What is Compounded HCG?

What is HCG?

The hCG is a short term for human chorionic gonadotropin that is a glycopeptide composed of 237 amino acids in the same family as follicle stimulating hormone (FSH) and luteinizing hormone (LH) [5]. hCG is produced from cyptotrophoblast during early pregnancy. The aim of hCG therapy is to utilize the endogenous hormonal (gonadotropin) function of LH and FSH.

The gonadotropin hormones (hCG, FSH, and LH) are highly glycosylated and exist as heterodimer of α:β in which the α subunit is identical within these glycopeptides while the β subunit is different in each gonadotropin hormone that determines their functional effect.

Due to a presence of homology between the hCG and LH hormones, the hCG can be used to assist the reproduction by mimicking the mid-cycle of LH surge. In spite of their similar structure, they also share the same receptor, LH/CGR. However, hCG can be distinguished from LH due to its longer half-life and higher affinity for LH/CGR receptor, which makes the hCG more potent than LH.

History and Background of HCG

During 1927, Ascheim and Zondek demonstrated that the blood and urine of the pregnant women has a gonad-stimulating substance [1]. Thus, they injected this substance subcutaneously in immature female mice and observed the production of follicular maturation, luteinizaton and haemorraghe into ovarian stroma, which this then became the Ascheim Zondek pregnancy test. They thought that is substance is produced by anterior pituitary gland while Seeger-Jones showed that this gonadotropin was produced in vitro in placental tissue.

The gonadotrophic hormone hCG was described to be very similar to pituitary hormone ‘Prolan B’ (LH) as mentioned by Marius Tausk’s book history of Organon. In 1931, Tausk launched this extract on the market under the name of ‘Pregnon’. However, due the similarity with another trademark, the name was changed to ‘Pregnyl’. Then, Pregnyl was released in 1932, when the regulatory authorities for evaluation and approval of the medicine did not exists yet, and it exists until the present day.

Later in 1939, urine-based hCG harvested from the urine of a pregnant woman was approved by FDA. During 2000, the first recombinant hCG under the name, Ovidrel, was approved by FDA, which was indicated for female fertility with main function of triggering final step of maturation of follicles.

What is a Troche?

Troche is a small type of medicated lozenge that gets dissolved between the cheeks and gum roughly between eight to thirty minutes. Troches have been used since the 1800s, but recently, they have gained popularity over other dosage forms due to a fast absorption and the reduction of first pass metabolism.  This makes it a convenient sublingual or transmucosal dosage form for a select patient population[6].

HCG in Troches

hCG in Troches have a greater tendency to get absorbed directly into bloodstream and with a decreased passage through the liver.  Since hCG is naturally produced in humans, the body can quickly recognize, utilize, metabolize and excrete it.


Therapeutic Use of HCG

Oocyte maturation and ovulation need mid-cycle LH surge in which purified hCG has been used for decades as a surrogate for LH to achieve the final process of oocyte maturation and ovulation [3]. For that reason, urinary hCG has been the drug of choice; however, other options exists as recombinant LH (rLH) and recombinant hCG (rhCG).

The rhCG is another form of therapeutic hCG, which has been commercially available by recombinant techniques in Chinese hamster ovary cells.

Mechanism of Action

Primarily, chorionic gonadotropin exerts its action on ovaries and testes [3]. In ovaries, hCG works with follicle stimulating hormone to produce a mature ovum and triggers corpus luteum to produce progesterone. In testicles, it induces the production of androgen leading to the development of secondary sex characteristics and production of testosterone and may stimulate testicular descent if there are not anatomical abnormalities.

Place in Therapy

  • FDA USE:
  • Cryptorchidism
  • Hormonal therapy has been used in the United States for treatment of cryptorchidism because it induces the testicular descent. While, the rational behind it is being that endorcrine factors, and specifically disorders of hypothalamic-pituitary-gonadal axis, likely play a role in cryptorchidism. hCG is part of the HPG axis that stimulates production of androgen by Leydig cells, which mimics the function of pituitary LH.  Then, androgen stimulation in male leads to the development of secondary sex characteristics and may stimulate testicular descent.
  • Hypogonadotropic hypogonadism, In male patients
  • Ovulation Induction
  • LH’s function is development and maturation of ovarian follicle, and the mid-cycle LH surge triggers ovulation. hCG can substitute for LH in this function.
  • Non-FDA USE
  • Erectile dysfunction
  • Female infertility therapy, Luteal phase support
  • Hypospadias
  • Kaposi's sarcoma
  • Obesity [3]

HCG-Based Combination Therapy with Supplemental Testosterone:

The use of supplemental testosterone among men of reproductive years has increased and became quite common. However, these men are unaware that exogenous testosterone diminishes spermatogenesis through negative feedback mechanism in the hypothalamus-pituitary-gonadal axis by decreasing the release of FSH and LH, which leads to decreased production of Leydig cells and testosterone that reduces the coupling with Sertoli cells and thus, diminished spermatogenesis. While, addition of HCG can reduce the testosterone supplemental therapy (TST)-induced infertility as it can raise the serum and intratesticular testosterone levels that are essential for normal spermatogenesis.

According to “The Use of HCG-Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use”, HCG-based therapy with testosterone supplements such as clomiphene citrate, tamoxifen, or anastrazole demonstrated quick restoration of spermatogenesis in individuals with TST-induced infertility.

* Evan Wenker, The journal of sexual medicine’ 2015

Adverse Effects

  • Most Common:
  • Dermatologic: Injection site pain
  • Endocrine metabolic: Gynecomastia, Precocious puberty
  • Neurologic: Headache
  • Psychiatric: Depression, Irritability, Restlessness
  • Serious:
  • Cardiovascular: Arterial thromboembolism
  • Hepatic: Ascites
  • Immunologic: Anaphylaxis
  • Reproductive: Ovarian hyperstimulation syndrome
  • Respiratory: Pleural effusion


  • Precoccious puberty: when puberty begins too soon.
  • During pregnancy may cause fetal harm, pregnancy category C
  • Prostate cancer and other androgen-dependent neoplasm
  • Prior allergic reactions to hCG

  • Monitoring

    After use of hCG, it’s recommended to check the serum level of progesterone, luteinizing hormone (LH), and estradiol. Also, it is recommended to get an ovarian ultrasound day 7 and 14 of hCG use for women as well as routine pelvic exam. If hCG is used for the treatment of cryptorchidism, it is essential to look for the signs of precocious puberty and if detected one, then should contact primary care physician.



    Bruno Lunenfeld; Historical perspectives in gonadotrophin therapy, Human Reproduction Update, Volume 10, Issue 6, 1 December 2004, Pages 453–467, https://doi.org/10.1093/humupd/dmh044


    Chroionic Gonadotropin. APP Pharmaceuticals, LLC, Jan. 2008, www.meritpharm.com/wp-content/uploads/2014/03/Chorionic.Insert.APP_.pdf.


    Chorionic Gonadotropin. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at:  https://www-thomsonhc-com.ezproxy.cnsu.edu/micromedex2/librarian/CS/3B8D71/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/71EC31/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.IntermediateToDocumentLink?docId=261025&contentSetId=100&title=Chorionic+Gonadotropin&servicesTitle=Chorionic+Gonadotropin#close. Accessed September 15, 2018.


    Kurz, David. “Current Management of Undescended Testes.” Current treatment options in pediatrics 2.1 (2016): 43–51. PMC. Web. 15 Sept. 2018


    Theofanakis, Charalampos et al. “Human Chorionic Gonadotropin: The Pregnancy Hormone and More.” Ed. Udo Jeschke. International Journal of Molecular Sciences 18.5 (2017): 1059. PMC. Web. 14 Sept. 2018.


    “What Is a Troche?” O'Brien Pharmacy, O'Brien Pharmacy, obrienrx.com/troche/.


    Wenker, Evan P., et al. "The use of HCGbased combination therapy for recovery of spermatogenesis after testosterone use." The journal of sexual medicine 12.6 (2015): 1334-1337.