiple births is a principal serious adverse reaction1

  • human studyArterial thromboembolism is a principal serious adverse reaction1

  • human studyAnaphylaxis and other hypersensitivity reactions have been reported with urinary-derived HCG products1

  • human studyInduction of androgen secretion by HCG may induce precocious puberty in patients treated for cryptorchidism1

  • human studyPrincipal serious adverse reactions during HCG use with human menopausal gonadotropins are: ovarian hyperstimulation, enlargement of preexisting ovarian cysts or rupture of ovarian cysts with resultant hemoperitoneum, multiple births, and arterial thromboembolism1

Show 24 more findings
  • human studyHCG HAS NO KNOWN EFFECT ON FAT MOBILIZATION, APPETITE OR SENSE OF HUNGER, OR BODY FAT DISTRIBUTION4

  • human studyContraindicated in precocious puberty, prostatic carcinoma or other androgen-dependent neoplasm, and prior allergic reaction to HCG4

  • human studyPrincipal serious adverse reactions include ovarian hyperstimulation, rupture of ovarian cysts with resultant hemoperitoneum, multiple births, and arterial thromboembolism4

  • human studyAnaphylaxis and other hypersensitivity reactions have been reported with urinary-derived HCG products4

  • human studyInduction of androgen secretion by HCG may induce precocious puberty in patients treated for cryptorchidism4

  • human studyPrincipal serious adverse reactions include ovarian hyperstimulation, enlargement or rupture of preexisting ovarian cysts, multiple births, and arterial thromboembolism7

  • human studyAnaphylaxis has been reported with urinary-derived HCG products7

  • human studyAnaphylaxis and other hypersensitivity reactions have been reported with urinary derived HCG products8

  • human studyHypersensitivity reactions, both generalized and local; anaphylaxis; and angioedema have been reported8

  • human studySide effects include allergic reactions (skin rash, itching, hives, swelling of the face, lips, tongue, or throat) and blood clot (pain, swelling)9

  • animalCombined HCG/PMS therapy has been noted to induce high incidences of external congenital anomalies in the offspring of mice, in a dose-dependent manner1

  • animalCombined HCG/PMS therapy has been noted to induce high incidences of external congenital anomalies in the offspring of mice in a dose-dependent manner7

  • expert opinionContraindications include precocious puberty, prostatic carcinoma or other androgen-dependent neoplasm, prior allergic reaction to HCG1

  • expert opinionSince androgens may cause fluid retention, HCG should be used with caution in patients with cardiac or renal disease, epilepsy, migraine or asthma1

  • expert opinionHCG HAS NO KNOWN EFFECT ON FAT MOBILIZATION, APPETITE OR SENSE OF HUNGER, OR BODY FAT DISTRIBUTION1

  • expert opinionContraindications include precocious puberty, prostatic carcinoma or other androgen-dependent neoplasm, prior allergic reaction to HCG1

  • expert opinionHCG may cause fetal harm when administered to a pregnant woman1

  • expert opinionSafety and efficacy of HCG have not been established in patients younger than 4 years2

  • expert opinionSafety and efficacy of r-HCG gonadotropin have not been established in children2

  • expert opinionHCG has no known effect on fat mobilization, appetite or sense of hunger, or body fat distribution3

  • expert opinionHerbal or dietary supplements such as blue cohosh, black cohosh, or chasteberry may interact with this medication9

  • expert opinionHCG can increase estradiol to abnormally high levels in some men through conversion of testosterone to estradiol by aromatase enzyme25

  • theoreticalContraindications include precocious puberty, prostatic carcinoma or other androgen dependent neoplasm, and prior allergic reaction to HCG7

  • theoreticalHCG may cause fetal harm when administered to a pregnant woman7

What people use it for

Based on 4 human trial findings, 12 human study findings, 25 expert opinion findings and 6 theoretical findings.

  • human trialHCG is used to cause ovulation and to treat infertility in women2

  • human trialHCG is used for hypogonadism in males2

  • human trialHCG is used for prepubertal cryptorchidism2

  • human trialRecombinant hCG is effective and well tolerated in the induction of final follicular maturation and luteinization in women undergoing assisted reproduction technology17

  • human studyHCG is indicated for prepubertal cryptorchidism not due to anatomic obstruction, with therapy usually instituted between the ages of 4 and 91

  • human studyHCG is indicated for selected cases of hypogonadotropic hypogonadism in males1

  • human studyHCG is indicated for induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who has been appropriately pretreated with human menotropins1

  • human studyHCG is thought to induce testicular descent in situations when descent would have occurred at puberty and may help predict whether or not orchiopexy will be needed in the future4

Show 39 more findings
  • human studyHCG is indicated for selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males4

  • human studyHCG is indicated for induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who has been appropriately pretreated with human menotropins4

  • human studyHCG injections can increase a person's chances of pregnancy9

  • human studyHCG treats a condition that affects the testes called cryptorchidism9

  • human studyHCG may be used to treat low sperm count by helping the body make more testosterone and sperm9

  • human studyHCG can be used to treat undescended testicles by helping one or both testicles move into the scrotum9

  • human studyThis medication may be prescribed for children as young as several months of age for selected conditions9

  • human studyGnRH agonist followed by hCG triggering represents a new era of administering these agents13

  • expert opinionHCG is thought to induce testicular descent in situations when descent would have occurred at puberty1

  • expert opinionHCG indicated for selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males1

  • expert opinionHCG indicated for induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who has been appropriately pretreated with human menotropins1

  • expert opinionHCG HAS NOT BEEN DEMONSTRATED TO BE EFFECTIVE ADJUNCTIVE THERAPY IN THE TREATMENT OF OBESITY1

  • expert opinionhCG is given to males in an effort to stimulate the interstitial cells of the testes (cells of Leydig) to produce androgen3

  • expert opinionhCG is given in the second phase of the cycle in an effort to maintain the functional integrity of the corpus luteum and to stimulate its secretion of progesterone3

  • expert opinionhCG is indicated for the treatment of Prepubertal Cryptorchidism (not due to anatomical obstruction)3

  • expert opinionhCG is indicated for the treatment of Delayed Adolescence3

  • expert opinionhCG is indicated for the treatment of Dwarfism (pituitary)3

  • expert opinionhCG is indicated for the treatment of Hypogonadotropic Eunuchoidism3

  • expert opinionPregnyl is indicated for prepubertal cryptorchidism not due to anatomical obstruction8

  • expert opinionPregnyl is indicated for selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males8

  • expert opinionPregnyl is indicated for induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not due to primary ovarian failure, and who has been appropriately pretreated with FSH-containing preparations8

  • expert opinionhCG seems to have a potential role as an anti-rejection agent in solid organ transplantation14

  • expert opinionIncreased understanding of the inherent differences between LH and hCG will support the individualization of treatment strategies for conditions such as infertility15

  • expert opinionβ-hCG may be a useful surveillance marker to monitor disease progression or recurrence20

  • expert opinionMimicking pregnancy by treatment with HCG is suggested as a strategy for breast cancer prevention21

  • expert opinionTargeting β-HCG expressing tumor cells seems to be an option for breast cancer therapy21

  • expert opinionDetermination of human chorionic gonadotropin (hCG) is used for diagnosis and monitoring of pregnancy, pregnancy related disorders, for trophoblastic and some nontrophoblastic tumors23

  • expert opinionhCG is determined for doping control in males23

  • expert opinionAssays measuring hCG and hCGβ together are mainly used for diagnosis of pregnancy and trophoblastic diseases23

  • expert opinionIf LH is already elevated (over 20 IU/L) then HCG will likely not be effective at increasing testosterone levels25

  • expert opinionHCG works to increase endogenous production of testosterone25

  • expert opinionHCG is the most important diagnostic markers for pregnancy27

  • expert opinionHCG is also a tumor marker27

  • theoreticalHCG is indicated for prepubertal cryptorchidism not due to anatomic obstruction, typically instituted between ages 4 and 97

  • theoreticalHCG is indicated for selected cases of hypogonadotropic hypogonadism in males7

  • theoreticalHCG is indicated for induction of ovulation and pregnancy in anovulatory infertile women pretreated with human menotropins7

  • theoreticalhCG has therapeutic potential for treatment of overactive bladder (OAB)22

  • theoreticalThe presence of hCG is detected in some pregnancy tests (HCG pregnancy strip tests)26

  • theoreticalSome cancerous tumors produce this hormone; elevated levels measured when the patient is not pregnant may lead to a diagnosis of cancer26

Other findings

Based on 1 human study finding and 2 expert opinion findings.

  • human studySecretion of beta human chorionic gonadotropin (β-hCG) is a rare, recently recognised paraneoplastic syndrome20

  • expert opinionChorionic gonadotropin is obtained from the human pregnancy urine1

  • expert opinionHCG is extracted from the urine of pregnant women25

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Contested

Reported HCG half-life values vary across sources

The regulatory monograph reports a two-phase half-life (initial 5.6-11 h, terminal 23-37.2 h) (Submission Control No: 230449 Merck Sharp & Dohme B.V. Used under license.), while review/secondary sources cite 24-36 h (Human Chorionic Gonadotropin - an overview), ~30 h vs 30 min for LH (HCG / Human Chorionic Gonadotropin for Male Infertility — Male Infertility Guide), and 32-33 h elimination for SC/IM conventional formulation (Time–concentration plot of human chorionic gonadotrophin ...). These partly reflect different measurement phases rather than direct disagreement, but readers should note the spread.

Single source

Several novel therapeutic uses rest on single, often low-tier or exploratory sources

Overactive bladder potential (Therapeutic Potential of Human Chorionic Gonadotropin Against Overactive Bladder., includes rat data), breast cancer prevention/therapy (Human Chorionic Gonadotropin and Breast Cancer.), solid organ transplant anti-rejection (Human Chorionic Gonadotropin: The Pregnancy Hormone and More.), and osteosarcoma surveillance marker (Human chorionic gonadotropin-secreting osteosarcoma.) each derive from a single review or study and are exploratory, not established clinical uses.

Single source

TRT-adjunct dosing and estradiol/aromatase details come from one non-regulatory source

Claims about 3x/week SC dosing for endogenous testosterone, ineffectiveness when LH >20 IU/L, estradiol elevation via aromatase, and lack of assay cross-reactivity for LH come only from a tier-3 clinician guide (HCG / Human Chorionic Gonadotropin for Male Infertility — Male Infertility Guide), not from regulatory labeling.

Limited evidence

Mouse teratogenicity data may not translate directly to humans

The finding of dose-dependent external congenital anomalies is from combined HCG/PMS therapy in mice (Rx Only (chorionic gonadotropin) for injection, for intramuscular use Initial U.S. Approval: 1974 DESCRIPTION: Each 5,000 5,000 Each 10,000 10,000 CLINICAL PHARMACOLOGY: INDICATIONS AND USAGE: CONTRAINDICATIONS: WARNINGS: PRECAUTIONS: General: Carcinogenesis, Mutagenesis, Impairment of Fertility: Nursing Mothers: Pediatric Use: ADVERSE REACTIONS: DOSAGE AND ADMINISTRATION: Reconstitution volume of bacteriostatic water for injection, NOVAREL ® (chorionic gonadotropin) for injection, for intramuscular use Initial U.S. Approval: 1974); it is animal evidence cited in labeling as a caution rather than a demonstrated human effect.

Contested

LH and hCG are increasingly recognized as not fully interchangeable

While most sources describe hCG action as 'virtually identical' to LH (Rx Only (chorionic gonadotropin) for injection, for intramuscular use Initial U.S. Approval: 1974 DESCRIPTION: Each 5,000 5,000 Each 10,000 10,000 CLINICAL PHARMACOLOGY: INDICATIONS AND USAGE: CONTRAINDICATIONS: WARNINGS: PRECAUTIONS: General: Carcinogenesis, Mutagenesis, Impairment of Fertility: Nursing Mothers: Pediatric Use: ADVERSE REACTIONS: DOSAGE AND ADMINISTRATION: Reconstitution volume of bacteriostatic water for injection through DailyMed - CHORIONIC GONADOTROPIN kit), a tier-1 review argues that despite sharing a receptor, LH and hCG have disparate downstream signaling effects and are not as interchangeable as once believed (Luteinizing hormone and human chorionic gonadotropin: origins of difference.).

Using it with other compounds

  • Kisspeptin-10Same downstream effect

    Worth caution

    Kisspeptin-10 works one step further upstream than gonadorelin \it triggers GnRH neurons, which release GnRH, which drives pituitary LH/FSH, which stimulate the gonads. HCG bypasses all of that and directly activates the gonadal LH receptor. Both ultimately raise gonadal sex hormones, so they target the same physiological endpoint by different routes. Stacking is more redundant than synergistic and warrants hormone monitoring.

    Tier 3Largely anecdotal — commonly discussed

    Shares testosterone axis

  • TriptorelinStack with caution

    Research does not support combining these

    These pull the reproductive axis in opposite directions when used as typically dosed. HCG stimulates the gonads to make testosterone, while triptorelin given as a long-acting depot ultimately shuts the axis down to castration-level testosterone (after an initial flare). Combining them means one drug is trying to raise sex hormones while the other drives them toward zero \they largely cancel out and the combination makes little sense.

    Tier 4Theoretical — not established

    Shares testosterone axis

  • GonadorelinComplementary

    Worth caution

    These act at different levels of the same axis: gonadorelin stimulates the pituitary to make endogenous LH/FSH, while HCG bypasses the pituitary and directly stimulates the gonadal LH receptor to drive testosterone/steroidogenesis. In principle they converge on raising sex steroids by distinct routes. However, HCG's direct gonadal drive and negative feedback can blunt the endogenous pituitary output gonadorelin is trying to restore, so pairing them requires understanding the goal (restoring the natural pituitary signal vs. directly firing the testes) and monitoring.

    Tier 4Theoretical — not established

    Shares testosterone axis

  • FOXO4-DRISame downstream effect

    May be complementary

    Both can raise testosterone but by unrelated mechanisms: HCG directly stimulates Leydig-cell steroidogenesis via the LH receptor, whereas FOXO4-DRI is reported to improve testicular function by removing senescent cells that impair it. They converge on the same endpoint and may complement each other.

    Tier 4Theoretical — not established

    Shares testosterone axis

Safety and side effects

Safety and side effects

Contraindications

  • Precocious puberty
  • Prostatic carcinoma or other androgen-dependent neoplasm
  • Prior allergic reaction to HCG
  • HCG may cause fetal harm if given to a pregnant woman.

Serious adverse reactions

When used with human menopausal gonadotropins, principal serious reactions include:

  • Ovarian hyperstimulation syndrome — sudden ovarian enlargement, ascites, pleural effusion
  • Rupture of ovarian cysts with hemoperitoneum
  • Multiple births
  • Arterial thromboembolism

Hypersensitivity

Anaphylaxis and other hypersensitivity reactions (generalized and local, including angioedema) have been reported with urinary-derived products. Reported injection side effects include rash, itching, hives, facial/lip/tongue/throat swelling, and signs of blood clot (pain, swelling).

Other risks and cautions

  • Androgen induction may cause precocious puberty in boys treated for cryptorchidism.
  • Because androgens can cause fluid retention, use with caution in cardiac or renal disease, epilepsy, migraine or asthma.
  • In some men, HCG can raise estradiol to abnormally high levels via aromatase conversion of testosterone (from a single non-regulatory source).
  • Safety/efficacy have not been established under age 4, and recombinant hCG has not been established in children.
  • In an assisted-reproduction trial, adverse events tended to be higher with the 500 mcg recombinant dose than 250 mcg.
  • Herbal/dietary supplements such as blue cohosh, black cohosh, or chasteberry may interact with HCG.

Animal-only signal

Combined HCG/PMS therapy in mice induced dose-dependent external congenital anomalies in offspring — animal evidence cited in labeling as a caution, not a demonstrated human effect.

Reconstitution and handling

Reconstitution and preparation

Urinary-derived chorionic gonadotropin products are extracted from the urine of pregnant women and supplied as a powder for reconstitution before intramuscular administration. When reconstituted with Bacteriostatic Water for Injection preserved with benzyl alcohol 0.9%, the solution should be refrigerated and used within 30 days.

Administration and representative dosing

HCG is given by injection into a muscle or under the skin.

Ovulation induction / assisted reproduction

  • 5,000-10,000 units IM once, one day following the last dose of menotropins, or recombinant hCG (Ovidrel/choriogonadotropin alfa) 250 mcg SC once.
  • Recombinant hCG 250 mcg SC is regarded as equivalent to 10,000 U USP urinary hCG IM for final follicular maturation and luteinization. In a randomized trial of 297 women, mean oocytes retrieved were equivalent across 250 mcg rHCG, 500 mcg rHCG and urinary hCG, though the 500 mcg dose produced significantly more fertilized/cleaved embryos (with a trend toward more adverse events).
  • GnRH agonist can enable ovum maturation with hCG supporting the luteal phase; GnRH-agonist-then-hCG triggering is a newer approach, and hCG is no longer the sole ovulation trigger.

Male hypogonadism

  • 500-1,000 units IM three times weekly for 3 weeks, then twice weekly for 3 weeks, or
  • 4,000 units IM three times weekly for 6-9 months, then 2,000 units three times weekly for 3 months.

Prepubertal cryptorchidism (children ≥4 years)

  • 4,000 units IM three times weekly for 3 weeks, or
  • 5,000 units IM every other day for 4 injections, or
  • 500-1,000 units IM for 15 injections over 6 weeks, or
  • 500 units IM three times weekly for 4-6 weeks.

TRT-adjunct (single non-regulatory source)

For supporting endogenous testosterone, HCG is typically described as given about 3 times per week subcutaneously. Peak increase in testosterone occurs about 72-96 hours after administration. This source also notes HCG is unlikely to raise testosterone if LH is already elevated (>20 IU/L), and that blood LH often does not appear to rise in men on HCG due to limited assay cross-reactivity. These details come from a tier-3 clinician guide rather than regulatory labeling.

Pharmacokinetic notes

After IM administration, serum HCG rises within ~2 hours, peaks by ~6 hours, persists ~36 hours, declines by 48 hours and is undetectable after ~72 hours; roughly 10-12% of the dose is excreted in urine within 24 hours. Distribution is primarily to the testes and ovaries, with small amounts possibly to the proximal tubules of the renal cortex.

Sources

Ordered by evidence quality — the strongest first.

  1. Chorionic Gonadotropin(opens in a new tab)
    Tier 1Web · dailymed.nlm.nih.gov
  2. hCG Triggering in ART: An Evolutionary Concept.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2017
  3. Inherited human chorionic gonadotropin.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2010
  4. Human Chorionic Gonadotropin and Breast Cancer.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2017
  5. Determination of human chorionic gonadotropin.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2013
  6. Immunology of human chorionic gonadotropin (HCG).(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1967

See something wrong or out of date on this page? Report it.