Chorionic Gonadotrophin

What Is Chorionic Gonadotropin?

Chorionic gonadotropin, often called hCG, is a hormone produced by cells in the placenta during pregnancy. It plays a crucial role in supporting and maintaining pregnancy. The hormone hCG is typically detectable in a woman’s blood and urine shortly after conception, and it is the basis for many pregnancy tests.

HCG is one of the earliest markers of pregnancy. Its levels rise rapidly in the early weeks of pregnancy, doubling approximately every 48 to 72 hours.

In the early stages of pregnancy, hCG helps maintain the corpus luteum, a structure in the ovary that produces progesterone. Progesterone is crucial for supporting the uterine lining and preventing its breakdown, essential for a developing pregnancy.

Home pregnancy tests work by detecting the presence of hCG in urine. Blood tests can also measure hCG levels, providing more precise information about the hormone concentration.

In certain medical situations, hCG may be used for therapeutic purposes. For example, it is sometimes prescribed to stimulate ovulation in fertility treatments.

HCG is produced by trophoblast cells, which form the blastocyst’s outer layer and later develop into the placenta.

The levels of hCG in the blood and urine can vary widely among pregnant individuals. The concentration of hCG tends to peak around 8 to 11 weeks of pregnancy and then gradually decline.

It’s important to note that hCG is not only a marker of pregnancy but also has essential functions in supporting the early stages of fetal development. Monitoring hCG levels is often part of prenatal care, and deviations from expected patterns can sometimes indicate potential issues with the pregnancy.

Pharmacokinetics

Peak concentrations of chorionic gonadotrophin occur about 6 hours after an intramuscular dose and 16 to 20 hours after a subcutaneous injection. It is distributed primarily to the gonads. Blood concentrations decline biphasically, with half-lives of about 6 to 11 hours and 23 to 38 hours, respectively. Chorionic gonadotrophin is metabolized mainly in the kidneys. About 10 to 12% of an intramuscular dose is excreted in urine within 24 hours.

After subcutaneous doses, choriogonadotropin alfa has a bioavailability of about 40%. It is metabolized and excreted similarly to chorionic gonadotropin.

Uses and Administration

Chorionic gonadotrophin is a hormone produced by the placenta and obtained from the urine of pregnant women. Its effects are mainly those of the gonadotrophin, a luteinizing hormone, which is responsible for triggering ovulation and formation of the corpus luteum in women and stimulates the production of testosterone by the testes in men. It is usually еуыеувby intramuscular injection, although the subcutaneous route has also been used. Choriogonadotropin alfa is a recombinant form of chorionic gonadotrophin.

In women with anovulatory infertility due to absent or low concentrations of gonadotrophins, chorionic gonadotrophin is given to induce ovulation after follicular development has been stimulated with follicle-stimulating hormone or human menopausal gonadotrophins. Intramuscular injection gives a dose of 5,000 to 10,000 units of chorionic gonadotrophin to mimic the midcycle peak of luteinizing hormone, which typically stimulates ovulation. Up to 3 repeat injections of up to 5,000 units each may be given within nine days to prevent corpus luteum insufficiency. Chorionic gonadotropin is also given with menotropins as an adjunct to IVF procedures and other assisted conception techniques involving superovulation and oocyte collection.

Choriogonadotropin alfa is used similarly to induce ovulation in treating anovulatory infertility or as an adjunct to IVF procedures and other assisted conception techniques. A single dose of 250 micrograms is given by subcutaneous injection when optimal stimulation of follicular growth is achieved.

In males, chorionic gonadotrophin has been used to treat prepubertal cryptorchidism. Regimens vary widely, but doses usually range from 500 to 4000 units thrice weekly by intramuscular injection. Treatment should continue for 1 to 2 months after testicular descent.

Chorionic gonadotropin is also given for male infertility associated with hypogonadotrophic hypogonadism. Again, there is considerable variation in the dosage regimen, and doses have varied from 500 to 4000 units two or three times weekly by intramuscular injection. A drug with follicle-stimulating activity, such as menotrophin, is often added to enable normal spermatogenesis.

In treating delayed puberty associated with hypogonadism in males, an initial dose of chorionic gonadotrophin 500 to 1500 units is given twice weekly by intramuscular injection. The dose should be titrated against plasma-testosterone concentration.

Cryptorchidism

Although surgery remains the treatment with the best success rate, primary hormonal therapy with chorionic gonadotrophin is widely used for cryptorchidism (p.2079). Systematic reviews suggest a success rate of about 20% overall, although this may be reduced when care is taken to exclude retractile testes.

There is some suggestion that medical treatment before or after surgery can improve the patient’s fertility index, a predictor of future fertility. Chorionic gonadotrophin may also be used as an adjuvant before surgery to render the testes palpable, but changes suggestive of inflammation in the testis have been reported following such treatment.

Delayed Puberty

Chorionic gonadotrophin may be appropriate in boys with delayed puberty due to hypogonadotropic hypogonadism.

Infertility

In women with anovulatory infertility, chorionic gonadotrophin and choriogonadotropin alfa can provoke ovulation and provide luteal support once the maturation of a suitable number of follicles has been stimulated by other means. They are used similarly in the various protocols for assisted reproduction. However, use is not recommended for assisted reproduction in patients at risk of ovarian hyperstimulation, such as those with polycystic ovary syndrome. In men with hypogonadotropic hypogonadism, chorionic gonadotrophin stimulates and maintains spermatogenesis. Managing male and female infertility, including the role of chorionic gonadotrophin, is discussed on p.2080.

Malignant Neoplasms

Control of Kaposi’s sarcoma has been reported in a few patients given high-dose intramuscular chorionic gonadotrophin, but regrowth occurred when dosage was reduced or withdrawn. Another study, using lower doses, was stopped due to toxicity and lack of benefit, but others have confirmed benefit after intralesional injection. Some suggest that preparations vary in their activity against the tumor and that it is not chorionic gonadotrophin itself. Still, some impurities (perhaps a ribonuclease or the degradation product of the β-subunit) that is the active principle. Some contaminants may have a stimulant effect on the neoplasm, contributing to the variable results.

Obesity

A meta-analysis involving 24 studies concluded that there was no evidence that chorionic gonadotrophin was effective in treating obesity.

Testicular Function

Chorionic gonadotropin assesses testicular function in suspected primary hypogonadism and incomplete masculinization. The BNFC states that for children one month to 18 years of age, a dose of 1500 to 2000 units may be given once daily for three days (short stimulation test) or twice weekly for three weeks (prolonged test).

Adverse Effects and Precautions

Adverse effects reported with chorionic gonadotrophin include headache, tiredness, changes in mood, depression, restlessness, edema (especially in males), and pain on injection. Treatment for cryptorchidism may produce premature epiphyseal closure or precocious puberty. Gynaecomastia has been reported. In severe cases, ovarian hyperstimulation may occur with marked ovarian enlargement or cyst formation, acute abdominal pain, ascites, pleural effusion, hypovolaemia, shock, and thromboembolic disorders.

Chorionic gonadotrophin should be given with care to patients in whom androgen-induced fluid retention might be a hazard, as in asthma, epilepsy, migraine, or cardiovascular disorders, including hypertension or renal disorders. Hypersensitivity reactions may occur, and it is recommended that patients suspected to be susceptible should be given skin tests before treatment. It should not be given to patients with disorders exacerbated by androgen release, such as prostate carcinoma or precocious puberty. Use should also be avoided in the presence of breast, uterine, ovarian, and testicular tumors and tumors of the hypothalamus, pituitary, thyroid, and adrenal glands.

Drug Approvals

(British Approved Name, rINN)

International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish): CG; Choriogonadotrophin; Chorionic Gonadotropin; Chorioninis gonadotropinas; Gonadotrofina coridnica; Gonadotrophine Chorionique; Gonadotrophinum Chorionicum; Gonadotropin choriovy; Gonadotropine chorionique; Gonadotropinum chorionicum; hCG; Human Chorionic Gonadotrophin; Koriongonadotropiini; Koriongonadotropin; Korion-gonadotropin; Koriyonik Gonadotrofin; Pregnancy-urine Hormone; PU.

CAS — 9002-61-3

ATC — G03GA01

Pharmacopoeias. In China, Europe, Japan, and US.

European Pharmacopoeia, 6th ed. (Gonadotrophin, Chorionic). A dry preparation of placental glycoproteins extracted from the urine of pregnant women. The potency is at least 2500 units/mg. A white to yellowish-white, amorphous powder. Soluble in water. Store at 2° to 8° in airtight containers. Protect from light.

The United States Pharmacopeia 31, 2008 (Chorionic Gonadotropin). A gonad-stimulating polypeptide hormone obtained from the urine of pregnant women. It has a potency of not less than 1500 USP units/mg. A white or practically white, amorphous powder. Freely soluble in water. Store in airtight containers at 2° to 8°.

Choriogonadotropin Alfa

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

INNs in main languages (French, Latin, and Spanish): Choriogonadotropine Alfa; Choriogonadotropinum Alfa; Coriogonadotropina alfa.

CAS — 177073-44-8 (choriogonadotropin alfa); 56832-30-5 (α subunit) 56832-34-9 (β subunit).

ATC — G03GA08.

Preparations

British Pharmacopoeia 2008: Chorionic Gonadotrophin Injection

The United States Pharmacopeia 31, 2008: Chorionic Gonadotropin for Injection.

Proprietary Preparations

Argentina: Dinaron Endocorion Gonacor Ovidrel Pregnyl Profasi

Australia: Ovidrel Pregnyl Profasi

Austria: Pregnyl Profasi

Belgium: Choragon Ovitrelle Pregnyl

Brazil: Choragon Ovidrel Pregnyl Profasi HP

Canada: Pregnyl Profasi HP

Chile: APL Gonacor Ovidrel Pregnyl Profasi

Czech Republic: Ovitrelle Praedynf Pregnyl Profasi

Denmark: Ovitrelle Pregnyl Profasi

Finland: Ovitrelle Pregnyl Profasi

France: Ovitrelle

Germany: Choragon Ovitrelle Predalon Pregnesin+ Primogonyl

Greece: Ovitrelle Pregnyl Profasi

Hong Kong: Choragon Choriomon Ovidrel Pregnyl Profasi

Hungary: Choragon Ovitrelle Pregnyl Profasi

India: Corion Profasi Proligon Provigil Pubergen

Indonesia: Ovidrel Pregnyl

Ireland: Ovitrelle Pregnyl Profasi

Israel: Chorigon Ovitrelle Pregnyl

Italy: Gonasi HP Ovitrelle Pregnyl Profasi HP

Malaysia: Choragon Ovidrel Pregnyl Profasi

Mexico: Choragon Choriomon Gonadotropyl Op, Ovidrel Pregnyl Profasi

The Netherlands: Choragon Ovitrelle Pregnyl Profasi

Norway: Ovitrelle Pregnyl Profasi

New Zealand: Ovidrel Profasi

Philippines: Ovidrel Pregnyl

Poland: Choragon Ovitrelle Pregnyl

Portugal: Ovitrelle Pregnyl Profasi HP

Russia: Choragon Ovitrelle Pregnyl

South Africa: APL Pregnyl Profasi

Singapore Ovidrel Pregnyl Profasi

Spain: Ovitrelle Profasi HP

Sweden: Ovitrelle Pregnyl Profasi

Switzerland: Choriomon Ovitrelle Pregnyl Profasi

Thailand: IVF-C Ovidrel Pregnyl Profasi

Turkey: Choragon Ovitrelle Pregnyl

United Kingdom: Choragon Ovitrelle Pregnyl

USA: Chorexf Choron Gonic Novarel Ovidrel Pregnyl Profasi

Venezuela: Ovidrel Pregnyl Profasi.

Multi-ingredient

Germany: NeyNormin N (Revitorgan-Dilutionen N Nr 65)

Mexico: Gonakor

The symbol denotes a preparation no longer actively marketed.