Human chorionic gonadotropin (hCG)

July 30, 2022
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Structure

  • 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.

Function

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.

Human chorionic gonadotropin also plays a role in cellular differentiation/proliferation and may activate apoptosis.

Production

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.

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. Some of these are medically justified, whereas others are of a quack nature.[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.

  • It is also possible to test for hCG to have an approximation of the gestational age.
    • Wallach, Jacques (2014). Wallach’s Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (10th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-1451191769.

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.)

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.
    • McPherson RA, Pincus MR (2006). Henry’s Clinical Diagnosis and Management by Laboratory Methods (21st ed.). Philadelphia: Saunders. ISBN978-1-4160-0287-1.[page needed] 
  • Published detection thresholds range from 20 to 100 mIU/ml, depending on the brand of test.
  • 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
    • McPherson RA, Pincus MR (2006). Henry’s Clinical Diagnosis and Management by Laboratory Methods (21st ed.). Philadelphia: Saunders. ISBN978-1-4160-0287-1.[page needed] 
  • that can detect βhCG levels as low as 5 mIU/ml and allows quantification of the βhCG concentration.

Reference levels in normal pregnancy[edit]

weeks since LMPmIU/mL
35 – 50
45 – 428
518 – 7,340
61,080 – 56,500
7 – 87,650 – 229,000
9 – 1225,700 – 288,000
13 – 1613,300 – 254,000
17 – 244,060 – 165,400
25 – 403,640 – 117,000
Non-pregnant females<5.0
Postmenopausal females<9.5

Interpretation

  • 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) despite the absence of an embryo. This, as well as several other conditions, can lead to elevated hCG readings in the absence of pregnancy.
  • hCG levels are also a component of the triple test, a screening test for certain fetal chromosomal abnormalities/birth defects.
  • 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).
    • Giacomello F, Magliocchetti P, Loyola G, Giovarruscio M (1993). “[Serum beta hCG levels and transvaginal echography in the early phases of pregnancy]”. Minerva Ginecol (in Italian). 45 (7–8): 333–7. PMID 8414139.

Uses

Tumor marker

Fertility

  • 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[citation needed] are used to stimulate the Leydig cells to synthesize testosterone. The intratesticular testosterone is necessary for spermatogenesis from the sertoli cells. Typical uses for HCG in men include hypogonadism and fertility treatment, including during testosterone replacement therapy to restore or maintain fertility and prevent testicular atrophy.
  • Several vaccines against human chorionic gonadotropin (hCG) for the prevention of pregnancy are currently in clinical trials.
    • Talwar GP, Gupta JC, Rulli SB, Sharma RS, Nand KN, Bandivdekar AH, Atrey N, Singh P (2015). “Advances in development of a contraceptive vaccine against human chorionic gonadotropin”. Expert Opinion on Biological Therapy. 15 (8): 1183–90. doi:10.1517/14712598.2015.1049943. PMID 26160491. S2CID 10315692.

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 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.
  • 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.
  • 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

  • When exogenous AAS 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.
  • 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.
    • van Breda E, Keizer HA, Kuipers H, Wolffenbuttel BH (April 2003). “Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study”. Int J Sports Med. 24 (3): 195–6. doi:10.1055/s-2003-39089. PMID 12740738.
  • In males, HCG helps restore and maintain testosterone production in the testes by mimicking LH and triggering the production and release of testosterone.
  • If HCG is used for too long and in too high a dose, the resulting rise in natural testosterone and estrogen would eventually inhibit endogenous production of luteinizing hormone via negative feedback on the hypothalamus and pituitary gland.[citation needed]

HCG diet

  • British endocrinologist Albert T. W. Simeons proposed HCG as an adjunct to an ultra-low-calorie weight-loss diet (fewer than 500 calories).
    • Simeons AT (2010). Pounds & Inches: A New Approach To Obesity. Popular Publishing. ISBN 978-0-615-42755-3.
  • Simeons, while studying pregnant women in India on a calorie-deficient diet, and “fat boys” with pituitary problems (Frölich’s syndrome) treated with low-dose HCG, observed that both lost fat rather than lean (muscle) tissue.
    • Simeons AT (2010). Pounds & Inches: A New Approach To Obesity. Popular Publishing. ISBN 978-0-615-42755-3.
  • 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.
    • Simeons AT (2010). Pounds & Inches: A New Approach To Obesity. Popular Publishing. ISBN 978-0-615-42755-3.
  • 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.
  • 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
  • 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.

Homeopathic HCG for weight control

  • Controversy about, and shortages
  • 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.

Tetanus vaccine conspiracy theory

See also

External links

Merck Serono
PDB gallery
GnRH and gonadotropins
Assisted reproductive technology
Hormones
GnRH and gonadotropin receptor modulators

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From Wikipedia where page was last edited on 17 August 2022

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