human chorionic gonadotropin

Human 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 βhCG.{{cite journal | vauthors = Canfield RE, O'Connor JF, Birken S, Krichevsky A, Wilcox AJ | title = Development of an assay for a biomarker of pregnancy and early fetal loss | journal = Environmental Health Perspectives | volume = 74 | pages = 57–66 | date = October 1987 | pmid = 3319556 | pmc = 1474496 | doi = 10.1289/ehp.877457 | bibcode = 1987EnvHP..74...57C }}

It is heterodimeric, with an α (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and a β (beta) subunit that is unique to hCG.

• The α (alpha) subunit is 92 amino acids long.{{cite web | url = https://www.uniprot.org/uniprot/P01215 | title = Glycoprotein hormones alpha chain precursor - Homo sapiens (Human) | publisher = UniProt Consortium | work = UniProt accession number P01215 | quote = P01215[25-116] }}
• The β-subunit of hCG gonadotropin (beta-hCG) contains 145 amino acids, encoded by six highly homologous genes that are arranged in tandem and inverted pairs on chromosome 19q13.3 - CGB (1, 2, 3, 5, 7, 8). It is known that CGB7 has a sequence slightly different from that of the others.{{cite web | url = https://www.uniprot.org/uniprot/P0DN86 | title = Choriogonadotropin subunit beta 3 - Homo sapiens (Human) | publisher = UniProt Consortium | work = UniProt accession number P01233 | quote = 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).}}

The two subunits create a small hydrophobic 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 are hydrophilic.{{PDB|1HRP}}; {{cite journal | vauthors = Lapthorn AJ, Harris DC, Littlejohn A, Lustbader JW, Canfield RE, Machin KJ, Morgan FJ, Isaacs NW | title = Crystal structure of human chorionic gonadotropin | journal = Nature | volume = 369 | issue = 6480 | pages = 455–461 | date = June 1994 | pmid = 8202136 | doi = 10.1038/369455a0 | s2cid = 4263358 | bibcode = 1994Natur.369..455L }}

beta-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-life.{{cite journal | vauthors = Furuhashi M, Shikone T, Fares FA, Sugahara T, Hsueh AJ, Boime I | title = Fusing the carboxy-terminal peptide of the chorionic gonadotropin (CG) beta-subunit to the common alpha-subunit: retention of O-linked glycosylation and enhanced in vivo bioactivity of chimeric human CG | journal = Molecular Endocrinology | volume = 9 | issue = 1 | pages = 54–63 | date = January 1995 | pmid = 7539107 | doi = 10.1210/mend.9.1.7539107 | doi-access = free }}

Human chorionic gonadotropin interacts with the LHCG receptor of the ovary and promotes the maintenance of the corpus luteum for the maternal recognition of pregnancy at the beginning of pregnancy. This allows the corpus luteum to secrete the hormone progesterone during the first trimester. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus.{{Cite web|title=Stages of Fetal Development - First Trimester {{!}} Department of Health {{!}} State of Louisiana|url=https://ldh.la.gov/index.cfm/page/986|access-date=2021-02-16|website=ldh.la.gov}}

It has been hypothesized that hCG may be a placental link for the development of local maternal immunotolerance.{{cite journal | vauthors = Schumacher A, Heinze K, Witte J, Poloski E, Linzke N, Woidacki K, Zenclussen AC | title = Human chorionic gonadotropin as a central regulator of pregnancy immune tolerance | journal = Journal of Immunology | volume = 190 | issue = 6 | pages = 2650–2658 | date = March 2013 | pmid = 23396945 | doi = 10.4049/jimmunol.1202698 | doi-access = free }} For example, hCG-treated endometrial cells induce an increase in T cell apoptosis (dissolution of T cells). These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance, and may facilitate the trophoblast invasion, which is known to expedite fetal development in the endometrium.{{cite journal | vauthors = Kayisli UA, Selam B, Guzeloglu-Kayisli O, Demir R, Arici A | title = Human chorionic gonadotropin contributes to maternal immunotolerance and endometrial apoptosis by regulating Fas-Fas ligand system | journal = Journal of Immunology | volume = 171 | issue = 5 | pages = 2305–2313 | date = September 2003 | pmid = 12928375 | doi = 10.4049/jimmunol.171.5.2305 | doi-access = free }} It has also been suggested that hCG levels are linked to the severity of morning sickness or hyperemesis gravidarum in pregnant women.{{cite journal | vauthors = Askling J, Erlandsson G, Kaijser M, Akre O, Ekbom A | title = Sickness in pregnancy and sex of child | journal = Lancet | volume = 354 | issue = 9195 | pages = 2053 | date = December 1999 | pmid = 10636378 | doi = 10.1016/S0140-6736(99)04239-7 | s2cid = 43817834 }}

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.{{cn|date=September 2023}}

Human chorionic gonadotropin also plays a role in cellular differentiation/proliferation and may activate apoptosis.{{cn|date=September 2023}}

Naturally, it is produced in the human placenta by the syncytiotrophoblast.

Like any other gonadotropins, it can be extracted from the urine of pregnant women or produced from cultures of genetically modified cells using recombinant DNA technology.

In Pubergen, Pregnyl, Follutein, Profasi, Choragon and Novarel, it is extracted from the urine of pregnant women. In Ovidrel, it is produced with recombinant DNA technology.{{cite journal | title = Gonadotropin preparations: past, present, and future perspectives | journal = Fertility and Sterility | volume = 90 | issue = 5 Suppl | pages = S13–S20 | date = November 2008 | pmid = 19007609 | doi = 10.1016/j.fertnstert.2008.08.031 | vauthors = ((Practice Committee Of American Society For Reproductive Medicine, Birmingham, Alabama)) | doi-access = free }}

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 the pituitary gland with a pattern of glycosylation that differs from placental forms of hCG.

Regular hCG is the main form of hCG associated with the majority of pregnancy and in non-invasive molar pregnancies. This is produced in the trophoblast cells of the placental tissue. Hyperglycosylated hCG is the main form of hCG during the implantation phase of pregnancy, with invasive molar pregnancies, and with choriocarcinoma.{{cite journal | vauthors = Cole LA | title = Biological functions of hCG and hCG-related molecules | journal = Reproductive Biology and Endocrinology | volume = 8 | pages = 102 | date = August 2010 | pmid = 20735820 | pmc = 2936313 | doi = 10.1186/1477-7827-8-102 | doi-access = free }}

Gonadotropin preparations of hCG can be produced for pharmaceutical use from animal or synthetic sources.{{cn|date=September 2023}}

File:Pregnancy test series starting to show positive.jpg

Blood or urine tests measure hCG. These can be pregnancy tests. hCG-positive can indicate an implanted blastocyst and mammalian embryogenesis or can be detected for a short time following childbirth or pregnancy loss. Tests can be done to diagnose and monitor germ cell tumors and gestational 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.{{cite journal | vauthors = Peters AJ | title = The Diagnosis of Pregnancy | veditors = von Dadelszen P | journal = Global Library of Women's Medicine | date = May 2008 | doi = 10.3843/GLOWM.10093 |url=http://www.glowm.com/index.html?p=glowm.cml/section_view&articleid=93}} At the present time, 1 international unit is equal to approximately 2.35×10⁻¹² moles,{{cite web|url=http://www.nibsc.ac.uk/documents/ifu/99-688.pdf|title=WHO Reference Reagent Human Chorionic Gonadotrophin (Purified) NIBSC code: 99/688 Instructions for use (Version 3.0, Dated 05/11/2007)|url-status=dead|archive-url=https://web.archive.org/web/20121203215926/http://www.nibsc.ac.uk/documents/ifu/99-688.pdf|archive-date=2012-12-03}} or about 6×10⁻⁸ grams.{{cite journal | vauthors = Canfield RE, Ross GT | title = A new reference preparation of human chorionic gonadotrophin and its subunits | journal = Bulletin of the World Health Organization | volume = 54 | issue = 4 | pages = 463–472 | year = 1976 | pmid = 1088359 | pmc = 2366462 }}

It is also possible to test for hCG to have an approximation of the gestational age.{{cite book| vauthors = Wallach J |title=Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|year=2014|isbn=978-1-4511-9176-9|edition=10th|location=Philadelphia}}

Most tests employ a monoclonal antibody, which is specific to the β-subunit of hCG (β-hCG). This procedure is employed to ensure that tests do not make false 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.){{cn|date=September 2023}}

Many hCG immunoassays are based on the sandwich principle, which uses antibodies to hCG labeled with an enzyme or a conventional or luminescent dye.

Pregnancy urine dipstick tests are based on the lateral flow technique.

• The urine test may be a chromatographic immunoassay or any of several other test formats, home-, physician's office-, or laboratory-based.{{cite book | vauthors = McPherson RA, Pincus MR |title=Henry's Clinical Diagnosis and Management by Laboratory Methods |publisher=Saunders |location=Philadelphia |year=2006 |isbn=978-1-4160-0287-1 |edition=21st}}{{Page needed|date=December 2011}} Published detection thresholds range from 20 to 100 mIU/mL, depending on the brand of test.{{cite web| vauthors = Waddell RS | year=2006| title=FertilityPlus.org| work=Home Pregnancy Test hCG Levels and FAQ| url=http://www.fertilityplus.org/faq/hpt.html| access-date=2006-06-17| url-status=dead| archive-url=https://web.archive.org/web/20060615212054/http://www.fertilityplus.org/faq/hpt.html| archive-date=2006-06-15}} Early in pregnancy, more accurate results may be obtained by using the first urine of the morning (when urine is most concentrated). When the urine is dilute (specific gravity less than 1.015), the hCG concentration may not be representative of the blood concentration, and the test may be falsely negative.
• The serum test, using 2-4 mL of venous blood, is typically a chemiluminescent or fluorimetric immunoassay that can detect βhCG levels as low as 5 mIU/mL and allows quantification of the βhCG concentration.

The hCG levels grow exponentially after conception and implantation.{{cite web |date=22 August 2017 |title=Guideline To HCG Levels During Pregnancy |url=http://americanpregnancy.org/while-pregnant/hcg-levels/ |publisher=American Pregnancy Association}} 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 the last menstrual period dated from the first day of the last menstrual period

If a pregnant woman has serum hCG levels that are higher than expected, they may be experiencing a multiple 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 an ectopic pregnancy.{{cite web |title=hCG levels |url=https://www.pregnancybirthbaby.org.au/hcg-levels |website=www.pregnancybirthbaby.org.au |access-date=17 January 2023 |language=en-AU |date=21 December 2022}}

The ability to quantitate the βhCG level is useful in monitoring germ cell and trophoblastic tumors, follow-up care after miscarriage, and diagnosis of and follow-up care after treatment of ectopic pregnancy. The lack of a visible fetus on vaginal ultrasound after βhCG levels reach 1500 mIU/mL is strongly indicative of an ectopic pregnancy.{{cite web | vauthors = Tualndi T | date = February 2022 | veditors = Barbieri RL, Chakrabarti A | title=Ectopic (tubal) pregnancy |url=http://www.uptodate.com/contents/ectopic-tubal-pregnancy-beyond-the-basics|publisher=UpToDate|access-date=1 June 2013}} Still, even an hCG over 2000 IU/L does not necessarily exclude the presence of a viable intrauterine pregnancy in such cases.

As pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hCG between 6 and 12 days after ovulation.{{cite journal | vauthors = Wilcox AJ, Baird DD, Weinberg CR | title = Time of implantation of the conceptus and loss of pregnancy | journal = The New England Journal of Medicine | volume = 340 | issue = 23 | pages = 1796–1799 | date = June 1999 | pmid = 10362823 | doi = 10.1056/NEJM199906103402304 | doi-access = free }} 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.{{cite journal | vauthors = Butler SA, Khanlian SA, Cole LA | title = Detection of early pregnancy forms of human chorionic gonadotropin by home pregnancy test devices | journal = Clinical Chemistry | volume = 47 | issue = 12 | pages = 2131–2136 | date = December 2001 | pmid = 11719477 | doi = 10.1093/clinchem/47.12.2131 | doi-access = free }} A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.{{cite journal | vauthors = Kirk E, Bottomley C, Bourne T | title = Diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location | journal = Human Reproduction Update | volume = 20 | issue = 2 | pages = 250–261 | year = 2013 | pmid = 24101604 | doi = 10.1093/humupd/dmt047 | doi-access = }}

Gestational trophoblastic disease like hydatidiform moles ("molar pregnancy") or choriocarcinoma may produce high levels of βhCG due to the presence of syncytiotrophoblasts, 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.{{cn|date=September 2023}}

hCG levels are also a component of the triple test, a screening test for certain fetal chromosomal abnormalities/birth defects. High hCG levels in the maternal serum could suggest Down syndrome, potentially due to continued hCG production by the placenta beyond the first trimester.{{cite journal | vauthors = Jiang H, Lin Y, He X | title = Association Analysis between Maternal Serum Biomarkers and Fetal Congenital Heart Disease | journal = The Heart Surgery Forum | volume = 26 | issue = 5 | pages = E552–E559 | date = October 2023 | pmid = 37920073 | doi = 10.59958/hsf.6703 | doi-access = free }}

A study of 32 normal pregnancies came to the result that a gestational sac of 1–3 mm was detected at a mean hCG level of 1150 IU/L (range 800–1500), a yolk sac was detected at a mean level of 6000 IU/L (range 4500–7500) and fetal heartbeat was visible at a mean hCG level of 10,000 IU/L (range 8650–12,200).{{cite journal | vauthors = Giacomello F, Magliocchetti P, Loyola G, Giovarruscio M | title = [Serum beta hCG levels and transvaginal echography in the early phases of pregnancy] | language = it | journal = Minerva Ginecologica | volume = 45 | issue = 7–8 | pages = 333–337 | year = 1993 | pmid = 8414139 }}

Human chorionic gonadotropin can be used as a tumor marker,{{cite web|title=Tumor Markers Found in Blood or Urine|url=http://www.cancer.org/treatment/understandingyourdiagnosis/examsandtestdescriptions/tumormarkers/tumor-markers-t-m-blood-urine|publisher=American Cancer Society|access-date=21 January 2014|archive-date=6 March 2014|archive-url=https://web.archive.org/web/20140306072557/http://www.cancer.org/treatment/understandingyourdiagnosis/examsandtestdescriptions/tumormarkers/tumor-markers-t-m-blood-urine|url-status=dead}} as its β subunit is secreted by some cancers including seminoma, choriocarcinoma, teratoma with elements of choriocarcinoma, other germ cell tumors, hydatidiform mole, and islet cell tumor. For this reason, a positive result in males can be a test for testicular cancer. The normal range for men is between 0-5 mIU/mL. Combined with alpha-fetoprotein, β-HCG is an excellent tumor marker for the monitoring of germ cell tumors.{{Cite web|date=2010-06-07|title=Tumor Markers for Testicular Cancer and Extragonadal Germ Cell Tumors in Teenage Boys and Men|url=https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/tumor-markers-testicular-cancer-and-extragonadal-germ-cell-tumors-teenage-boys-and-men|access-date=2021-02-16|website=Cancer.Net|language=en|archive-date=2021-03-03|archive-url=https://web.archive.org/web/20210303091015/https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/tumor-markers-testicular-cancer-and-extragonadal-germ-cell-tumors-teenage-boys-and-men|url-status=dead}}

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Human chorionic gonadotropin injection is extensively used for final maturation induction in lieu of luteinizing hormone. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of HCG. As ovulation will happen between 38 and 40 hours after a single HCG injection,[http://www.medscape.com/viewarticle/473515 HCG Injection After Ovulation Induction With Clomiphene Citrate] at Medscape. By Peter Kovacs. Posted: 04/23/2004 procedures can be scheduled to take advantage of this time sequence,{{cite web | title = Ovulation Induction | url = http://www.ivf.com/ovind.html | work = IVF.com | archive-url = https://web.archive.org/web/20120226141802/http://www.ivf.com/ovind.html | archive-date=2012-02-26 | access-date = 7 March 2010 }}{{Unreliable medical source|date=December 2011}} such as intrauterine insemination or sexual intercourse. Also, patients that undergo IVF, in general, receive HCG to trigger the ovulation process, but have an oocyte retrieval performed at about 34 to 36 hours after injection, a few hours before the eggs actually would be released from the ovary.{{cn|date=September 2023}}

As hCG supports the corpus luteum, administration of hCG is used in certain circumstances to enhance the production of progesterone.

Several vaccines against human chorionic gonadotropin (hCG) for the prevention of pregnancy are currently in clinical trials.{{cite journal | vauthors = Talwar GP, Gupta JC, Rulli SB, Sharma RS, Nand KN, Bandivdekar AH, Atrey N, Singh P | title = Advances in development of a contraceptive vaccine against human chorionic gonadotropin | journal = Expert Opinion on Biological Therapy | volume = 15 | issue = 8 | pages = 1183–1190 | year = 2015 | pmid = 26160491 | doi =

10.1517/14712598.2015.1049943 | hdl = 11336/76410 | s2cid = 10315692 | hdl-access = free }}

In males, hCG injections are used to stimulate the Leydig cells to synthesize testosterone.{{cite journal | vauthors = Riccetti L, De Pascali F, Gilioli L, Potì F, Giva LB, Marino M, Tagliavini S, Trenti T, Fanelli F, Mezzullo M, Pagotto U, Simoni M, Casarini L | title = Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro | journal = Reproductive Biology and Endocrinology | volume = 15 | issue = 1 | pages = 2 | date = January 2017 | pmid = 28056997 | doi = 10.1186/s12958-016-0224-3 | pmc = 5217336 | doi-access = free }} The intratesticular testosterone is necessary for spermatogenesis from the sertoli cells. Typical medical uses for hCG in males include treating certain types of hypogonadism (either as monotherapy, or, more commonly, in combination with exogenous 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.{{cite journal | vauthors = Kim ED, Crosnoe L, Bar-Chama N, Khera M, Lipshultz LI | title = The treatment of hypogonadism in men of reproductive age | journal = Fertility and Sterility | volume = 99 | issue = 3 | pages = 718–724 | date = March 2013 | pmid = 23219010 | doi = 10.1016/j.fertnstert.2012.10.052 | doi-access = free }}{{cite journal | vauthors = Lee JA, Ramasamy R | title = Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men | journal = Translational Andrology and Urology | volume = 7 | issue = Suppl 3 | pages = S348–S352 | date = July 2018 | pmid = 30159241 | doi = 10.21037/tau.2018.04.11 | publisher = AME Publishing Company | doi-access = free | pmc = 6087849 }}

In the case of female patients who want to be treated with HCG Pubergen, Pregnyl:{{cn|date=August 2022}}

a) Since infertile female patients who undergo medically assisted reproduction (especially those who need in vitro fertilization), are known to often be suffering from tubal abnormalities, after a treatment with this drug they might experience many more ectopic 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 of multiple 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.{{cn|date=September 2023}}

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 of prepubescent 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.{{cn|date=September 2023}}

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 of testosterone 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.{{cite news | url = https://www.sfgate.com/sports/article/HCG-helps-steroid-users-restore-testosterone-3162496.php | date = May 8, 2009 | vauthors = Williams L | newspaper = San Francisco Chronicle | title=Manny Ramirez suspended; testosterone ratio exceeded limits; fertility drug reported}}

High levels of AASs, that mimic the body's natural testosterone, trigger the hypothalamus to shut down its production of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Without GnRH, the pituitary gland stops releasing luteinizing 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.{{cite journal | vauthors = van Breda E, Keizer HA, Kuipers H, Wolffenbuttel BH | title = Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study | journal = International Journal of Sports Medicine | volume = 24 | issue = 3 | pages = 195–196 | date = April 2003 | pmid = 12740738 | doi = 10.1055/s-2003-39089 | s2cid = 260166539 }} In males, HCG helps restore and maintain testosterone production in the testes by mimicking LH and triggering the production and release of testosterone.{{cn|date=November 2024}}

Professional athletes who have tested positive for HCG have been temporarily banned from their sport, including a 50-game ban from MLB for Manny Ramirez in 2009{{cite news|url=https://www.nytimes.com/2009/05/08/sports/baseball/08ramirez.html|title=Manny Ramirez Is Banned for 50 Games|date=May 8, 2009| vauthors = Schmidt MS | newspaper=The New York Times}} and a 4-game ban from the NFL for Brian Cushing for a positive urine test for HCG.{{cite web | url = http://www.chron.com/disp/story.mpl/sports/fb/texansfront/6995505.html | title = Cushing suspended for performance-enhancing drugs | vauthors = McClain J | date = 2010-05-12 | work = Houston Texans Football | publisher = Houston Chronicle | access-date = 2010-10-23 }} Mixed Martial Arts fighter Dennis Siver was fined $19,800 and suspended 9 months for being tested positive after his bout at UFC 168.{{cite news|url=http://www.mmamania.com/2014/4/24/5649056/dennis-siver-fined-suspended-nine-months-positive-drug-test-hcg-ufc-168-mma|title=Dennis Siver fined, suspended nine months for positive drug test following UFC 168|date=April 24, 2014| vauthors = Holland JS |newspaper=MMAMania.com}} Jurickson Profar tested positive for the substance and was suspended for 80-games on 3/31/2025.{{cite news|url=https://www.espn.com/mlb/story/_/id/44482019/braves-jurickson-profar-gets-80-game-ban-ped-violation|title=Braves' Jurickson Profar gets 80-game ban for PED violation|date=March 31, 2025| vauthors = Gonzalez A | work=espn.com | access-date=2025-03-31}}

British endocrinologist Albert T. W. Simeons proposed HCG as an adjunct to an ultra-low-calorie weight-loss diet (fewer than 500 calories).{{cite book | vauthors = Simeons AT | title = Pounds & Inches: A New Approach To Obesity | publisher = Popular Publishing | year = 2010 | isbn = 978-0-615-42755-3}} 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. He reasoned that HCG must be programming the hypothalamus to do this in the former cases in order to protect the developing fetus by promoting mobilization and consumption of abnormal, excessive adipose deposits. Simeons in 1954 published a book entitled Pounds 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.

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:In the Matter of Simeon Management Corp. (Fed. Trade Comm'n, 1976) 87 F.T.C. 1184; affirmed by Simeon Management Corp. v. FTC (9th Cir. 1978) 579 F.2d 1137, 49 ALR-Fed 1.

{{quotation|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 by Kevin 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.{{cite web | url = http://www.ftc.gov/opa/2008/10/trudeau.shtm | title = Kevin Trudeau Banned from Infomercials For Three Years, Ordered to Pay More Than $5 Million for False Claims About Weight-Loss Book | date = 6 October 2008 | publisher = Federal Trade Commission | quote = 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. }}{{cite journal | vauthors = Bell CB | title = The Curious Case of Kevin Trudeau, King Catch Me If You Can. | journal = Mississippi Law Journal | date = 2009 | volume = 79 | pages = 1043 | url = http://heinonline.org/HOL/Page?handle=hein.journals/mislj79&div=44&g_sent=1&collection=journals#1053 }}

A 1976 study in the American Journal of Clinical Nutrition{{cite journal | vauthors = Stein MR, Julis RE, Peck CC, Hinshaw W, Sawicki JE, Deller JJ | title = Ineffectiveness of human chorionic gonadotropin in weight reduction: a double-blind study | journal = The American Journal of Clinical Nutrition | volume = 29 | issue = 9 | pages = 940–948 | date = September 1976 | pmid = 786001 | doi = 10.1093/ajcn/29.9.940 | doi-access = free }} concluded that HCG is not more effective as a weight-loss aid than dietary restriction alone.{{cite web | url = http://www.dietscam.org/reports/hcg.shtml | title = HCG Worthless as Weight-Loss Aid | vauthors = Barrett S | work = Diet Scam Watch | publisher = dietscam.org | access-date = 2009-02-03 | archive-date = 2009-01-20 | archive-url = https://web.archive.org/web/20090120183842/http://dietscam.org/reports/hcg.shtml | url-status = dead }}

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".{{cite journal | vauthors = Lijesen GK, Theeuwen I, Assendelft WJ, Van Der Wal G | title = The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis | journal = British Journal of Clinical Pharmacology | volume = 40 | issue = 3 | pages = 237–243 | date = September 1995 | pmid = 8527285 | pmc = 1365103 | doi = 10.1111/j.1365-2125.1995.tb05779.x }}

On November 15, 2016, the American Medical Association (AMA) passed policy that "The use of human chorionic gonadotropin (HCG) for weight loss is inappropriate."{{Cite news|url=https://globenewswire.com/news-release/2016/11/15/890309/10166002/en/Obesity-Medicine-Association-Applauds-American-Medical-Association-s-Decision-to-Adopt-New-Anti-HCG-Policy.html|title=Obesity Medicine Association Applauds American Medical Association's Decision to Adopt New Anti-HCG Policy|date=15 November 2016 | publisher = Obesity Medicine Association | via = GlobeNewswire News Room|language=en-US|access-date=2016-11-16}}

{{quotation|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."| American Society of Bariatric Physicians' commentary on Lijesen et al. (1995)}}

According to the American Society of Bariatric Physicians, no new clinical trials have been published since the definitive 1995 meta-analysis.{{cite web | url = http://www.asbp.org/resources/uploads/files/HCG%20Position%20Statement.pdf | work = American Society of Bariatric Physicians | archive-url = https://web.archive.org/web/20120511014611/http://www.asbp.org/resources/uploads/files/HCG%20Position%20Statement.pdf | archive-date=2012-05-11 | title = Position statement on HCG diet }}

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.{{cite web | url = http://www.mayoclinic.com/health/hcg-diet/AN02091 | title = Does the HCG diet work — and is it safe? | work = Mayo Clinic }}

Controversy about, and shortages{{cite web | url = http://www.ashp.org/DrugShortages/Current/Bulletin.aspx?id=382 | title = Chorionic Gonadotropin (Human) Injection Shortage | date = 2010-10-13 | work = Bulletin | publisher = American Society of Health-System Pharmacists | access-date = 2010-10-23 | archive-date = 2011-09-19 | archive-url = https://web.archive.org/web/20110919004921/http://www.ashp.org/DrugShortages/Current/Bulletin.aspx?id=382 | url-status = dead }} 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.{{cn|date=September 2023}}

The United States Food 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.{{cite web | url = https://www.usatoday.com/yourlife/fitness/weight-loss-challenge/2011-01-24-hcgdiet24_ST_N.htm?loc=interstitialskip | title = HCG weight-loss products are fraudulent, FDA says - USATODAY.com | vauthors = Hellmich N | date = 2011-01-23 | publisher = USA Today | access-date = 2011-02-03 }} 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. In December 2011, FDA and FTC started to take actions to pull unapproved HCG products from the market. 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{{cite news|url=http://www.sfgate.com/cgi-bin/article.cgi?f=/g/a/2012/03/08/prweb9258422.DTL|title=Hormone-Free HCG Drops are Quickly Replacing Homeopathic Counterparts|newspaper=San Francisco Chronicle|date=March 9, 2012}} or where radionics is used to transfer the "energy" to the final product.{{cn|date=September 2023}}

{{As of|2011|12|6|df=US}}, the United States Food and Drug Administration has prohibited the sale of homeopathic and over-the-counter hCG diet products and declared them fraudelent and banned.{{cite news | vauthors = Gever J | date=December 6, 2011 |title=FDA Yanks HCG Weight Loss Agents from Market |url=http://www.medpagetoday.com/ProductAlert/OTC/30042?pfc=101&spc=230 |publisher=MedPage Today |access-date=December 7, 2011}}{{cite web |url=https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm281333.htm |archive-url=https://web.archive.org/web/20111208151744/http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm281333.htm |url-status=dead |archive-date=December 8, 2011 |title=HCG Diet Products Are Illegal |publisher=FDA |date=December 6, 2011}}{{cite press release |title=FDA, FTC act to remove 'homeopathic' HCG weight loss products from the market |publisher=FDA |date=6 December 2011 |url=https://www.ftc.gov/system/files/attachments/press-releases/ftc-charges-hcg-marketer-deceptive-advertising/fda_hcg_products_press_release_12-6-11.pdf |access-date=5 January 2021}}

Catholic Bishops in Kenya{{Cite news | vauthors = Ohlheiser A |title=The tense standoff between Catholic bishops and the Kenyan government over tetanus vaccines |language=en |newspaper=Washington Post |url=https://www.washingtonpost.com/news/worldviews/wp/2014/11/14/the-tense-standoff-between-catholic-bishops-and-the-kenyan-government-over-tetanus-vaccines/ |access-date=2020-06-04}} are among those who have spread a conspiracy theory{{Cite web |title=Is Tetanus Vaccine Spiked with Sterilization Chemicals? |url=https://www.snopes.com/fact-check/tetanus-vaccine-sterilization/ |access-date=2020-06-04 |website=Snopes.com |date=10 November 2014 |language=en-US}} asserting that HCG forms part of a covert sterilization program, forcing denials from the Kenyan government.

In order to induce a stronger immune response, some versions of human chorionic gonadotropin-based anti-fertility vaccines were designed as conjugates of the β subunit of HCG covalently linked to tetanus toxoid.{{cite journal | vauthors = Talwar GP | title = Fertility regulating and immunotherapeutic vaccines reaching human trials stage | journal = Human Reproduction Update | volume = 3 | issue = 4 | pages = 301–310 | year = 1997 | pmid = 9459276 | doi = 10.1093/humupd/3.4.301 | doi-access = free }} It was alleged that a non-conjugated tetanus vaccine used in developing countries was laced with a human chorionic gonadotropin-based anti-fertility drug and was distributed as a means of mass sterilization.{{cite journal | vauthors = | title = Tetanus vaccine may be laced with anti-fertility drug. International / developing countries | journal = Vaccine Weekly | pages = 9–10 | year = 1995 | pmid = 12346214 }} This charge has been vigorously denied by the World Health Organization (WHO) and UNICEF.{{cite web | vauthors = Griffin B | url = https://www.ncronline.org/news/global/who-unicef-deny-kenyan-bishops-claim-they-supplied-sterility-causing-tetanus-vaccines | title = WHO, UNICEF deny Kenyan bishops' claim that they supplied sterility-causing tetanus vaccines | date = 9 March 2015 | work = National Catholic Reporter | access-date = 18 July 2016 | archive-date = 15 August 2016 | archive-url = https://web.archive.org/web/20160815182706/https://www.ncronline.org/news/global/who-unicef-deny-kenyan-bishops-claim-they-supplied-sterility-causing-tetanus-vaccines | url-status = dead }} 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 (requiring booster doses to maintain infertility) and a non-conjugated vaccine is likely to be ineffective.{{cite web | vauthors = Gorski D | url = https://www.sciencebasedmedicine.org/fear-mongering-about-vaccines-as-racist-population-control-in-kenya/ | title = Fear mongering about vaccines as "racist population control" in Kenya | work = Science-Based Medicine | date = 15 November 2014 }} Finally, independent testing of the tetanus vaccine by Kenya's health authorities revealed no traces of the human chorionic gonadotropin hormone.{{cite web | vauthors = Shiundu A | url = http://www.standardmedia.co.ke/health/article/2000140459/health-officials-want-to-punish-doctor-in-tetanus-vaccine-dispute | title = Health officials want to punish doctor in tetanus vaccine dispute | work = Standard Digital | date = 5 November 2014 }}

• Equine chorionic gonadotropin
• Gonadotropin preparations
• Human placental lactogen
• Pregnancy hormones
• Triple test, a screening test in pregnancy
• The Weight-Loss Cure "They" Don't Want You to Know About, a book written by Kevin Trudeau

{{Reflist|33em}}

• {{MeshName|Chorionic+Gonadotropin}}
• {{cite web | url = http://www.history.nih.gov/exhibits/thinblueline/ | title = History of pregnancy test | work = U.S. National Institutes of Health | access-date = 2011-01-10 | archive-date = 2011-01-13 | archive-url = https://web.archive.org/web/20110113130002/http://www.history.nih.gov/exhibits/thinblueline/ | url-status = dead }}

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{{PDB Gallery|geneid=1082}}

{{GnRH and gonadotropins}}

{{Assisted reproductive technology}}

{{Hormones}}

{{GnRH and gonadotropin receptor modulators}}

{{Authority control}}

{{DEFAULTSORT:Human Chorionic Gonadotropin}}

Category:Genes on human chromosome 19

Category:Glycoproteins

Category:Gynaecological endocrinology

Category:Peptide hormones

Category:Drugs developed by Schering-Plough

Category:Drugs developed by Merck & Co.

Category:Drugs developed by Merck

Category:Gonadotropin-releasing hormone and gonadotropins

Category:Hormones of the hypothalamus-pituitary-gonad axis

Category:Sex hormones

Category:Hormones of the placenta

Category:Hormones of the pregnant female

Category:Chemical pathology

Category:Tumor markers

Category:Anti-aging substances

Category:Tests for pregnancy

Category:Human female endocrine system