Human chorionic gonadotropin
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Human chorionic gonadotropin (hCG) is a
Various endogenous forms of hCG exist. The measurement of these diverse forms is used in the diagnosis of pregnancy and a variety of disease states.[1] Preparations of hCG from various sources have also been used therapeutically, by both medicine and quackery. As of December 6, 2011[update], the United States Food and Drug Administration has prohibited the sale of "homeopathic" and over-the-counter hCG diet products and declared them fraudulent and illegal.[4][5][6]
Beta-hCG is initially secreted by the syncytiotrophoblast.[citation needed]
Structure
Human chorionic gonadotropin is a
It is
- The
- The β-subunit of hCG gonadotropin (beta-hCG) contains 145 amino acids, encoded by six highly homologous
The two subunits create a small
beta-hCG is mostly similar to
Function
Human chorionic gonadotropin interacts with the
It has been hypothesized that hCG may be a placental link for the development of local maternal immunotolerance.[13] 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.[14] It has also been suggested that hCG levels are linked to the severity of morning sickness or hyperemesis gravidarum in pregnant women.[15]
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]
Production
Naturally, it is produced in the human placenta by the syncytiotrophoblast.[citation needed]
Like any other
In
hCG forms
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.[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 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.[17]
Gonadotropin preparations of hCG can be produced for pharmaceutical use from animal or synthetic sources.[citation needed]
Testing
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.[18] At the present time, 1 international unit is equal to approximately 2.35×10−12 moles,[19] or about 6×10−8 grams.[20]
It is also possible to test for hCG to have an approximation of the gestational age.[21]
Methodology
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.)[citation needed]
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 specific gravityless 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[22] that can detect βhCG levels as low as 5 mIU/mL and allows quantification of the βhCG concentration.
Reference levels in normal pregnancy
The hCG levels grow exponentially after conception and implantation.[24] 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
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 a
Interpretation
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.[26] Still, even an hCG over 2000 IU/L does not necessarily exclude the presence of a viable intrauterine pregnancy in such cases.[27]
As pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hCG between 6 and 12 days after ovulation.[28] 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.[29] A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.[27]
Associations with pathologies
Gestational trophoblastic disease like
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.[30]
A study of 32 normal pregnancies came to the result that a
Uses
Tumor marker
Human chorionic gonadotropin can be used as a
Fertility
Clinical data | |
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ECHA InfoCard | 100.029.679 |
Chemical and physical data | |
Formula | C1105H1770N318O336S26 |
Molar mass | 25719.77 g·mol−1 |
(what is this?) |
Human chorionic gonadotropin injection is extensively used for
As hCG supports the corpus luteum, administration of HCG is used in certain circumstances to enhance the production of progesterone.
In the male, hCG injections are used to stimulate the
Several vaccines against human chorionic gonadotropin (hCG) for the prevention of pregnancy are currently in clinical trials.[38]
HCG Pubergen, Pregnyl warnings
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 need
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
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.
Anabolic steroid adjunct
In the world of performance-enhancing drugs, HCG is increasingly used in combination with various
When exogenous AAS are put into the male body, natural negative-feedback loops cause the body to shut down its own production of
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.[40] In males, HCG helps restore and maintain testosterone production in the testes by mimicking LH and triggering the production and release of testosterone.
Professional athletes who have tested positive for HCG have been temporarily banned from their sport, including a 50-game ban from
HCG diet
British endocrinologist
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:[45]
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.[46][47]
A 1976 study in the
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".[50]
On November 15, 2016, the American Medical Association (AMA) passed policy that "The use of human chorionic gonadotropin (HCG) for weight loss is inappropriate."[51]
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.[52]
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.[53]
Homeopathic HCG for weight control
Controversy about, and shortages[54] 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 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.[55] 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.[4] In December 2011, FDA and FTC started to take actions to pull unapproved HCG products from the market.[4] 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 where radionics is used to transfer the "energy" to the final product.[citation needed]
Tetanus vaccine conspiracy theory
Catholic Bishops in Kenya[57] are among those who have spread a conspiracy theory[58] asserting that HCG forms part of a covert sterilization program, forcing denials from the Kenyan government.[57]
In order to induce a stronger immune response, some versions of human chorionic gonadotropin-based anti-fertility vaccines were designed as
See also
- Equine chorionic gonadotropin
- Gonadotropin preparations
- Human placental lactogen
- screening test in pregnancy
- The Weight-Loss Cure "They" Don't Want You to Know About - Kevin Trudeau's book
References
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- ^ "FDA, FTC act to remove 'homeopathic' HCG weight loss products from the market" (PDF) (Press release). FDA. 6 December 2011. Retrieved 5 January 2021.
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- ^ "Choriogonadotropin subunit beta 3 - Homo sapiens (Human)". UniProt accession number P01233. UniProt Consortium.
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).
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- ^ "Guideline To HCG Levels During Pregnancy". American Pregnancy Association. 22 August 2017.
- ^ "hCG levels". www.pregnancybirthbaby.org.au. 21 December 2022. Retrieved 17 January 2023.
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- ^ HCG Injection After Ovulation Induction With Clomiphene Citrate at Medscape. By Peter Kovacs. Posted: 04/23/2004
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- ^ Schmidt MS (May 8, 2009). "Manny Ramirez Is Banned for 50 Games". The New York Times.
- ^ McClain J (2010-05-12). "Cushing suspended for performance-enhancing drugs". Houston Texans Football. Houston Chronicle. Retrieved 2010-10-23.
- ^ Holland JS (April 24, 2014). "Dennis Siver fined, suspended nine months for positive drug test following UFC 168". MMAMania.com.
- ^ ISBN 978-0-615-42755-3.
- ^ 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.
- ^ "Kevin Trudeau Banned from Infomercials For Three Years, Ordered to Pay More Than $5 Million for False Claims About Weight-Loss Book". Federal Trade Commission. 6 October 2008.
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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- ^ "Chorionic Gonadotropin (Human) Injection Shortage". Bulletin. American Society of Health-System Pharmacists. 2010-10-13. Archived from the original on 2011-09-19. Retrieved 2010-10-23.
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- ^ "Hormone-Free HCG Drops are Quickly Replacing Homeopathic Counterparts". San Francisco Chronicle. March 9, 2012.
- ^ a b Ohlheiser A. "The tense standoff between Catholic bishops and the Kenyan government over tetanus vaccines". Washington Post. Retrieved 2020-06-04.
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External links
- Chorionic+Gonadotropin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "History of pregnancy test". U.S. National Institutes of Health.