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  • CLASSES

    Gonadotropins

    DEA CLASS

    Rx

    DESCRIPTION

    Gonad-stimulating hormone secreted by the placenta during pregnancy; obtained from the urine of pregnant women; recombinant form now available; HCG mimics the actions of LH; HCG induces an LH surge after the use of ovulation induction protocols in women; also used to treat hypogonadism and oligospermia in men.

    COMMON BRAND NAMES

    Novarel, Ovidrel, Pregnyl

    HOW SUPPLIED

    Chorionic Gonadotropin/Novarel/Pregnyl Intramuscular Inj Pwd F/Sol: 5000U, 10000U
    Ovidrel Subcutaneous Inj Sol: 0.5mL, 250mcg

    DOSAGE & INDICATIONS

    For the treatment of male infants and children with prepubertal cryptorchidism not caused by anatomical obstruction.
    NOTE: HCG appears to be more effective at inducing testicular descent in those infants and children with palpable testes in the high scrotal, prescrotal, or inguinal regions. Intra-abdominal testes are especially refractory to HCG treatment. While hormonal therapy is traditionally instituted after the age of 4 years, there are several studies that include male children of younger ages, and there is some evidence that treatment prior to age 2 years may be beneficial in terms of long-term outcomes. Consult specialized references for the most current recommendations.
    Intramuscular dosage
    Children (males) >= 6 years

    The International Health Foundation has advocated a dosage of 1000 USP units IM 2 times per week for a total of 5 weeks. NOTE: various dosage regimens have been advocated for male children >= 4 years old. The following alternative regimens have been employed; however, the total dosage and length of the treatment course may vary widely: 1) 4000 USP units IM 3 times per week for 3 weeks; 2) 5000 USP units IM every other day for 4 doses; 3) 15 doses of 500—1000 USP units IM given over a period of 6 weeks; or 4) administer 500 USP units IM 3 times per week for 4—6 weeks. If not successful, then another course of HCG 1 month later may be administered at doses of 1000 USP units IM 3 times per week for 4—6 weeks.

    Children (males) 1—5 years

    The International Health Foundation has advocated a dosage of 500 USP units IM 2 times per week for a total of 5 weeks.

    Infants (males) 6—12 months

    The International Health Foundation has advocated a dosage of 250 USP units IM 2 times per week for a total of 5 weeks.

    For the treatment of select cases of hypogonadotropic hypogonadism.
    For the routine treatment of hypogonadotropic hypogonadism in adult and adolescent males.
    Intramuscular or Subcutaneous† dosage
    Adults and Adolescent males

    NOTE: various dosage regimens have been advocated. The following alternative regimens have been employed; however, the total dosage and length of the treatment course may vary widely: 1) 500—1000 USP units IM or subcutaneous 3 times per week for 3 weeks, followed by the same dose twice per week for 3 weeks; 2) 4000 USP units IM or subcutaneous 3 times per week for 6—9 months, then reduced to 2000 USP units 3 times a week for an additional 3 months; or 3) HCG 2500 units subcutaneous 2 times per week in combination with FSH 150 International Units subcutaneous 3 times per week for at least 6 months.

    For the stimulation of spermatogenesis in males with primary or secondary hypogonadotropic hypogonadism and resultant oligospermia.
    NOTE: Pretreatment with human chorionic gonadotropin (HCG) is required prior to combination treatment with menotropins or follitropin. Various dosage regimens have been advocated.
    Intramuscular or Subcutaneous† dosage (pretreatment with HCG)
    Adult males

    Pretreatment with 1000—2250 USP units IM/subcutaneous 2—3 times per week; dosages up to 5000 USP units of HCG IM 3 times per week. Administer until normal serum testosterone concentrations are achieved and masculinization (development of secondary sex characteristics) occurs. Pretreatment may require 4—6 months, followed by combined therapy with menotropins (hMg) or follitropin (r-hFSH). See the following regimens. In some patients with appropriate testicular volumes (i.e., > 4 mL), HCG treatment alone may produce adequate spermatogenesis.

    Intramuscular or Subcutaneous† dosage (HCG combined with menotropins therapy following HCG pretreatment)
    Adult males

    NOTE: various dosage regimens have been advocated. The following alternative regimens have been employed; however, the total dosage and length of the treatment course may vary widely. ONE REGIMEN: HCG 1000—1500 USP units administered IM/subcutaneous in combination with menotropins 75—150 International Units IM/subcutaneous. Both are administered every other day, but at separate sites. Combination therapy should be continued for at least 4 months to ensure detection of spermatozoa in the ejaculate and to increase testicular volume. Most men in clinical trials to date are noted to have sperm output by 6 months; target goals are reached with a median 9 months of treatment. ALTERNATIVE REGIMEN: HCG 2000 USP units administered IM/subcutaneous 2 times per week in combination with menotropins 75 International Units IM/subcutaneous given 3 times per week at a separate injection site. Combination therapy should be continued for at least 4 months to ensure detection of spermatozoa in the ejaculate. If an increase in spermatogenesis has not occurred in 4 months, the dosage of menotropins can be increased to 150 International Units IM 3 times per week or continued while the dose of HCG remains the same.

    Intramuscular or Subcutaneous† dosage (HCG combined with follitropin-alfa, FSH therapy following HCG pretreatment)
    Adult males

    FSH must be given in conjunction with hCG. Both drugs are administered roughly 3 times per week (i.e., every other day) but at separate sites. The recommended dose is HCG 1000—1500 USP units (or the dose required to maintain normal serum testosterone) administered IM or subcutaneous 3 times per week in combination with follitropin-alfa 150 International Units subcutaneous 3 times per week at different sites. The lowest dose of FSH which induces spermatogenesis should be utilized. If azoospermia persists, the dose of FSH may be increased to a maximum dose of 300 International Units 3 times per week. Combination therapy should be continued for at least 4 months to ensure detection of spermatozoa in the ejaculate and to increase testicular volume. Most men in clinical trials to date were noted to have sperm output by 6 months; target goals adequate for fertilization are reached with a median 9 months of treatment. The drugs may need to be administered for up to 18 months to achieve adequate spermatogenesis.

    Subcutaneous† dosage (HCG combined with follitropin-beta, FSH therapy following HCG pretreatment)
    Adult males

    FSH must be given in conjunction with hCG. Initially, give hCG 1500 International Units subcutaneous twice per week. If serum testosterone concentrations have not normalized after 8 weeks, the hCG dose may be increased to 3000 International Units subcutaneous twice per week. Give hCG at the dose needed to normalize serum testosterone concentrations in combination with follitropin-beta 225 International Units subcutaneous twice weekly or 150 International Units subcutaneous 3 times per week.

    For adjunctive treatment of anovulation in females with infertility not due to primary ovarian failure, including in women undergoing assisted reproductive technology (ART).
    NOTE: HCG must be withheld if there is an excessive ovarian response, as evidenced by abnormally enlarged ovaries, multiple follicular development, or excessive estradiol production. Consult specialized references.
    For induction of ovulation in females treated with clomiphene who have an appropriate follicular response but a failure to ovulate.
    Intramuscular dosage (urine-derived products)
    Adult females

    5000—10,000 USP units of HCG IM as a single dose at the appropriate day, as determined by exam and ultrasound, after the last dose of clomiphene (usually 3—4 days after the last clomiphene dose).

    For induction of ovulation following treatment with menotropins or follitropin in females with infertility.
    Intramuscular dosage (urine-derived products)
    Adult females

    5000—10,000 USP units of HCG IM as a single dose 1 day after the last dose of menotropins or FSH pre-treatment. The labeling for menotropins recommends an HCG dosage of 10,000 USP units for anovulation.

    Subcutaneous dosage (Ovidrel recombinant- hCG)
    Adult females

    250 mcg subcutaneous as a single dose 1 day after the last dose of menotropins or FSH pre-treatment.

    For luteal phase support† of infertile female patients with hypogonadotropic hypogonadism after they have completed a typical ovulation induction protocol with FSH/LH (menotropins).
    Intramuscular dosage (urine-derived products)
    Adult females

    2500 USP units of HCG IM given as a single dose 8 days after the initial dose of HCG was given.

    For induction of final oocyte maturation in preparation for oocyte harvest in females undergoing IVF or other ART procedures following follitropin treatment.
    Intramuscular dosage (urine-derived products)
    Adult females

    When a sufficient number of follicles of adequate size are present with FSH therapy, FSH is discontinued and the final maturation of the follicles is induced by administering 5000—10,000 USP units of HCG IM as a single dose 1 day after the last dose of FSH. Oocyte retrieval is usually performed 34—36 hours later, before ovulation can occur.

    Subcutaneous dosage (Ovidrel recombinant- hCG ONLY)
    Adult females

    When a sufficient number of follicles of adequate size are present with follicle-stimulating therapy, the follicle-stimulating hormone is discontinued and the final maturation of the follicles is induced by administering 250 mcg subcutaneous of Ovidrel as a single dose 1 day after the last dose of of the follicle-stimulating agent. Oocyte retrieval is usually performed 34—36 hours later, before ovulation can occur.

    For the treatment of Kaposi's sarcoma†.
    Intralesional dosage†
    Adults

    In an early phase I-II clinical trial, dosages of 250—2000 USP units of HCG were injected directly into the Kaposi's lesions. A placebo was injected into a third lesion. The intralesional dosage was repeated 3 times per week for 2 weeks. Regression of tumor occurred only in the HCG-treated lesions and in a dose-dependent manner; the 2000 USP unit dosage produced the greatest tumor regression and apoptosis.

    †Indicates off-label use

    MAXIMUM DOSAGE

    No specific maximum dosage limit recommendations are available. Dosage regimens of urine-derived human chorionic gonadotropin (HCG) depend upon the patient's age, sex, weight, condition being treated, product chosen, and the prescribing clinician's judgment. Therefore, doses may vary widely and must be carefully individualized.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    NOTE: Dosage regimens of human chorionic gonadotropin (HCG) depend upon the patient's age, sex, weight, condition being treated, and the prescribing clinician's judgment. Therefore, doses may vary widely and must be carefully individualized.
    NOTE: Human chorionic gonadotropin (HCG) should be used only by health care prescribers who are experienced in managing endocrine or fertility disorders and only in facilities where appropriate clinical and endocrinology evaluations are available.
    Hazardous Drugs Classification
    NIOSH 2016 List: Group 3
    NIOSH (Draft) 2020 List: Table 2
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intramuscular Administration

    Urine-derived HCG products
    The preferred route of administration is by intramuscular injection. Although not FDA-approved for subcutaneous administration, some urine-derived products have been used for subcutaneous administration (e.g., for infertility in women, or hypogonadism in males, see Pharmacokinetics). Do not inject intravenously.
     
    Reconstitution for intramuscular (IM) injection:
    Withdraw sterile air from the vial containing the lyophilized powder and inject into the vial containing the sterile diluent provided by the manufacturer. Withdraw up to 10 mL of the sterile diluent and add to the lyophilized vial; agitate gently until powder is completely dissolved. The maximum recommended concentration of the final IM solution should not exceed 2000 USP units/mL. May be stored for up to 30 to 60 days under refrigeration after reconstitution. Storage length varies between manufacturers; consult individual prescribing information.
     
    Intramuscular injection:
    For adults and adolescents, inject deeply into a large muscle. For children and infants 6 months and older, inject deeply into a large muscle, preferably the anterolateral aspect of the thigh.

    Subcutaneous Administration

    Choriogonadotropin Alfa Solution for injection (Ovidrel) ONLY
    Administer by subcutaneous injection only. Do not inject intravenously or intramuscularly.
    Inject subcutaneously as directed in the insert taking care not to inject intradermally or into a blood vessel.
    Subcutaneous injection should be made in the abdomen skin around the navel, where there is a lot of loose skin and layers of fatty tissue.
    Storage: Prior to dispensing to the patient, store Ovidrel Pre-Filled Syringe refrigerated between 2 to 8 degrees C (36 to 46 degrees F). Do not freeze. Patients should store the pre-filled syringe refrigerated to allow the product to be used until the expiration date shown on the syringe or carton. The syringe may be stored by the patient for no more than 30 days at room temperature, up to 25 degrees C (77 degrees F), but must be used within those 30 days. Protect from light. Store in original package. Discard any unused material.

    Other Injectable Administration

    Intralesional Administration
    Human chorionic gonadotropin is not FDA-approved for intralesional administration; however, some products (e.g., A.P.L.) have been used for intralesional administration on an investigational basis for Kaposi's sarcoma. Do not inject any HCG product intravenously.
    Consult specialized references for proper intralesional dosage preparation, administration, and stability.

    STORAGE

    Novarel:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store product reconstituted with BWFI (benzyl alcohol 0.9%) in refrigerator (36-46 degrees F) and use within 30 days
    Ovidrel:
    - After dispensing, refrigeration is recommended but not required if product is stored below 77 degrees F and used within 30 days
    - Discard unused portion. Do not store for later use.
    - Prior to dispensing, store in refrigerator (36 to 46 degrees F)
    - Protect from light
    - Store in original container
    Pregnyl:
    - Reconstituted product is stable for 60 days when refrigerated
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Hamster protein hypersensitivity

    Human chorionic gonadotropin, HCG is contraindicated for use in any patient with a prior history of HCG hypersensitivity. Choriogonadotropin alfa (r-HCG) is contraindicated in patients who have previously demonstrated hamster protein hypersensitivity. r-HCG is manufactured using Chinese hamster ovary cells.

    Benzyl alcohol hypersensitivity, neonates

    Certain urine-derived human chorionic gonadotropin, HCG products (e.g., Pregnyl, Novarel) are packaged with diluents containing Bacteriostatic Water for Injection, USP (i.e., contains benzyl alcohol). Such diluents should be used cautiously in any patient with a history of benzyl alcohol hypersensitivity. Benzyl alcohol has been associated with a fatal 'gasping syndrome' in neonates and premature infants and therefore diluents containing benzyl alcohol should be avoided in these populations.

    Children, precocious puberty

    The safety and effectiveness of human chorionic gonadotropin in children have not been established except as stated for the treatment of male children with cryptorchidism not due to anatomic obstruction. While the manufacturers do not recommend HCG for this use in male children under the age of 4 years, the literature describes HCG treatment protocols in younger children. Consult specialized references for the most current recommendations. Human chorionic gonadotropin, HCG may induce precocious puberty in males treated for cryptorchidism. This risk should be balanced against the expected benefit from the treatment (see Adverse Reactions). Novarel and Pregnyl brand HCG are contraindicated in patients with precocious puberty.

    Asthma, cardiac disease, migraine, renal disease, seizure disorder, thromboembolic disease, thrombophlebitis

    Human chorionic gonadotropin, HCG induces androgen secretion, which can result in fluid retention. Human chorionic gonadotropin should be used with caution in patients with health problems that may be exacerbated by fluid retention, including some patients with asthma, cardiac disease, renal disease, seizure disorder, or migraine headache. Rarely, thromboembolic events have been reported in females receiving medications for controlled ovarian hyperstimulation protocols. HCG should be used extremely cautiously in those patients with active thrombophlebitis or other active thromboembolic disease. Caution is also warranted in patients with risk factors of thromboembolic events such as prior medical or family history. Similar warnings have not been issued for the treatment of hypogonadism or cryptorchidism in males.

    Dysfunctional uterine bleeding, endometrial cancer, endometriosis, neoplastic disease, ovarian cancer, prostate cancer, uterine leiomyomata

    Because of induction of androgen and other hormone secretion, HCG is contraindicated in males with prostate cancer, or any patient with sex hormone-dependent neoplastic disease. Because fertility protocols that include HCG may stimulate the growth of hormone-dependent tissues, HCG administration should be used cautiously in females with abnormal or dysfunctional uterine bleeding or vaginal bleeding of undetermined origin. Moreover, Ovidrel brand HCG is specifically contraindicated in abnormal uterine bleeding of undetermined origin. Neoplastic disease of the reproductive tract and accessory organs (e.g., ovarian cancer or endometrial cancer) should be ruled out before use in females. Endometrial growth may be stimulated by these fertility protocols; they should be used cautiously in patients with uterine leiomyomata (fibroids) or endometriosis. It has been suggested that the use of fertility drugs might increase the risk of certain cancers in females. Some observational studies and a number of case reports gave rise to the speculation that the increased number of ovulatory follicles and/or high gonadotropin and estrogen levels induced by infertility treatment might enhance the development of breast or ovarian cancer. However, infertility alone is an independent risk factor for the development of either breast or ovarian cancer. Case reports also rarely control for other independent confounding factors such as delay in parity or family history. In one long-term cohort study of 1,197 infertile women, the incidence of ovarian or breast cancer was not significantly elevated in the groups receiving fertility treatments versus those not treated. The breast cancer rate, in particular, was not significantly different in either group versus the general female population. While more studies are needed, current data do not support an association between the use of fertility drugs and increased cancer risks.

    Adrenal insufficiency, ovarian failure, pituitary adenoma, thyroid disease

    Ovidrel brand HCG is contraindicated in primary ovarian failure. Females who are determined to have primary ovarian failure are not candidates for infertility treatment protocols that call for ovarian hyperstimulation (e.g., clomiphene, menotropins, or follitropin followed by HCG administration). Ovarian hyperstimulation protocols will only be effective for assisted reproduction in women with an intact ovarian response. Patients with uncontrolled organic intracranial lesions such as pituitary adenoma or other pituitary tumor, uncontrolled thyroid disease or untreated adrenal insufficiency should also not receive hCG; furthermore, Ovidrel is contraindicated in these populations.

    Ascites, ovarian cyst, polycystic ovary syndrome

    Prior to initiation of HCG administration in women undergoing controlled ovarian hyperstimulation, a full gynecologic exam should be performed, including a pelvic ultrasound, to detect the appropriate progression of follicular development and the absence of inappropriate ovarian enlargement. Ovidrel brand HCG is contraindicated in patients with ovarian cyst or ovarian enlargement of undetermined origin. HCG should not be administered to patients with ovarian enlargement or a preexisting ovarian cyst. HCG therapy should not be initiated until the diagnostic cause of the cyst or enlargement has been determined and ovary size has returned to normal. All female patients undergoing controlled ovarian hyperstimulation should be instructed to report symptoms of ovarian enlargement, including abdominal pain or pelvic pain; nausea; vomiting; ascites (fluid and distension in the abdomen); or weight gain immediately. The current cycle of fertility agents should be halted if ovarian enlargement or ovarian hyperstimulation syndrome (OHSS) occurs or if an ovarian cyst develops; maximal ovarian enlargement may not be evident until several days after fertility drug discontinuation. HCG administration should not occur in these patients. However, withholding of HCG does not ensure that OHSS will not occur. Fertility therapy should not be reinstated until ovary size has returned to normal. Complete pelvic exams, including pelvic ultrasounds, should be repeated in all female patients during and prior to each fertility drug cycle. Some patients with polycystic ovary syndrome (PCOS) are unusually sensitive to gonadotropins and may have an exaggerated response to ovarian hyperstimulation protocols.

    Geriatric

    Clinical studies of HCG for the treatment of infertility in women typically do not include a sufficient number of geriatric females. Use with caution in elderly females who are undergoing assisted reproductive technology (ART) procedures.

    Pregnancy

    Human chorionic gonadotropin is used for infertility treatments and is classified in FDA pregnancy category X and is contraindicated after conception has occurred. When administered to mice, animal derived formulations of exogenous HCG have induced a high incidence of external congenital anomalies. While animal data are not always indicative of the response in human gestation, the potential for serious fetal harm cannot be excluded. Therefore, pregnancy should be ruled out prior to the administration of HCG with each fertility treatment course. In addition to potential effects on the fetus, protocols using HCG inherently increase the risk of multiple gestation and the risks associated with such pregnancies.

    Breast-feeding

    Human chorionic gonadotropin, HCG should be used with caution in lactating women who are breast-feeding. Most endogenous gonadotropins are found in breast milk or tissues to some degree. It is neither known whether exogenous HCG is distributed into breast milk, nor what effect this would have on the breast-feeding infant.

    Obesity

    Due to the lack of therapeutic effect and potential risks of therapy, human chorionic gonadotropin, HCG is not to be used for the treatment of obesity. Claims that HCG increases weight loss beyond that from calorie restriction, that it causes a more attractive or normal distribution of fat, or that it decreases the hunger and discomfort associated with calorie restricted diets are not supported by substantial evidence. Numerous data to date suggest the agent is not effective in assisting weight loss.

    Tobacco smoking

    Tobacco smoking is a lifestyle choice that may decrease fertility or the effectiveness of fertility treatments in some women and/or men. Patients should be encouraged to avoid tobacco consumption and pursue smoking cessation while pursuing fertility therapies such as the use of human chorinonic gonadotropin, hCG.

    Hepatic disease, renal impairment

    Safety and efficacy of HCG has not been determined in patients with renal impairment or hepatic disease. In clinical evaluation of recombinant choriogonadotropin alfa injection, elevations in ALT were found in 10 (3%) of 335 patients receiving a 250 mcg dose, 9 (10%) of 89 patients receiving a 500 mcg dose, and in 16 (4.8%) of 328 patients receiving urine-derived hCG. Elevations in ALT ranged up to 1.2 times the upper limit of normal. At this time, the clinical significance of these findings is unknown.

    ADVERSE REACTIONS

    Severe

    ovarian hyperstimulation syndrome / Delayed / 1.7-9.0
    ectopic pregnancy / Delayed / 0-2.0
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    thromboembolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 3.0-10.0
    ovarian enlargement / Delayed / 3.0-3.0
    vaginitis / Delayed / 0-2.0
    vaginal bleeding / Delayed / 0-2.0
    hot flashes / Early / 0-2.0
    edema / Delayed / Incidence not known
    erythema / Early / Incidence not known
    dyspnea / Early / Incidence not known
    precocious puberty / Delayed / Incidence not known
    depression / Delayed / Incidence not known

    Mild

    gynecomastia / Delayed / 0-30.0
    injection site reaction / Rapid / 14.0-16.2
    abdominal pain / Early / 3.0-4.2
    nausea / Early / 3.4-3.4
    vomiting / Early / 2.5-2.5
    breakthrough bleeding / Delayed / 0-2.0
    leukorrhea / Delayed / 0-2.0
    rash / Early / 0-2.0
    pruritus / Rapid / 0-2.0
    mastalgia / Delayed / 0-2.0
    malaise / Early / 0-2.0
    headache / Early / 0-2.0
    dizziness / Early / 0-2.0
    insomnia / Early / 0-2.0
    emotional lability / Early / 0-2.0
    diarrhea / Early / 0-2.0
    flatulence / Early / 0-2.0
    back pain / Delayed / 0-2.0
    urticaria / Rapid / Incidence not known
    restlessness / Early / Incidence not known
    irritability / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    pelvic pain / Delayed / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Human Chorionic Gonadotropin, HCG products.

    PREGNANCY AND LACTATION

    Pregnancy

    Human chorionic gonadotropin is used for infertility treatments and is classified in FDA pregnancy category X and is contraindicated after conception has occurred. When administered to mice, animal derived formulations of exogenous HCG have induced a high incidence of external congenital anomalies. While animal data are not always indicative of the response in human gestation, the potential for serious fetal harm cannot be excluded. Therefore, pregnancy should be ruled out prior to the administration of HCG with each fertility treatment course. In addition to potential effects on the fetus, protocols using HCG inherently increase the risk of multiple gestation and the risks associated with such pregnancies.

    Human chorionic gonadotropin, HCG should be used with caution in lactating women who are breast-feeding. Most endogenous gonadotropins are found in breast milk or tissues to some degree. It is neither known whether exogenous HCG is distributed into breast milk, nor what effect this would have on the breast-feeding infant.

    MECHANISM OF ACTION

    The mechanism of action of human chorionic gonadotropin (hCG) depends upon the purpose for which it is being used, the sex of the patient, and the level of maturity of the patient to whom it is administered.
     
    •Activity - adult females: In select females with infertility , human chorionic gonadotropin has actions essentially identical to those of luteinizing hormone (LH). Human chorionic gonadotropin (hCG) also appears to have additional, though minimal, follicle-stimulating hormone (FSH) activity. By administering hCG after follitropin, menotropins, or clomiphene, the normal LH surge that precedes ovulation can be mimicked. Human chorionic gonadotropin (hCG) promotes the development and maintenance of the corpus lutetium and the production of progesterone. Following hCG administration, final luteinization or maturation of the oocytes occurs and either ovulation can ensue for timed insemination techniques, or oocyte retrieval can take place for assisted reproductive technology (ART) procedures such as in vitro fertilization (IVF). Once pregnancy takes place, endogenous hCG is normally secreted by the placenta to support the continued secretion of female hormones and the corpus luteum.
     
    •Activity - adult and adolescent males: In adult and adolescent men with hypogonadotropic hypogonadism, hCG acts like LH and stimulates testosterone production in the Leydig cells and spermatogenesis in the seminiferous tubules. Stimulation of androgen production by hCG causes development of secondary sex characteristics in males (e.g., deepening of voice, facial hair, etc.). Human chorionic gonadotropin (hCG) also stimulates the Leydig cells to produce estrogens; increased estrogen levels may produce gynecomastia in some males. Once hCG is initiated, it takes at least 70—80 days for germ cells to reach the spermatozoal stage. Response to treatment is also noted by the development of masculine features and the normalization of serum testosterone levels. Induction of testicular growth and increased sperm volumes may help to restore fertility in these men after many months to years of treatment, which is then sometimes combined with the use of either menotropins or follitropin.
     
    •Activity - male infants and children: In the male infant, normal testicular descent is complete by 3 months of age. Testicular descent occurs secondary to an endogenous testosterone surge stimulated by pituitary gonadotropins in response to the discontinued exposure to maternal circulating estrogens upon birth; this testosterone surge peaks within 60 days postnatally. In male infants and children with cryptorchidism, hCG acts like LH and causes the Leydig cells of the testes to produce a testosterone surge and induce the descent of palpable testes. The hormonal stimulation by hCG may result in an early pseudopuberty, and in some cases, the response to hormonal therapy may be temporary in 10—20% of cases. Hormonal therapies like hCG have not replaced the primary surgical treatment for the condition, which is orchiopexy within the first 1—2 years of life. Early animal studies have suggested that hCG may be used as an adjunct to orchiopexy to help preserve fertility, but human data is lacking.
     
    •Activity on body composition (all sexes): Human chorionic gonadotropin has no known effects on appetite, or on mobilization or distribution of body fat. It is not an effective treatment for obesity. In sport, athletes use HCG as an 'undetectable' anabolic steroid; hCG increases the body's production of testosterone and epitestosterone without increasing the ratio of the two hormones in the urine above normal values. Urinary testing is being developed which should allow for discriminate testing of hCG doping in sport.

    PHARMACOKINETICS

    Human chorionic gonadotropin is administered subcutaneously and intramuscularly. Similar to other polypeptides, gonadotropins are almost completely degraded in the gastrointestinal tract; therefore, parenteral administration is required.
    Urine-derived products: In the body, human chorionic gonadotropin primarily distributes into the testes in males and into the ovaries in females. In the ovaries, hCG is concentrated in the fluid of the developing follicles. The metabolic fate of hCG has not been elucidated, but it is eliminated in a biphasic manner. The terminal half-life is approximately 23 hours. After a single IM injection, roughly 10—12% of a dose is excreted unchanged in the urine within 24 hours and can be detected for up to 3—4 days.
    Recombinant hCG: The metabolic fate of r-hCG has not been elucidated, but it is eliminated in a biphasic manner. Recombinant-hCG is eliminated from the body with a mean terminal half-life of roughly 29 hours (range 23—35 hours), which is similar to urine-derived hCG. After a single subcutaneous injection, roughly 10% of the dose is excreted unchanged in the urine within 24 hours.

    Intramuscular Route

    Urine-derived products: Urinary-derived human chorionic gonadotropin (hCG) is administered by the intramuscular (IM) route; however, one study has shown similar bioavailability with subcutaneous (SC) administration. Subjective observations in the literature have also supported the use of hCG by the SC route as equivalent to IM administration clinically. Serum concentrations of hCG are detectable within 2 hours of IM administration; peak concentrations are attained within 6 hours and persist for roughly 36 hours.

    Subcutaneous Route

    Urine-derived products: Urinary-derived human chorionic gonadotropin (hCG) is administered by the intramuscular (IM) route; however, one study has shown similar bioavailability with subcutaneous (SC) administration. Subjective observations in the literature have also supported the use of hCG by the subcutaneous (SC) route as equivalent to IM administration clinically.
    Recombinant hCG: Recombinant hCG (Ovidrel) is administered subcutaneously (SC). Following a 250 mcg SC dose, Cmax is achieved within 12—24 hours, with an absolute bioavailability of roughly 40%.