| Chorionic gonadotropin, alpha polypeptide | |||||||
|---|---|---|---|---|---|---|---|
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| Identifiers | |||||||
| Symbol | CGA | ||||||
| Alt. symbols | FSHA, GPHa, GPHA1, HCG, LHA, TSHA | ||||||
| NCBI gene | 1081 | ||||||
| HGNC | 1885 | ||||||
| OMIM | 118850 | ||||||
| RefSeq | NM_000735 | ||||||
| UniProt | P01215 | ||||||
| Other data | |||||||
| Locus | Chr. 6q14-q21 | ||||||
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| chorionic gonadotropin, beta polypeptide | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | CGB | ||||||
| Alt. symbols | CGB3 | ||||||
| NCBI gene | 1082 | ||||||
| HGNC | 1886 | ||||||
| OMIM | 118860 | ||||||
| RefSeq | NM_000737 | ||||||
| UniProt | P01233 | ||||||
| Other data | |||||||
| Locus | Chr. 19q13.3 | ||||||
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Human chorionic gonadotropin (hCG) is ahormone for thematernal recognition of pregnancy produced bytrophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta afterimplantation.[1][2] The presence of hCG is detected in somepregnancy tests (HCG pregnancy strip tests). Somecancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a cancer diagnosis and, if high enough,paraneoplastic syndromes, however, it is unknown whether this production is a contributing cause or an effect ofcarcinogenesis. The pituitary analog of hCG, known asluteinizing hormone (LH), is produced in thepituitary gland of males and females of all ages.[1][3]
Beta-hCG is initially secreted by thesyncytiotrophoblast.[1]
Human chorionic gonadotropin is aglycoprotein composed of 237amino acids with amolecular mass of 36.7kDa, approximately 14.5kDa αhCG and 22.2kDa βhCG.[4]
It isheterodimeric, with an α (alpha)subunit identical to that ofluteinizing hormone (LH),follicle-stimulating hormone (FSH),thyroid-stimulating hormone (TSH), and a β (beta) subunit that is unique to hCG.
The two subunits create a smallhydrophobic core surrounded by a high surface area-to-volume ratio: 2.8 times that of a sphere. The vast majority of the outer amino acids arehydrophilic.[7]
beta-hCG is mostly similar tobeta-LH, with the exception of a Carboxy Terminus Peptide (beta-CTP) containing four glycosylated serine residues that is responsible for hCG's longer half-life.[8]
Human chorionic gonadotropin interacts with theLHCG receptor of the ovary and promotes the maintenance of thecorpus luteum for thematernal recognition of pregnancy at the beginning ofpregnancy. This allows the corpus luteum tosecrete the hormoneprogesterone during the first trimester. Progesterone enriches theuterus with a thicklining ofblood vessels andcapillaries so that it can sustain the growingfetus.[9]
It has been hypothesized that hCG may be a placental link for the development of local maternalimmunotolerance.[10] For example, hCG-treated endometrial cells induce an increase in T cellapoptosis (dissolution ofT cells). These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance, and may facilitate thetrophoblast invasion, which is known to expedite fetal development in the endometrium.[11] It has also been suggested that hCG levels are linked to the severity ofmorning sickness orhyperemesis gravidarum in pregnant women.[12]
Because of its similarity to LH, hCG can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes. As the most abundant biological source is in women who are presently pregnant, some organizations collect urine from pregnant women to extract hCG for use in fertility treatment.[citation needed]
Human chorionic gonadotropin also plays a role in cellular differentiation/proliferation and may activate apoptosis.[citation needed]
Naturally, it is produced in the human placenta by thesyncytiotrophoblast.[1]
Like any othergonadotropins, it can be extracted from the urine of pregnant women or produced from cultures of genetically modified cells usingrecombinant DNA technology.
InPubergen, Pregnyl, Follutein, Profasi,Choragon andNovarel, it is extracted from the urine of pregnant women. InOvidrel, it is produced withrecombinant DNA technology.[13]
Three major forms of hCG are produced by humans, with each having distinct physiological roles. These include regular hCG, hyperglycosylated hCG, and the free beta-subunit of hCG. Degradation products of hCG have also been detected, including nicked hCG, hCG missing the C-terminal peptide from the beta-subunit, and free alpha-subunit, which has no known biological function. Some hCG is also made by thepituitary gland with a pattern ofglycosylation that differs from placental forms of hCG.[1]
Regular hCG is the main form of hCG associated with the majority of pregnancy and in non-invasive molar pregnancies. This is produced in thetrophoblast cells of the placental tissue. Hyperglycosylated hCG is the main form of hCG during the implantation phase of pregnancy, with invasive molar pregnancies, and withchoriocarcinoma.[14]
Gonadotropin preparations of hCG can be produced for pharmaceutical use fromanimal orsynthetic sources.[citation needed]
Blood orurine tests measure hCG. These can bepregnancy tests. hCG-positive can indicate an implantedblastocyst andmammalian embryogenesis or can be detected for a short time following childbirth or pregnancy loss. Tests can be done to diagnose and monitorgerm cell tumors andgestational trophoblastic diseases.
Concentrations are commonly reported in thousandth international units per milliliter (mIU/mL). The international unit of hCG was originally established in 1938 and has been redefined in 1964 and in 1980.[15] At the present time, 1 international unit is equal to approximately 2.35×10−12 moles,[16] or about 6×10−8 grams.[17]
It is also possible to test for hCG to have an approximation of the gestational age.[18]
Most tests employ a monoclonal antibody, which is specific to theβ-subunit of hCG (β-hCG). This procedure is employed to ensure that tests do not makefalse positives by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, whereas the presence of hCG almost always indicates pregnancy.)[citation needed]
Many hCG immunoassays are based on thesandwich principle, which uses antibodies to hCG labeled with an enzyme or a conventional or luminescent dye.Pregnancy urine dipstick tests are based on thelateral flow technique.
The hCG levels grow exponentially after conception and implantation.[21] hCG levels typically peak around weeks 8-11 of pregnancy and are generally higher in the first trimester compared to the second trimester.
The following is a list of serum hCG levels:
LMP is thelast menstrual period dated from the first day of the last menstrual period
| weeks since LMP | mIU/mL |
|---|---|
| 3 | 5 – 50 |
| 4 | 5 – 428 |
| 5 | 18 – 7,340 |
| 6 | 1,080 – 56,500 |
| 7 – 8 | 7,650 – 229,000 |
| 9 – 12 | 25,700 – 288,000 |
| 13 – 16 | 13,300 – 254,000 |
| 17 – 24 | 4,060 – 165,400 |
| 25 – 40 | 3,640 – 117,000 |
| Non-pregnant females | <5.0 |
| Postmenopausal females | <9.5 |
If a pregnant woman has serum hCG levels that are higher than expected, they may be experiencing amultiple pregnancy or an abnormal uterine growth. Falling hCG levels may indicate the possibility of a miscarriage. hCG levels which are rising at a slower rate than expected may indicate anectopic pregnancy.[22]
The ability to quantitate the βhCG level is useful in monitoringgerm cell andtrophoblastic tumors, follow-up care aftermiscarriage, and diagnosis of and follow-up care after treatment ofectopic pregnancy. The lack of a visible fetus on vaginalultrasound after βhCG levels reach 1500 mIU/mL is strongly indicative of an ectopic pregnancy.[23] Still, even an hCG over 2000 IU/L does not necessarily exclude the presence of a viable intrauterine pregnancy in such cases.[24]
As pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hCG between 6 and 12 days after ovulation.[25] It must be taken into account, however, that total hCG levels may vary in a very wide range within the first 4 weeks of gestation, leading to false results during this period.[26] A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.[24]
Gestational trophoblastic disease likehydatidiform moles ("molar pregnancy") or choriocarcinoma may produce high levels of βhCG due to the presence ofsyncytiotrophoblasts, part of the villi that make up the placenta, and despite the absence of an embryo. This, as well as several other conditions, can lead to elevated hCG readings in the absence of pregnancy.[citation needed]
hCG levels are also a component of thetriple test, a screening test for certain fetal chromosomal abnormalities/birth defects. High hCG levels in the maternal serum could suggestDown syndrome, potentially due to continued hCG production by the placenta beyond the first trimester.[27]
A study of 32 normal pregnancies came to the result that agestational sac of 1–3 mm was detected at a mean hCG level of 1150 IU/L (range 800–1500), ayolk sac was detected at a mean level of 6000 IU/L (range 4500–7500) andfetal heartbeat was visible at a mean hCG level of 10,000 IU/L (range 8650–12,200).[28]
Human chorionic gonadotropin can be used as atumor marker,[29] as its β subunit is secreted by somecancers includingseminoma,choriocarcinoma,teratoma with elements ofchoriocarcinoma, othergerm cell tumors,hydatidiform mole, andislet cell tumor. For this reason, a positive result in males can be a test fortesticular cancer. The normal range for men is between 0-5 mIU/mL. Combined withalpha-fetoprotein, β-HCG is an excellent tumor marker for the monitoring ofgerm cell tumors.[30]
| Clinical data | |
|---|---|
| Trade names | Novarel, Pregnyl |
| AHFS/Drugs.com | Monograph |
| ATC code | |
| Identifiers | |
| CAS Number | |
| DrugBank |
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| ChemSpider |
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| UNII | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.029.679 |
| Chemical and physical data | |
| Formula | C1105H1770N318O336S26 |
| Molar mass | 25719.77 g·mol−1 |
 N Y (what is this?) | |
Human chorionic gonadotropin injection is extensively used forfinal maturation induction in lieu ofluteinizing hormone. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of HCG. Asovulation will happen between 38 and 40 hours after a single HCG injection,[31] procedures can be scheduled to take advantage of this time sequence,[32][unreliable medical source?] such asintrauterine insemination or sexual intercourse. Also, patients that undergoIVF, in general, receive HCG to trigger the ovulation process, but have anoocyte retrieval performed at about 34 to 36 hours after injection, a few hours before the eggs actually would be released from the ovary.[citation needed]
As hCG supports thecorpus luteum, administration of hCG is used in certain circumstances to enhance the production ofprogesterone.
Several vaccines against human chorionic gonadotropin (hCG) for the prevention of pregnancy are currently in clinical trials.[33]
In males, hCG injections are used to stimulate theLeydig cells to synthesizetestosterone.[34] The intratesticular testosterone is necessary forspermatogenesis from thesertoli cells. Typical medical uses for hCG in males include treating certain types ofhypogonadism (either as monotherapy, or, more commonly, in combination withexogenous testosterone), as well as to either treat or prevent infertility, for example, during testosterone replacement therapy hCG is often used to restore or maintain fertility and prevent testicular atrophy.[35][36]
In the case of female patients who want to be treated with HCG Pubergen, Pregnyl:[citation needed]a) Since infertile female patients who undergo medically assisted reproduction (especially those who needin vitro fertilization), are known to often be suffering from tubal abnormalities, after a treatment with this drug they might experience many moreectopic pregnancies. This is why early ultrasound confirmation at the beginning of a pregnancy (to see whether the pregnancy is intrauterine or not) is crucial. Pregnancies that have occurred after a treatment with this drug have a higher risk ofmultiple pregnancy. Female patients who have thrombosis, severe obesity, or thrombophilia should not be prescribed this medicine as they have a higher risk of arterial or venous thromboembolic events after or during a treatment with HCG Pubergen, Pregnyl. b)Female patients who have been treated with this medicine are usually more prone to pregnancy losses.[citation needed]
In the case of male patients: A prolonged treatment with HCG Pubergen, Pregnyl is known to regularly lead to increased production of androgen. Therefore: Patients who have overt or latent cardiac failure, hypertension, renal dysfunction, migraines, or epilepsy might not be allowed to start using this medicine or may require a lower dose of HCG Pubergen, Pregnyl. This drug should be used with extreme caution in the treatment ofprepubescent teenagers in order to reduce the risk of precocious sexual development or premature epiphyseal closure. This type of patients' skeletal maturation should be closely and regularly monitored.[citation needed]
Both male and female patients who have the following medical conditions must not start a treatment with HCG Pubergen, Pregnyl: (1) Hypersensitivity to this drug or to any of its main ingredients. (2) Known or possible androgen-dependent tumors for example male breast carcinoma or prostatic carcinoma.
HCG is included in some sports'banned substances lists.
When exogenous AAS (Anabolic Androgenic Steroids) are put into the male body, natural negative-feedback loops cause the body to shut down its own production oftestosterone via shutdown of the hypothalamic-pituitary-gonadal axis (HPGA). This causes testicular atrophy, among other things. HCG is commonly used during and after steroid cycles to maintain and restore testicular size as well as normal testosterone production.[37]
High levels of AASs, that mimic the body's natural testosterone, trigger thehypothalamus to shut down its production ofgonadotropin-releasing hormone (GnRH) from the hypothalamus. Without GnRH, thepituitary gland stops releasingluteinizing hormone (LH). LH normally travels from the pituitary via the blood stream to the testes, where it triggers the production and release of testosterone. Without LH, the testes shut down their production of testosterone.[38] In males, HCG helps restore and maintain testosterone production in the testes by mimicking LH and triggering the production and release of testosterone.[citation needed]
Professional athletes who have tested positive for HCG have been temporarily banned from their sport, including a 50-game ban fromMLB forManny Ramirez in 2009[39] and a 4-game ban from theNFL forBrian Cushing for a positive urine test for HCG.[40]Mixed Martial Arts fighterDennis Siver was fined $19,800 and suspended 9 months for being tested positive after his bout atUFC 168.[41] Jurickson Profar tested positive for the substance and was suspended for 80-games on 3/31/2025.[42]
British endocrinologistAlbert T. W. Simeons proposed HCG as an adjunct to an ultra-low-calorie weight-loss diet (fewer than 500 calories).[43] Simeons, while studying pregnant women in India on a calorie-deficient diet, and obese boys with pituitary issues (Frölich's syndrome) treated with low-dose HCG, observed that both lost fat rather than lean (muscle) tissue.[43] He reasoned that HCG must be programming thehypothalamus to do this in the former cases in order to protect the developing fetus by promoting mobilization and consumption ofabnormal,excessiveadipose deposits. Simeons in 1954 published a book entitledPounds and Inches, designed to combat obesity. Simeons, practicing at Salvator Mundi International Hospital in Rome, Italy, recommended low-dose daily HCG injections (125 IU) in combination with a customized ultra-low-calorie (500 cal/day, high-protein, low-carbohydrate/fat) diet, which was supposed to result in a loss of adipose tissue without loss of lean tissue.[43]
Other researchers did not find the same results when attempting experiments to confirm Simeons' conclusions, and in 1976 in response to complaints the FDA required Simeons and others to include the following disclaimer on all advertisements:[44]
These weight reduction treatments include the injection of HCG, a drug which has not been approved by the Food and Drug Administration as safe and effective in the treatment of obesity or weight control. There is no substantial evidence that HCG 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-restrictive diets.
— 1976 FDA-mandated disclaimer for HCG diet advertisements
There was a resurgence of interest in the "HCG diet" following promotion byKevin Trudeau, who was banned from making HCG diet weight-loss claims by the U.S.Federal Trade Commission in 2008, and eventually jailed over such claims.[45][46]
A 1976 study in theAmerican Journal of Clinical Nutrition[47] concluded that HCG is not more effective as a weight-loss aid than dietary restriction alone.[48]
A 1995 meta analysis found that studies supporting HCG for weight loss were of poor methodological quality and concluded that "there is no scientific evidence that HCG is effective in the treatment of obesity; it does not bring about weight-loss or fat-redistribution, nor does it reduce hunger or induce a feeling of well-being".[49]
On November 15, 2016, theAmerican Medical Association (AMA) passed policy that "The use of human chorionic gonadotropin (HCG) for weight loss is inappropriate."[50]
There is no scientific evidence that HCG is effective in the treatment of obesity. The meta-analysis found insufficient evidence supporting the claims that HCG is effective in altering fat-distribution, hunger reduction, or in inducing a feeling of well-being. The authors stated "…the use of HCG should be regarded as an inappropriate therapy for weight reduction…" In the authors opinion, "Pharmacists and physicians should be alert on the use of HCG for Simeons therapy. The results of this meta-analysis support a firm standpoint against this improper indication. Restraints on physicians practicing this therapy can be based on our findings."
According to the American Society of Bariatric Physicians, no new clinical trials have been published since the definitive 1995 meta-analysis.[51]
The scientific consensus is that any weight loss reported by individuals on an "HCG diet" may be attributed entirely to the fact that such diets prescribe calorie intake of between 500 and 1,000 calories per day, substantially below recommended levels for an adult, to the point that this may risk health effects associated with malnutrition.[52]
Controversy about, and shortages[53] of, injected HCG for weight loss have led to substantial Internet promotion of "homeopathic HCG" for weight control. The ingredients in these products are often obscure, but if prepared from true HCG via homeopathic dilution, they contain either no HCG at all or only trace amounts. Moreover, it is highly unlikely that oral HCG is bioavailable due to the fact that digestive protease enzymes and hepatic metabolism renders peptide-based molecules (such as insulin and human growth hormone) biologically inert. HCG can likely only enter the bloodstream through injection.[citation needed]
The United StatesFood and Drug Administration has stated that over-the-counter products containing HCG are fraudulent and ineffective for weight loss. They are also not protected as homeopathic drugs and have been deemed illegal substances.[54] HCG is classified as a prescription drug in the United States and it has not been approved for over-the-counter sales by the FDA as a weight loss product or for any other purposes, and therefore neither HCG in its pure form nor any preparations containing HCG may be sold legally in the country except by prescription.[55] In December 2011, FDA and FTC started to take actions to pull unapproved HCG products from the market.[55] In the aftermath, some suppliers started to switch to "hormone-free" versions of their weight loss products, where the hormone is replaced with an unproven mixture of free amino acids[56] or whereradionics is used to transfer the "energy" to the final product.[citation needed]
As of December 6, 2011[update], the United StatesFood and Drug Administration has prohibited the sale ofhomeopathic andover-the-counter hCGdiet products and declared themfraudelent and banned.[55][57][58]
Catholic Bishops in Kenya[59] are among those who have spread aconspiracy theory[60] asserting that HCG forms part of a covert sterilization program, forcing denials from the Kenyan government.[59]
In order to induce a stronger immune response, some versions of human chorionic gonadotropin-based anti-fertility vaccines were designed asconjugates of the β subunit of HCG covalently linked totetanus toxoid.[33][61] It was alleged that a non-conjugatedtetanus vaccine used in developing countries was laced with a human chorionic gonadotropin-based anti-fertility drug and was distributed as a means ofmass sterilization.[62] This charge has been vigorously denied by theWorld Health Organization (WHO) andUNICEF.[63] Others have argued that an hCG-laced vaccine could not possibly be used for sterilization, since the effects of the anti-fertility vaccines are reversible (requiringbooster doses to maintain infertility) and a non-conjugated vaccine is likely to be ineffective.[64] Finally, independent testing of the tetanus vaccine by Kenya's health authorities revealed no traces of the human chorionic gonadotropin hormone.[65]
P01215[25-116]
P0DN86[21-165]; Two specific hCGb proteins that differ by three amino acids in positions 2,4 and 117 have been described: type 1 (CGB7) and type 2 (CGB3, CGB5, CGB8).
FTC v. Trudeau (7th Cir., 2009) 579 F.3d 754 remanded (N.D.Ill., 2010) 708 F.Supp.2d 711, affirmed (7th Cir. 2011) 662 F.3d 947, certiorari denied (Oct. 9, 2012) _U.S._, 133 S.Ct. 426, 184 L.Ed.2d 257; and a ten-year prison sentence for violating a court order,U.S. v. Trudeau (N.D.Ill., Jan. 29, 2014) 2014 u.s.dist. LEXIS 10717, 2014 WL 321373.
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