Gonadorelin, hCG, and Clomiphene: Which Is The Better Option?

GONADORELIN, HCG, AND CLOMIPHENE: WHICH IS THE BETTER OPTION?

Infertility affects one in every six couples who are trying to conceive. Contrary to popular belief, in at least half of all cases of infertility, a male factor is a major or contributing cause. This means that about 10% of all males in the United States who are attempting to conceive suffer from infertility. There is no gainsaying that infertility is a burning issue that is not gender specific. Fortunately, there are medicines that can help, such as Gonadorelin, hCG, and Clomiphene. To make an informed decision on which to go for, we will be discussing the three options in this blog post.

GONADORELIN

Gonadorelin, also referred to as gonadotropin-releasing hormone (GnRH), is frequently sold under the trade name Factrel. It is naturally released from the hypothalamus gland. Other hormones are released by the pituitary gland as a result of GnRH (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]). LH and FSH regulate fetal development and adult fertility. The hypothalamus and pituitary glands are tested with the drug gonadorelin. It is also used to induce ovulation in women who do not experience regular menstruation or ovulation because their hypothalamus gland does not emit enough GnRH.

HOW IS GONADORELIN USED?

According to your doctor’s instructions, gonadorelin is injected into a vein or beneath the skin using an infusion pump. Learn all preparation and usage instructions from your healthcare provider and the drug box if you’re using this medication at home. Utilize the infusion pump according to all directions. Before using the drug, do not combine it. Visually inspect the solution for particles or discoloration before administering this medication.

Use rubbing alcohol to disinfect the injection site before each dose. Change the injection location as instructed by your doctor if you are injecting the drug under the skin to reduce skin damage. Unless your doctor instructs you otherwise, you do not need to switch the injection site if you are injecting the drug into a vein.

SIDE EFFECTS OF GONADORELIN

Common side effects of Factrel (gonadorelin hydrochloride) include:

  • Headache
  • nausea
  • flushing
  • abdominal discomfort
  • lightheadedness
  • dizziness
  • skin rash, or
  • injection site reactions

Factrel may cause serious side effects, including:

  • hives,
  • swelling of your face, lips, tongue, or throat,
  • difficulty breathing,
  • flushing (continuing),
  • hardening of the skin at the place of injection,
  • rapid heartbeat,
  • itching, pain, redness or swelling of the skin at place of injection, and
  • skin rash

If you experience any of these side effects, you should contact your doctors immediately.

HUMAN CHORIONIC GONADOTROPIN (HCG)

A substance called human chorionic gonadotropin (hCG) is produced by trophoblast tissue, which is normally present in early embryos and will eventually make up the placenta. Because of its special function in sustaining a pregnancy, it is occasionally referred to as the pregnancy hormone. Around 10 to 11 days after pregnancy, HCG is detected in your urine or blood (when a sperm fertilizes an egg). The peak of your hCG levels (10 weeks into your pregnancy) is followed by a fall for the remainder of your pregnancy. To confirm pregnancy and provide information on how the pregnancy is developing, healthcare professionals measure hCG. Measuring hCG levels can be beneficial for determining if a pregnancy is healthy or pathologic, as well as for use after an abortion. It is used to alleviate issues with fertility after using menotropins to trigger the release of an egg (ovulation). Women whose ovaries are no longer producing eggs normally shouldn’t use it.

In order to induce the proper dropping of the testicles into the scrotum in males prior to puberty, human chorionic gonadotropin (hCG) is also employed. Additionally, it is utilized in some boys to support healthy sexual development. Male sex hormones (such as testosterone) are released from the testes as a result of it.

A number of diseases, including choriocarcinoma and extra-uterine malignancies, can also benefit from hCG measurement.

HOW TO USE HCG 

A medical expert will inject this drug into your muscle. Learn all of the preparation and usage guidelines for this product if you plan to administer this medication at home. Before using, visually inspect the product for any flecks or discoloration. The liquid should not be used if either is present. Consult your doctor or pharmacist if you have any questions regarding the administration of this drug.

Your age, weight, medical condition, and treatment response all factor into the dosage.

Use this medication as prescribed by your doctor for boys, often three times per week. Use this drug as directed for women, one dose once menotropin therapy is complete.

To reap the greatest benefits from this drug, take it frequently. Mark the day(s) on the calendar that you need to take the prescription to assist yourself in remembering.

SIDE EFFECTS OF HCG

There are some side effects of taking hCG, which may include:

  • Headache
  • Restlessness
  • Tiredness
  • Pain At Injection Site

Contact your doctor if you are experiencing any of these.

 CLOMIPHENE CITRATE

This drug is used to treat female infertility in patients. It functions by causing a rise in the hormones necessary to assist the development and release of a mature egg (ovulation). Women whose ovaries are no longer producing eggs adequately are not advised to take this medicine.

Additionally, because taking Clomid might boost testosterone and sperm count, it is frequently used off-label for the treatment of male infertility.

HOW TO USE CLOMIPHENE CITRATE 

For best results, clomiphene must be taken orally exactly as prescribed by your doctor. You should pay close attention to your dosing regimen.

Your medical condition and treatment response will determine your dosage. Never take it more frequently or for a longer period of time than your doctor has advised. It is not advised to use this drug for longer than six cycles at a time.

For the greatest outcomes, you could be told to take a body temperature reading, do ovulation tests, and time sexual encounters appropriately. In case you have any questions, consult your doctor.

SIDE EFFECTS 

Some of the side effects you may experience include:

  • Stomach upset
  • Bloating
  • Abdominal/pelvic
  • Fullness
  • Flushing (“hot flashes”)
  • Breast tenderness
  • Headache
  • dizziness may occur.

If any of these effects last or get worse, tell your doctor or pharmacist promptly.

GONADORELIN, HCG, AND CLOMIPHENE: WHICH IS THE BEST?

To really know which one of the three is the best, one must first evaluate the several studies that have been done. For instance, Turek, P.J. et al. study concluded that IM injections of HCG 2-3 times per week at doses of 2,000–3,000 IU for four months could initiate spermatogenesis after anabolic steroid-induced azoospermia. Also, it has been concluded by Coviello, A.D., et al., that a relatively low dose of hCG maintains ITT within the normal range in healthy men with gonadotropin suppression due to testosterone supplementation. Hsieh, T.C., et al., in another study, confirmed that intra-testicular testosterone could be maintained during testosterone replacement therapy with co-administration of low dose HCG, which may support continued spermatogenesis in patients on testosterone replacement therapy.

On the other hand, Habous M et al. conducted a study to compare serum testosterone response and symptom improvement in men with hypogonadism in response to treatment with clomiphene citrate (CC), human chorionic gonadotropin (hCG), or a combination of both therapies. It was concluded that all three treatments were equally effective in restoring testosterone levels. Single-agent CC is simple, cheap, and may be used as a treatment for hypogonadism when maintenance of fertility is desired. This approach seems to be as effective as either hCG alone or a combination of hCG and CC.

Also, Sinha S. & Agrawal N., in their study that compares the efficacy of sequential clomiphene citrate (CC) + Gonadotropin to that of Gonadotropin alone with ultrasound monitoring, concluded that there are significant differences in pregnancy rates and endometrial thickness were seen. Gonadotropin alone thus appears to give better results, but CC + Gonadotropin seems to be a cost-effective drug.

From all these studies, it is clear that all these medicines are effective for their own specific purpose. The only major differences are in their mode of administration (e.g Clomid is more effective when administered orally) and the side effects that occur from their intake.

The ultimate decision should be left to your doctors as they will know which suits your condition better. At HRT Doctors, we offer those three options in our male protocols. However, hCG is currently unavailable as it has been recently reclassified as a biologic by the (FDA). Once all pharmacies are re-certified to this new requirement, it will be made available again as an option.

HRT Doctors Group offers all 3 options as part of our male protocol TRT options.

REFERENCES

Center for Drug Evaluation and Research. (n.d.). Notice to compounders: Changes that affect compounding as of March 23. U.S. Food and Drug Administration. Retrieved September 6, 2022, from https://www.fda.gov/drugs/human-drug-compounding/notice-compounders-changes-affect-compounding-march-23-2020

Coviello, A.D., et al., Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced

Habous M, Giona S, Tealab A, Aziz M, Williamson B, Nassar M, Abdelrahman Z, Remeah A, Abdelkader M, Binsaleh S, Muir G. Clomiphene citrate and human chorionic gonadotropin are both effective in restoring testosterone in hypogonadism: a short-course randomized study. BJU Int. 2018 Nov;122(5):889-897. doi: 10.1111/bju.14401. Epub 2018 Jun 14. PMID: 29772111.

Hsieh, T.C., et al., Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol, 2013. 189(2): p. 647-50.

Sinha S, Agrawal N. Gonadotropin Alone is a Better Drug for Ovarian Stimulation than in Combination with Clomiphene in Intrauterine Insemination. J Obstet Gynaecol India. 2016 Oct;66(5):333-8. doi: 10.1007/s13224-015-0686-9. Epub 2015 Mar 13. PMID: 27486278; PMCID: PMC4958069.

Turek, P.J., et al., The reversibility of anabolic steroid-induced azoospermia. J Urol, 1995. 153(5): p. 1628-30.