Potential of Gonadorelin in Cancer and Reproductive Health

Gonadorelin is a synthetic peptide possessing ten amino acids, and all are joined in a sequential form.⁽¹⁾ Structurally like the endogenous GnRH, Gonadorelin has 1-2 amino acid changes within the sequence.⁽²⁾ Identical to the naturally present GnRH hormones, Gonadorelin is a peptide with the potential to act as a GnRH agonist and regulate gonadotropin levels in the body.

Gonadorelin peptide has the potential to stimulate the anterior pituitary gland and increase the synthesis and release of gonadotropins, FSH, and LH, in the body.⁽³⁾ This is primarily why they are called GnRH agonists, as they produce the same effect as GnRH.

That said, when administered at high and sustained doses, Gonadorelin peptide may also downregulate the GnRH receptors located in the pituitary gland. This peptide hormone may bind to the receptors, stimulating the gonadotropins’ secretion. Over time, the receptors become less sensitive towards this peptide, causing downregulation of the receptors, thereby reversibly inhibiting the release of LH and FSH.

Gonadorelin Peptide Research

Studies suggest that administration of the Gonadorelin peptide for 10 years reduces the risk of breast cancer by 50%, and when used for 15 years, the risk is reduced by 70%.⁽⁴⁾ Gonadorelin peptides have the potential to block the effects of mitogens estrogen and progesterone, reduce breast cell exposure to these mitogens, and act as a preventative agent against breast cancer.

Furthermore, studies⁽⁵⁾ have suggested that gonadotropin-releasing hormone analogs, such as Gonadorelin, may be safe for postmenopausal women at increased risk of breast cancer. Postmenopausal women who suffer from ovarian hyperandrogenemia, i.e., excessive androgen synthesis, are at a greater risk of breast cancer. Per Secretio G et al.:

“The postmenopausal ovary is an important source of excessive androgen production, which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.” ⁽⁵⁾

Gonadorelin peptides may also have preventative effects on the development of cancer cells in the prostate. GnRH analogs such as Gonadorelin peptide have the potential to inhibit the synthesis of Luteinizing hormones due to the decreased sensitivity of the GnRH receptors, which causes a decline in testosterone and dihydrotestosterone production. The development of prostate cancer cells is directly proportionate to these testosterone levels; therefore, this cancer may be effectively inhibited through GnRH analogs.

Administering these analogs with radiotherapy or chemotherapy may also help treat highly progressive cancer patients. 

• Gonadorelin peptide demonstrates potential in suppressing Spermatogenesis and Gonadotropins.
• Studies⁽⁵⁾have suggested that GnRH analogs such as Gonadorelin peptide may reduce sperm count, potentially azoospermia, in all men. Upon administration, the average sperm count appeared reduced by 93% in all candidates, also causing azoospermia in three of the seven men participating in the study. The complete absence of sperms in the ejaculate characterizes azoospermia.
• Research⁽⁶⁾ has suggested that sex hormones, specifically the Luteinizing hormone, act on the brain, mainly the hippocampus, which is the brain’s memory center and causes dysfunction. This dysfunction includes decreased memory performance, thereby inducing dementia and Alzheimer’s. To prevent the occurrence of dementia, the synthesis and secretion of luteinizing hormone (LH) need to be blocked, and this can potentially be achieved by GnRH analogs such as Gonadorelin peptide.
• Gonadorelin peptide is a promising complement to the diagnostic tests for determining the functioning of the gonadal axis.
• Research indicates that the pituitary secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by Gonadorelin peptide may not depend on the concentration of these hormones; instead, it may depend on the proper working of the hypothalamic and pituitary axis. The greater the severity of the improper functioning of the hypothalamic and pituitary axis, the higher the secretion of the gonadotropins.
• Gonadorelin peptide is also being evaluated for its potential use in treating ovarian cancer and osteoporosis in women.

Gonadorelin Safety Profile

The reported side effects caused by administration of the peptide has been reported in some research studies to include:

• Headaches
• Nausea
• Abdominal pain
• Flushing
• Lightheadedness
• Rashes
• Redness, pain, and swelling at the site of administration

Avoid using Gonadorelin peptide in the presence of the following medical problems in test subjects:⁽⁷⁾

• Gonadotropin-releasing hormone adenoma: This condition is characterized by non-carcinogenic tumors. This is a sporadic condition; however, it is crucial to monitor Gonadorelin peptide administration, as it may lead to sudden loss of eyesight.
• Presence of hormone-dependent tumors: Gonadorelin peptide must be avoided as it may lead to androgens production, and this increased presence of androgens in the body can worsen the condition.

Gonadorelin peptide has a short distribution half-life of 2 to 10 minutes – meaning it starts showing its effects within 10 minutes. The peptide is believed to undergo hydrolysis by certain endogenous enzymes and is then broken down into short inactive peptide components. This hydrolysis of the peptide occurs within 40 minutes of administration.⁽⁸⁾

Conclusion

Gonadorelin is a decapeptide, a gonadotropin-releasing hormone (GnRH) agonist. It has the potential to equilibrate the levels of gonadotropin luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the body.

Gonadorelin peptide may help regulate LH and FSH synthesis and release levels by acting on the GnRH receptors located in the pituitary gland. Gonadorelin is being studied for its potential to treat breast and prostate cancer and is undergoing evaluation for its therapeutic effects in osteoporosis, Alzheimer’s, dementia, and ovarian and prostate cancer.

This peptide is strictly available for research and laboratory settings, not personal use.

References:

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 638793, Gonadorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Gonadorelin.
2. Philip GA Thomas, Alain Fontbonne, Drugs and reproduction. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/gonadorelin-acetate
3. Lepor, Herbert. “Comparison of single-agent androgen suppression for advanced prostate cancer.” Reviews in urology vol. 7 Suppl 5, Suppl 5 (2005): S3-S12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477619/
4. Secreto G, Sieri S, Agnoli C, Grioni S, Muti P, Zumoff B, Sant M, Meneghini E, Krogh V. A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women. Breast Cancer Res Treat. 2016 Aug;158(3):553-61. https://pubmed.ncbi.nlm.nih.gov/27393623/
5.  Bhasin S, Yuan QX, Steiner BS, Swerdloff RS. Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist in men: effects of long term treatment with GnRH agonist infusion and androgen. J Clin Endocrinol Metab. 1987 Sep;65(3):568-74. https://pubmed.ncbi.nlm.nih.gov/3114307/
6. Rao CV. Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women. Reprod Sci. 2017 Mar;24(3):355-368. https://pubmed.ncbi.nlm.nih.gov/27436369/
7. Gonadorelin (Intravenous Route, Injection Route). https://www.mayoclinic.org/drugs-supplements/gonadorelin-intravenous-route-injection-route/description/drg-20067426
8. Gonadorelin. https://go.drugbank.com/drugs/DB00644

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