Ganirelix Dosage

Ganirelix is ​​a well-known antagonist of the gonadotropin-releasing hormone (GnRH). This hormone regulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), both crucial in female reproductive health. Peptide blocks GnRH receptors, most notably in the anterior pituitary gland, and this prevents the release of these two hormones. This decapeptide contains several amino acids and is most commonly used in a medical procedure known as controlled ovarian hyperstimulation, which is intended to increase the chances of pregnancy. Scientists believe that due to the effects it has on the body, it could potentially be part of the treatment of polycystic ovary syndrome, endometriosis, and even benign tumors such as leiomyoma.

Dosage Chart

Timeline	Week 1-5	Week 6
Six-week protocol for increasing the chances of pregnancy research	0.25mg per day (one subcutaneous injection)	In some cases, the dose can be reduced (one subcutaneous injection)

 

About the Peptide

A crucial function of Ganirelix is ​​to block the GnRH receptor and thus suppress the release of two gonadotropins. FSH is crucial for developing follicles in the ovaries (formations that contain new eggs that should be released into the fallopian tube during ovulation and then fertilized). At the same time, LH is crucial for ovulation (the release of an egg, which occurs on the 14th day of the menstrual cycle).

Both hormones are essential for the process of fertilization and pregnancy. However, excessive secretion of LH leads to premature ovulation, which greatly reduces the chance of pregnancy, and can also initiate symptoms in polycystic ovary syndrome conditions such as high miscarriage rates, low pregnancy rates, cycle cancellation, and early ovulation. High LH levels are also associated with endometriosis and the development of certain benign tumors. We use this peptide to potentially restore hormone homeostasis and thus facilitate the process of conception and pregnancy, as well as a potential part of the therapy for mentioned diseases and conditions. The use of Ganirelix very rarely leads to any allergic reactions because its administration releases minimal histamine (the main mediator of inflammation).

The mechanism of action consists of modulating the hypothalamic-pituitary-gonadal system, blocking the receptor by competitive binding, which then leads to a profound but reversible suppression of the release of LH and FSH. Although the targeted effect is achieved in both gonadotropins, the suppression of LH release still has a significant and greater impact on the survival of pregnancy and conception. Unlike GnRH agonists, there is no initial rise in gonadotropin levels during administration of this peptide.

List of Uses for This Peptide

Impact of Peptide in Controlled Ovarian Hyperstimulation (COH)

Controlled ovarian hyperstimulation is a medical procedure that facilitates and assists the fertilization process and achieve pregnancy. This procedure uses hormone therapy in the form of medication to initiate ovulation. However, in this case, a larger number of egg follicles are created, and also cells that can be used later in the in vitro fertilization process. Superovulation may also occur when more eggs are released than usual (at least 2, instead of the regular 1).

This process can occur independently or as part of in vitro fertilization to achieve pregnancy. GnRH antagonists such as Ganirelix are also used in this procedure as part of the therapy to prevent early ovulation and premature maturation of follicles and egg cells because if this occurs, the chance of conception is greatly reduced. This peptide blocks GnRH receptors not only by competitive binding but also later transduction pathways. However, this process is reversible, which means that after achieving the desired result, the hormones return to their natural course.

The Connection between Ganirelix and Endometriosis

Endometriosis is a benign disease that is most often diagnosed in a woman's reproductive period, and it refers to the presence of endometrial tissue above the uterus, where it normally does not belong. The main symptoms include pain in the pelvis, extremely painful menstruation, and can even lead to infertility (scientists suspect that most of these symptoms are caused by increased levels of LH.) Some of the studies evaluated the effect of Ganirelix on the condition of endometriosis by assessing the main parameters before and after the administration of this peptide. Experimental animals (mice) were induced into this condition by transplanting endometrial tissues to the vascular surface. The results of the study indicate that Ganirelix could potentially cause changes in the expression of genes that are otherwise part of molecular mechanisms such as autophagy, which significantly improves and reduces symptoms in endometriosis conditions. The mechanism of action, as always, consists of the possibility of blocking GnRH receptors and preventing additional secretion, primarily of LH.

Ganirelix as a Potential Part of Leiomyoma Therapy

Uterine leiomyomas are benign tumors that usually affect older women. This tumor is most often localized on the body or cervix of the uterus and can arise from the uncontrolled proliferation of muscle or connective tissue. If the dimensions correspond to the surgical procedure, that is the most appropriate solution. However, scientists have assumed that GnRH antagonists may lead to cell death (in the form of apoptosis) and reduced extracellular synthesis in the tumor itself. Ganirelix was applied to leiomyoma tissue under controlled conditions, and the results showed that this peptide caused significant cell death in as much as 50-55%. In addition to tumor reduction, a reduced expression of certain factors that potentiate tumor progression was also observed. In such tumors, a disruption in hormone secretion is observed, primarily an increase in LH, while after the administration of the peptide, when the additional secretion of this gonadotropin is blocked, there is a potential reduction in tumor size and an improvement in the general condition. Such studies show that Ganirelix and other GnRH antagonists could potentially be part of the therapy in patients with uterine leiomyoma.

Potential Ganirelix Therapy in Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a condition that is currently a very common diagnosis in the younger population of women. In this syndrome, many microcysts form on the walls of the ovaries, which are associated with symptoms such as acne and insulin resistance. The crucial complication is difficulty conceiving. Patients with PCOS produce more follicles and eggs than healthy patients. The entire symptomatology is associated with a high dose of gonadotropin LH, and the therapy used so far has often led to an additional surge of this hormone. If there is a chronic increase in luteinizing hormone, ovarian hyperstimulation, multiple gestation, and even cycle cancellation can occur. The low pregnancy rate and high chance of miscarriage represent an additional problem. Ganirelix, as one of the GnRH antagonists, managed to suppress LH levels in all patients with just one dose at the recommended dosage. All patients included in the study achieved ovulation at the expected time, and a balance of hormones and gonadotropins was achieved. The pregnancy rate increased significantly, and the percentage of spontaneous abortions was reduced, as shown by the results of this and various other studies. According to this, Ganirelix could potentially be part of the therapy in the case of polycystic ovary syndrome.

Dosage Calculator

As mentioned above, Ganirelix is ​​a GnRH antagonist, so the use of this peptide is a hormonal treatment, which means that dosage is crucial to avoid unwanted effects. The peptide is recommended at a dose of 250 mcg/0.5L subcutaneously by injection once a day. If used in combination with human chorionic gonadotropin (hCG), it is used until the day of administration of this hormone. Ganirelix can be ​​used for a medical procedure known as controlled ovarian hyperstimulation, which is also its most common use. In such a case, the dosage remains the same, but the period of administration differs. Studies investigating the best way to perform this medical procedure lasted an average of 6 weeks, where the peptide was administered at a fixed dose of 250 mcg/0.5L per day for the first 5 weeks. In the sixth week the dose could be reduced if necessary, but the method of administration remained the same, subcutaneous in the form of one injection per day. The recommended daily dose must not be exceeded and is intended for adults.

Conclusion

Ganirelix is ​​a GnRH antagonist whose primary function is to reduce the secretion of FSH and LH, upon which all other functions and roles of the peptide are based. When used at the recommended dose of 250 mcg/0.5L for adults, potential beneficial properties are expected. Its primary application is in controlled ovarian hyperstimulation, but it is also used in conditions such as endometriosis, polycystic ovary syndrome, or tumors such as leiomyomas. In these patients, ganirelix reduces the LH increase, stabilizes the hormonal status, and thus increases the chance of pregnancy. Ganirelix will certainly be the subject of research in the future.

References:

1. B. Mannaerts, P. Devroey, T. Åbyholm, K. Diedrich, D. de Jong, … The Ganirelix Dose‑Finding Study Group, “A multicentre, double‑blind, randomized dose‑finding study of Org 37462 (ganirelix) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle‑stimulating hormone (Puregon®),” Human Reproduction, vol. 13, no. 11, pp. 3023–3031, Nov. 1998, doi: 10.1093/humrep/13.11.3023.
2. M. W. Jurema, “Beneficial use of ganirelix in controlled ovarian …” [abstract], Fertility and Sterility, 2001; daily ganirelix (0.25 mg SQ) administered once leading follicle reached diameter of 14 mm or when serum LH > 10 mIU.
3. European Orgalutran® Study Group, “Treatment with the gonadotrophin‑releasing hormone antagonist ganirelix (0.25 mg daily) prevented LH from rising above 10 IU L⁻¹ during stimulation, with good clinical outcome,” Hum. Reprod., vol. 15, no. 7, pp. 1490–1490 (abstr.), 2000.
4. A. B. Copperman, “Optimal usage of the GnRH antagonists: a review of the dosing schedules,” Reproductive Biology and Endocrinology, vol. 11:20, 2013, doi: 10.1186/1477‑7827‑11‑20.
5. C. Westergaard, E. Laursen, J. Andersen, A. Petersen, … The Scandinavian Study Group, “Comparison of the GnRH antagonist ganirelix and the GnRH agonist buserelin in assisted reproduction: a randomized clinical trial,” Human Reproduction, vol. 16, no. 4, pp. 644–651, Apr. 2001, doi: 10.1093/humrep/16.4.644.
6. T. Olivennes, P. Fanchin, R. Bouchard, P. Taieb, … R. Frydman, “The use of a GnRH antagonist (ganirelix) in patients with endometriosis undergoing ovarian stimulation: preliminary results,” Human Reproduction, vol. 14, suppl. 2, pp. 72–77, 1999, doi: 10.1093/humrep/14.suppl_2.72.
7. J. Shah, A. Edelstein, S. Kumar, L. Sauerbrun-Cheor, … R. Reindollar, “Suppression of luteinizing hormone with ganirelix improves outcome in women with leiomyomas: a pilot study,” Reproductive Biomedicine Online, vol. 17, no. 2, pp. 246–252, Aug. 2008, doi: 10.1016/S1472-6483(10)60203-2.