HCG Injection

Human Chorionic Gonadotropin (HCG) Injection is a sterile preparation of human chorionic gonadotropin, supplied as a lyophilized powder (10,000 IU) for reconstitution.^[1] HCG is a polypeptide hormone produced by the human placenta; it shares an alpha subunit with pituitary luteinizing hormone (LH) but has a distinct beta subunit that confers its specific activity.^[2] This HCG Injection is the branded product Pregnyl, formulated in a buffered powder to be mixed with diluent before use. It is FDA-approved for various clinical indications. HCG Injection is available by prescription only and intended for use under medical supervision. FDA-approved preparations of chorionic gonadotropin include Pregnyl and Novarel (urine-derived HCG for intramuscular use) and Ovidrel (recombinant HCG for subcutaneous use).

HCG Injection is used for its gonadotropic properties in certain reproductive and endocrine disorders. In women, HCG is used to induce ovulation and support early pregnancy as part of infertility treatment protocols (for example, as an ovulation “trigger” in anovulatory women or those undergoing assisted reproductive technologies). In men, HCG is employed to stimulate testosterone production and spermatogenesis in hypogonadotropic hypogonadism (secondary hypogonadism due to pituitary deficiency). It can help increase sperm counts and restore fertility in some men by mimicking the action of LH on the testes. HCG is also indicated for prepubertal cryptorchidism (undescended testicles) in young boys when the cause is not anatomical, in order to promote testicular descent prior to puberty. By acting like LH, HCG can spur the testes to produce androgens that facilitate testicular descent and the development of secondary sexual characteristics. Other less common uses of HCG include certain diagnostic tests in endocrinology (HCG stimulation tests) and off-label use to maintain intratesticular testosterone levels in men on exogenous testosterone therapy, though such uses must be guided by a physician.^[3]

Importantly, HCG is not a weight-loss medication. Studies have conclusively shown that HCG injections do not aid in fat loss or appetite suppression beyond the effects of calorie restriction alone. There is no substantial evidence that HCG causes any more weight loss, fat redistribution, or hunger reduction than diet alone.^[4][5] Any use of HCG for weight management (the basis of the disproven “HCG diet”) is not supported by medical science and is considered ineffective and unsafe. Therefore, HCG Injection should only be used for its established fertility and endocrine indications, and patients should be wary of products or programs that claim weight-loss benefits from HCG.

HCG exerts its effects by binding to luteinizing hormone (LH) receptors on target cells in the ovaries and testes, thereby mimicking the action of endogenous LH. In the ovaries, an injection of HCG essentially substitutes for the natural LH surge, triggering the final maturation of the ovarian follicle and the release of the egg (ovulation). After ovulation, HCG supports the corpus luteum so it continues to produce progesterone and estrogen – hormones necessary to maintain the uterine lining for implantation and early pregnancy. In this way, HCG fosters the hormonal conditions needed for the establishment of pregnancy. In the testes, HCG stimulates the interstitial Leydig cells to produce androgens (primarily testosterone), just as LH would. The increase in testosterone can promote the development of secondary sexual characteristics and, in conjunction with follicle-stimulating hormone (FSH), support spermatogenesis. In young males with cryptorchidism, this testosterone surge can sometimes induce the descent of the testes into the scrotum (if no anatomical impediment exists).^[6]

By acting as an LH analog, HCG activates the same cellular signaling pathways (cAMP-mediated) that lead to steroid hormone production in the gonads.^[6] This mechanism of action underlies its clinical uses: it induces ovulation in women who need assistance conceiving, and it stimulates testosterone production in men who have functional testes but inadequate pituitary stimulation. HCG’s effects are specific to functional gonadal tissue – it will not be effective in cases of primary ovarian failure or primary testicular failure where the glands cannot respond. In summary, HCG “stands in” for LH, causing the gonads to produce sex steroids and gametes (eggs or sperm) as needed for fertility.

HCG Injection is contraindicated in patients with known hypersensitivity to HCG or any component of the formulation.^[7] It should not be used in individuals with hormone-sensitive tumors, such as prostate cancer or breast cancer, due to the risk of stimulating tumor growth through increased androgen or estrogen production. Additionally, HCG is contraindicated in cases of precocious puberty, as it may exacerbate early sexual development, especially in prepubertal males receiving it for cryptorchidism.^[8][9]

HCG is classified as a Category X drug for pregnancy, meaning it should not be used by women who are pregnant or planning to become pregnant during treatment.^[10] Its administration during pregnancy carries potential risks to fetal development, and it is not indicated for use once pregnancy is confirmed. Women of childbearing age should use effective contraception during treatment and discontinue the medication if pregnancy occurs.

Caution is also advised in patients with conditions such as asthma, cardiac disease, renal impairment, migraine, or epilepsy, as HCG can lead to fluid retention that may worsen these conditions. Individuals with a history of thromboembolic disorders should also be carefully evaluated prior to treatment, especially when HCG is used as part of ovulation induction protocols in women, as it may increase thrombotic risk through hormone elevation.^[11][13]

There are limited known drug–drug interactions with HCG. However, its endocrine effects may influence the action or monitoring of certain medications. For example, concurrent use with corticosteroids may amplify the potential for fluid retention or electrolyte imbalance, particularly sodium and water retention. HCG can theoretically counteract the effects of anticoagulants or increase the risk of thrombosis when combined with estrogen-containing therapies or ovulation induction protocols in women.^[14][15]

HCG may also interfere with diagnostic tests. Notably, it can lead to a false-positive pregnancy test due to its molecular similarity to endogenous pregnancy HCG, which is the target of standard hCG immunoassays.^[16] Elevated levels following injection may persist for up to two weeks and should be considered when interpreting test results. Cross-reactivity with other hormone assays, particularly LH, can also occur, potentially affecting evaluations of gonadotropin levels during treatment.

When HCG is administered alongside other fertility treatments, such as clomiphene citrate or menotropins, the risk of ovarian hyperstimulation syndrome (OHSS) increases, requiring careful monitoring by reproductive specialists.^[17] Any additional hormonal or pituitary-modulating agents should only be used with HCG under medical supervision due to the potential for complex endocrine interactions.

Common side effects of HCG Injection include localized injection site reactions such as pain, redness, and swelling, which are usually mild and transient.^[18] Systemic side effects may include headache, irritability, restlessness, depression, fatigue, or edema resulting from fluid retention. These effects are typically dose-dependent and reversible upon discontinuation.^[18][19]

In males, prolonged HCG use may lead to gynecomastia due to increased aromatization of testosterone to estradiol. Other androgenic side effects include acne, oily skin, and mood fluctuations. In pediatric patients receiving HCG for cryptorchidism, early onset of puberty (precocious puberty) has been reported in rare cases.^[20]

Serious adverse effects are uncommon but may include allergic reactions, such as rash, hives, or anaphylaxis, especially in individuals sensitive to urinary-derived HCG products. In women undergoing fertility treatments, a potentially life-threatening complication is ovarian hyperstimulation syndrome (OHSS), characterized by rapid weight gain, abdominal pain, ascites, and electrolyte imbalances. Prompt medical evaluation is necessary if such symptoms occur.^[21][22]

HCG should not be used during pregnancy, as it is classified as FDA Pregnancy Category X.^[23] The hormone has no role in pregnancy maintenance once implantation has occurred, and exogenous administration poses a risk of endocrine disruption or fetal effects. There is no clinical benefit and potential for harm if administered during gestation. Women who become pregnant while receiving HCG should discontinue its use immediately and consult their physician.

While it is not known whether HCG is excreted in human milk, caution is recommended for nursing mothers.^[24] Due to its hormonal activity and lack of safety data, breastfeeding during treatment with HCG is not advised. Healthcare providers should evaluate risks and benefits individually when advising postpartum patients.

Unreconstituted HCG vials should be stored at controlled room temperature (15–30°C) and protected from light and moisture. After reconstitution with bacteriostatic water, the solution should be refrigerated (2–8°C) and used within 30 to 60 days depending on the manufacturer (refer to the label of the medication).^[29][30] Vials should not be frozen, and any cloudy or particulate solution should be discarded.

Proper disposal of expired or unused medication is critical. Patients should return unused vials to the pharmacy or follow local disposal protocols. Keep all medications out of reach of children.

1. Organon. (2011). Pregnyl (chorionic gonadotropin for injection, USP) [Prescribing Information]. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018216s031lbl.pdf
2. MedlinePlus. (2022, December 12). Chorionic gonadotropin injection. U.S. National Library of Medicine. Retrieved from https://medlineplus.gov/druginfo/meds/a682335.html
3. American Society for Reproductive Medicine. (2015). Optimizing natural fertility: A committee opinion. Fertility and Sterility, 103(3), 522–528. https://doi.org/10.1016/j.fertnstert.2014.12.033
4. Lijesen, G. K., Theeuwes, J. W., Assendelft, W. J., Van Der Wal, G., & Ferrier, M. B. (1995). The effect of HCG in the treatment of obesity by means of the Simeons therapy: A criteria-based meta-analysis. British Journal of Clinical Pharmacology, 40(3), 237–243. https://doi.org/10.1111/j.1365-2125.1995.tb05790.x
5. National Institutes of Health. (2021). HCG diet: Is it safe and effective? National Center for Complementary and Integrative Health. Retrieved from https://nccih.nih.gov/news/hcg-diet
6. Hoffman, B. L., Schorge, J. O., Schaffer, J. I., Halvorson, L. M., Bradshaw, K. D., & Cunningham, F. G. (2020). Williams gynecology (4th ed.). McGraw-Hill Education.
7. DailyMed. (2022). Chorionic gonadotropin (HCG) injection [Label information]. National Library of Medicine. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b9fc5af3-5a9e-472e-a9cc-2032deab80e6
8. Mayo Clinic. (2021). Prostate cancer: Causes, symptoms, and diagnosis. Mayo Foundation for Medical Education and Research. Retrieved from https://www.mayoclinic.org/diseases-conditions/prostate-cancer
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10. Briggs, G. G., Freeman, R. K., & Yaffe, S. J. (2017). Drugs in pregnancy and lactation: A reference guide to fetal and neonatal risk (11th ed.). Wolters Kluwer.
11. American College of Obstetricians and Gynecologists. (2017). Thromboembolism in pregnancy. Practice Bulletin, 196, 1–18. https://doi.org/10.1097/AOG.0000000000002257
12. Goldstein, D. J. (1999). Beneficial effects of HCG therapy on migraine and fluid balance. Journal of Clinical Endocrinology & Metabolism, 84(6), 2050–2055. https://doi.org/10.1210/jcem.84.6.5766
13. Schally, A. V., & Arimura, A. (1975). Hypothalamic regulation of the pituitary hormones. Annual Review of Physiology, 37, 379–408. https://doi.org/10.1146/annurev.ph.37.030175.002115
14. Lexicomp. (2023). HCG drug monograph. Wolters Kluwer Health, Inc.
15. Speroff, L., & Fritz, M. A. (2005). Clinical gynecologic endocrinology and infertility (7th ed.). Lippincott Williams & Wilkins.
16. Sturgeon, C. M., & Viljoen, A. (2011). Analytical error and interference in immunoassay: minimizing risk. Annals of Clinical Biochemistry, 48(5), 418–432. https://doi.org/10.1258/acb.2011.011062
17. Practice Committee of the American Society for Reproductive Medicine. (2016). Use of exogenous gonadotropins for ovulation induction in anovulatory women: A committee opinion. Fertility and Sterility, 106(7), e94–e99. https://doi.org/10.1016/j.fertnstert.2016.09.040
18. FDA Adverse Event Reporting System. (2022). Chorionic gonadotropin: Adverse effects database. U.S. Food and Drug Administration.
19. WebMD. (2023). HCG (human chorionic gonadotropin) side effects. Retrieved from https://www.webmd.com/drugs/2/drug-15717/hcg-intramuscular/details
20. Reiter, E. O., & Fuld, K. (2006). Precocious puberty and related disorders. Journal of Clinical Endocrinology & Metabolism, 91(9), 3854–3859. https://doi.org/10.1210/jc.2006-0509
21. Drugs..com. (2023). HCG side effects. Retrieved from https://www.drugs.com/sfx/hcg-side-effects.html
22. Practice Committee of the ASRM. (2016). Ovarian hyperstimulation syndrome (OHSS). Fertility and Sterility, 106(7), e251–e256. https://doi.org/10.1016/j.fertnstert.2016.08.048
23. U.S. FDA. (2018). Pregnancy and lactation labeling (Drugs). Retrieved from https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs
24. Hale, T. W. (2019). Medications and mothers’ milk (18th ed.). Springer Publishing.
25. Empower Pharmacy. (2024). HCG injection instructions: Reconstitution and administration guidelines. Internal publication.
26. NICE. (2017). Fertility problems: Assessment and treatment. Clinical guideline [CG156]. National Institute for Health and Care Excellence.
27. World Health Organization. (2012). Guidelines on the diagnosis and treatment of male infertility. WHO Press.
28. Zitzmann, M., & Nieschlag, E. (2000). Hormone treatment in male hypogonadism. Endocrine Reviews, 21(5), 579–607. https://doi.org/10.1210/edrv.21.5.0409
29. U.S. Pharmacopeial Convention. (2022). USP : Pharmaceutical compounding –Sterile preparations. United States Pharmacopeia and National Formulary.
30. Medisca. (2023). Stability data for reconstituted lyophilized peptides. Technical bulletin.