Gonadotropin, Chorionic

AHFS Class: Gonadotropins (68:18)

ATC Class: G03GA08
VA Class: HS400

CG

hCG

HCG

View the associated Essentials monograph.

Introduction

Chorionic gonadotropin (CG) is a gonad-stimulating polypeptide hormone secreted by the placenta, that is obtained from urine of pregnant women.

Uses

Prepubertal Cryptorchidism and Hypogonadotropic Hypogonadism in Males

In males, chorionic gonadotropin (CG) is used for the treatment of prepubertal cryptorchidism that is not caused by anatomical obstruction. In general, CG is thought to induce testicular descent in patients in whom descent would have occurred at puberty; therefore, CG may be useful diagnostically to predict whether or not orchiopexy will be required in the future. CG-induced testicular descent is usually only temporary; however, the response may be permanent in some patients. Although it is generally agreed that corrective therapy for cryptorchidism must be started before pubescence to prevent irreparable testicular damage, opinions differ regarding the optimum age for treatment; the manufacturers state that CG therapy for prepubertal cryptorchidism is usually instituted in patients 4–9 years of age.

CG is also used in appropriately selected males for the management of hypogonadotropic hypogonadism resulting from pituitary deficiency.

Infertility

CG is used in combination with menotropins to stimulate spermatogenesis in males with primary or secondary hypogonadotropic hypogonadism who have been appropriately pretreated with CG. CG/menotropins therapy has been shown to be effective in inducing spermatogenesis in males with primary hypogonadotropic hypogonadism resulting from a congenital factor or prepubertal hypophysectomy and in males with secondary hypogonadotropic hypogonadism resulting from hypophysectomy, craniopharyngioma, cerebral aneurysm, or chromophobe adenoma.

In females, CG is used to induce ovulation and pregnancy in anovulatory, infertile patients in whom the cause of anovulation is secondary to pituitary insufficiency and not resulting from primary ovarian failure, and who have been appropriately pretreated with menotropins. CG has also been used for the treatment of infertility resulting from corpus luteum deficiency.

Other Uses

CG has not been shown to be effective as adjunctive therapy for the treatment of obesity. There is no substantial evidence that the drug increases weight loss beyond that resulting from caloric restriction alone, causes a more attractive or “normal” distribution of body fat, or decreases the hunger and discomfort associated with calorie-restricted diets.

Dosage and Administration

Reconstitution and Administration

Chorionic gonadotropin (CG) is administered only by IM injection.

Chorionic gonadotropin powder for injection is reconstituted with the diluent provided according to the manufacturer’s directions.

Dosage

Dosage of chorionic gonadotropin is expressed in terms of USP units. Dosage regimens of chorionic gonadotropin vary widely, and dosage must be carefully individualized based on the condition being treated, age and weight of the patient, and the clinician’s judgment.

Prepubertal Cryptorchidism

For the treatment of prepubertal cryptorchidism that is not caused by anatomical obstruction, the following CG dosage regimens have been suggested: 4000 USP units 3 times weekly for 3 weeks; 5000 USP units every other day for 4 doses; or 15 doses of 500–1000 USP units given over a period of 6 weeks. Alternatively, 500 USP units may be given 3 times weekly for 4–6 weeks; if this course of therapy is not successful, a subsequent course of CG therapy may be given 1 month later using doses of 1000 USP units in the same regimen.

Hypogonadotropic Hypogonadism

For the management of hypogonadotropic hypogonadism resulting from pituitary deficiency in appropriately selected males, the following dosage regimens have been suggested: 500–1000 USP units 3 times weekly for 3 weeks, followed by the same dose 2 times weekly for 3 weeks; or 4000 USP units 3 times weekly for 6–9 months, followed by 2000 USP units 3 times weekly for 3 months.

Stimulation of Spermatogenesis

For information on dosage of CG when used in combination with menotropins to stimulate spermatogenesis in males with primary or secondary hypogonadotropic hypogonadism, see Stimulation of Spermatogenesis in Dosage and Administration: Dosage, in Menotropins 68:18.

Induction of Ovulation and Pregnancy

To induce ovulation and pregnancy in anovulatory, infertile females in whom the cause of anovulation is secondary to pituitary insufficiency and not resulting from primary ovarian failure, the usual dose of CG is 5000–10,000 USP units given 1 day following the last dose of menotropins. For information on dosage of menotropins when used in conjunction with CG to induce ovulation and pregnancy, see Induction of Ovulation and Pregnancy in Dosage and Administration: Dosage, in Menotropins 68:18.

Cautions

Adverse Effects

Chorionic gonadotropin (CG) is generally well tolerated following administration of usual therapeutic doses. Adverse effects of CG include headache, irritability, restlessness, depression, fatigue or tiredness, edema, gynecomastia, aggressive behavior, and pain at the injection site. Precocious puberty may occur in prepubertal males receiving the drug.

Precautions and Contraindications

Since androgen secretion induced by CG may result in fluid retention, CG should be used with caution in patients with asthma, seizure disorders, migraine, or cardiac or renal disease.

Prepubertal males should be carefully monitored during CG therapy, since induction of androgen secretion by CG may induce precocious puberty in these patients being treated for cryptorchidism. If signs of precocious puberty (phallic enlargement, testicular enlargement and redness, development of pubic hair, aggressive behavior) occur, CG should be discontinued; these changes are reversible within 4 weeks of the last injection of CG.

CG may interfere with radioimmunoassays for gonadotropins, particularly luteinizing hormone. Individual laboratories should establish the degree of cross-reactivity with their gonadotropin assay, and physicians requesting gonadotropin levels for patients on CG should inform the laboratory regarding such therapy.

CG should be used in conjunction with menotropins only by physicians who are experienced in the management of fertility disorders and who are familiar with the criteria for patient selection and the cautions, precautions, and contraindications associated with CG/menotropins therapy. The principal serious adverse effects associated with CG/menotropins therapy include ovarian hyperstimulation, a syndrome consisting of sudden ovarian enlargement, ascites with or without pain, and/or pleural effusion; enlargement of preexisting ovarian cysts or rupture of ovarian cysts with resultant hemoperitoneum; and arterial thromboembolism secondary to hyperestrogenism. In addition, there is an increased incidence of multiple ovulations with resulting plural gestations associated with CG/menotropins therapy. For further information on cautions, precautions, and contraindications of CG/menotropins therapy, see Cautions in Menotropins 68:18 and prescribing information for menotropins.

CG is contraindicated in patients with precocious puberty, or carcinoma of the prostate or other androgen-dependent neoplasia. CG is also contraindicated in patients who have experienced an allergic reaction to the drug and in pregnant women. (See Cautions: Pregnancy, in Menotropins 68:18.)

Pediatric Precautions

Safety and effectiveness of CG in children younger than 4 years of age have not been established.

Mutagenicity and Carcinogenicity

Defects of forelimbs and of the CNS, and alterations in sex ratio reportedly have occurred in mice receiving combined gonadotropin and CG therapy in dosages intended to induce superovulation. Mutagenic effects of CG have not been clearly established in humans. Testicular tumors have been reported occasionally in otherwise healthy young men receiving CG for secondary infertility, but a causal relationship between CG and the development of such tumors has not been established.

Pregnancy and Lactation

Pregnancy

Chorionic gonadotropin (CG) may cause fetal toxicity when administered to a pregnant woman. (See Cautions: Pregnancy, in Menotropins 68:18.)

Lactation

Since it is not known whether chorionic gonadotropin is distributed into human milk, the drug should be used with caution in nursing women.

Pharmacology

The principal pharmacologic effects of chorionic gonadotropin (CG) are virtually identical to those of luteinizing hormone (LH); however, CG also appears to exhibit minimal follicle-stimulating hormone (FSH) activity. The mechanism of action of CG appears to be similar to that of LH.

In males, administration of CG stimulates differentiation of, and androgen production by, the interstitial cells (Leydig cells) of the testes; the drug also causes differentiation and early maturation of the cells lining the seminiferous tubules (spermatogenic and Sertoli cells) of the testes. Androgenic stimulation produced by CG results in the development of secondary sex characteristics in prepubertal males and may stimulate testicular descent when no anatomical obstruction is present; this descent is usually reversible following discontinuance of CG.

During the normal menstrual cycle, LH and FSH are responsible for the development and maturation of the normal ovarian follicle, and the abrupt midcycle increase in LH concentration is responsible for ovulation; CG can substitute for LH in this function. During a normal pregnancy, CG secreted by the placenta maintains the corpus luteum following the decreased secretion of LH, supporting continued secretion of estrogen and progesterone and preventing menstruation; however, as placental secretion of estrogen and progesterone increases during the third month of pregnancy, the ovaries and corpus luteum become unessential to the maintenance of gestation. Secretion of CG during pregnancy prevents the growth or maturation of ovarian follicles; no further changes suggesting luteinization of the granulosa or of thecal or stromal elements of the ovaries occur.

CG has no known effect on appetite or sense of hunger, or on mobilization or distribution of body fat.

Pharmacokinetics

Absorption

Because of its polypeptide nature, chorionic gonadotropin (CG) is destroyed in the GI tract, and therefore must be administered parenterally. Following IM administration, an increase in serum CG concentrations may be observed within 2 hours; peak CG concentrations occur within about 6 hours and persist for about 36 hours. Serum CG concentrations begin to decline at 48 hours and approach baseline (undetectable) levels after about 72 hours.

Distribution

Following IM administration of CG, the drug is distributed mainly into the testes in males and into the ovaries in females; smaller amounts of the drug may also be distributed into the proximal tubules of the renal cortex.

Elimination

Blood concentrations of CG decline in a biphasic manner. The half-life in the initial phase (t_½α) is reported to be about 11 hours, and the half-life in the terminal phase (t_½β) is reported to be about 23 hours. Following IM administration of therapeutic doses, approximately 10–12% of the dose is excreted in urine within 24 hours; detectable amounts may continue to be excreted in urine for up to 3–4 days.

Chemistry and Stability

Chemistry

Chorionic gonadotropin (CG) is a gonad-stimulating polypeptide hormone secreted by the placenta. The drug is obtained from urine of pregnant women. Like the other gonadotropins and thyroid-stimulating hormone (TSH), CG is a glycoprotein and is composed of nonidentical and noncovalently linked α and β subunits. The α subunit of CG is essentially identical to the α subunits of the human pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to the α subunit of human TSH; however, the β subunit of CG differs in amino acid sequence from these other hormones.

Chorionic gonadotropin is standardized according to its ability to increase the weight of the uterus in normal, immature female rats as compared to a USP Chorionic Gonadotropin Reference Standard. Potency is expressed in USP units. Chorionic gonadotropin contains at least 1500 USP units/mg. One USP unit is equivalent to 1 International Unit of the World Health Organization.

Chorionic gonadotropin occurs as a white or practically white, amorphous powder and is freely soluble in water. Chorionic gonadotropin for injection is a sterile, dry mixture of the drug with suitable diluents and buffers and occurs as a white or practically white, amorphous, lyophilized powder. Chorionic gonadotropin powder for injection is freely soluble in water and practically insoluble in alcohol. Following reconstitution with the sterile diluent provided, the commercially available injections have a pH of 6–8 and may contain phenol and/or benzyl alcohol as preservatives, and lactose or mannitol; sodium hydroxide, hydrochloric acid, or monobasic or dibasic sodium phosphate may be added during manufacture of the powder for injection to adjust the pH.

Stability

Chorionic gonadotropin powder for injection should be stored at a temperature less than 40°C, preferably between 15–30°C. Following reconstitution with the diluent provided, solutions of the drug are stable for 30–90 days, depending on the specific preparation, when stored at 2–15°C.

Preparations

Chorionic Gonadotropin

Routes	Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IM use only	5000 USP units	Profasi® HP (with bacteriostatic water for injection with benzyl alcohol diluent)	Serono
		10,000 USP units*	Pregnyl® (with bacteriostatic water for injection with benzyl alcohol diluent)	Organon

* available by nonproprietary name

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit www.drugstore.com.

Novarel 10000UNIT/10ML Solution for Reconstitution (FERRING): 1/$50.39 or 3/$138.06

Pregnyl 10000UNIT Solution for Reconstitution (ORGANON): 1/$60.7 or 3/$158.23

Selected Revisions January 2006, © Copyright, July 1971, American Society of Health-System Pharmacists, Inc. 7272 Wisconsin Avenue, Bethesda, MD 20814.