The characteristics of pharmacokinetics and the biological effects of gonadotropin-releasing hormone agonists
This paper presents a literature review of the physiological and pharmacokinetic features of used gonadotropin-releasing hormone (GnRH) agonists. It considers in detail the mechanism of action of drugs of this group at the level of receptors, as well as their mediated physiological effects. GnRH agonists initially stimulate and then inhibit sex hormone secretion by desensitizing pituitary GnRH receptors. There are examples of the clinical use of GnRH agonists. The latter are used to treat hormone-dependent diseases, such as endometriosis, uterine leiomyoma, pubertas precox, breast cancer, as well as in assisted reproductive technology protocols. Decreased bone mineralization due to hypoestrogenism is known to be one of the extremely negative effects of long-term use of GnRH agonists. The article discusses the ways of reducing the frequency and severity of GnRH side effects, including add-back therapy or changing the regimen of prescribing GnRH agonists.Rukhlyada N.N., Biryukova E.I.
Conclusion: The introduction of GnRH agonists was another breakthrough in gynecological practice and made it possible to successfully overcome previously unsolvable problems, such as infertility, severe endometriosis. Further joint developments by physiologists, biochemists, and clinicians suggest the increase in the efficacy of drugs and the expansion of their therapeutic abilities while reducing the risks of their use.
Authors’ contributions: Rukhlyada N.N., Biryukova E.I. – concept and design of the investigation, material collection and processing, selection of literature on the stated topic, writing the text, editing.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: This investigation has not been sponsored.
For citation: Rukhlyada N.N., Biryukova E.I. The characteristics of pharmacokinetics and
the biological effects of gonadotropin-releasing hormone agonists.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023;(2): 154-158 (in Russian)
https://dx.doi.org/10.18565/aig.2023.42
Keywords
gonadotropin-releasing hormone (GnRH)
GnRH agonists
GnRH receptors
References
- Esencan E., Taylor H.S. Gonadotropin-releasing hormone antagonists revolutionizing gynecology. Obstet. Gynecol. 2022; 140(6): 917-9.https://dx.doi.org/10.1097/AOG.0000000000005012.
- Knobil E. The neuroendocrine control of menstrual cycle. Recent. Prog. Horm. Res. 1980; 36: 53-88. https://dx.doi.org/10.1016/b978-0-12-571136-4.50008-5.
- Tzoupis H., Nteli A., Androutsou M.E., Tselios T. Gonadotropin-releasing hormone and GnRH receptor: structure, function and drug development. Curr. Med. Chem. 2020; 27(36): 6136-58. https://dx.doi.org/10.2174/0929867326666190712165444.
- Бурлев B.A., Кузьмичев Л.Н., Онищенко A.C., Ильясова Н.А., Щетинина Н.С. Функциональная активность эндометрия влияет на результаты ЭКО и перенос эмбрионов: молекулярные механизмы регуляции фертильности. Проблемы репродукции. 2010; 16(2): 41-52. [Burlev V.A., Kuz'michev L.N., Onishchenko A.C., Il'iasova N.A., Shchetinina N.C. Endometrial functional activity and the results of IVF: molecular mechanisms. Russian Journal of Human Reproduction. 2010; 16(2): 41-52. (in Russian)].
- Newton C.L., Riekert C., Millar R.P. Gonadotropin-releasing hormone analog therapeutics. Minerva Ginecol. 2018; 70(5): 497-515.https://dx.doi.org/10.23736/S0026-4784.18.04316-2.
- Pratap A., Garner K.L., Voliotis M., Tsaneva-Atanasova K., McArdle C.A. Mathematical modeling of gonadotropin-releasing hormone signaling. Mol. Cell. Endocrinol. 2017; 449: 42-55. https://dx.doi.org/10.1016/j.mce.2016.08.022.
- Tavaniotou A., Smitz J., Bourgain С., Devroey P. Ovulation induction disrupts phase function. Ann. N. Y. Acad. Sci. 2001; 943: 55-63.https://dx.doi.org/10.1111/j.1749-6632.2001.tb03790.x.
- Voliotis M., Garner K.L., Alobaid H., Tsaneva-Atanasova K., McArdle C.A. Gonadotropin-releasing hormone signaling: An information theoretic approach. Mol. Cell. Endocrinol. 2018; 463: 106-15. https://dx.doi.org/10.1016/j.mce.2017.07.028.
- Al-Sheyyab R.Y., Al-Taani B.M., Obeidat R.M., Alsmadi M.M., Masaedeh R.K., Sabat R.N. Delivery of peptidic gonadotropin releasing hormone antagonists. Curr. Drug Deliv. 2018; 15(5): 602-9. https://dx.doi.org/10.2174/1567201815666180214142300.
- De Sanctis V., Soliman A.T., Di Maio S., Soliman N., Elsedfy H. Long-term effects and significant Adverse Drug Reactions (ADRs) associated with the use of gonadotropin-releasing hormone analogs (GnRHa) for central precocious puberty: a brief review of literature. Acta Biomed. 2019; 90(3): 345-59.https://dx.doi.org/10.23750/abm.v90i3.8736.
- Lessey B.A. The role of the endometrium during embryo implantation. Hum. Reprod. 2000; 15(Suppl. 6): 39-50.
- Pirard C., Donnez J., Loumaye E. GnRH agonist as novel luteal support: results of a randomized, parallel group, feasibility study using intranasal administration of buserelin. Hum. Reprod. 2005; 20(7): 1798-804. https://dx.doi.org/10.1093/humrep/deh830.
- Галлямова Е.М., Перминова С.Г., Митюрина Е.В., Стрельченко Д.А. Влияние поддержки лютеиновой фазы цикла агонистом гонадотропин-рилизинг гормона на исходы программы ЭКО. Акушерство и гинекология. 2015; 7: 48-55. [Gallyamova E.M., Perminova S.G., Mityurina E.V., Strelchenko D.A. Impact of luteal-phase support with a GnRH agonist on the outcomes of IVF programs. Obstetrics and Gynecology. 2015; (7): 48-55. (in Russian)].
- Перминова С.Г., Митюрина Е.В., Савельева Е.М. Возможности использования агониста ГнРг для поддержания лютеиновой фазы в программе ЭКО. Акушерство и гинекология. 2018; 10: 72-9. [Perminova S.G., Mityurina E.V., Savelyeva E.M. Opportunities for using gonadotropin-releasing hormone agonist for luteal phase support in the in vitro fertilization program. Obstetrics and Gynecology. 2018; (10): 72-9. (in Russian)].https://dx.doi.org/10.18565/aig.2018.10.72-79.
- Della Corte L., Barra F., Mercorio A., Evangelisti G., Rapisarda A.M.C., Ferrero S., Bifulco G., Giampaolino P. Tolerability considerations for gonadotropin-releasing hormone analogues for endometriosis. Expert Opin. Drug Metab. Toxicol. 2020; 16(9): 759-68. https://dx.doi.org/10.1080/17425255.2020.1789591.
- Кошелева Н.М., Перминова С.Г., Власова Г.А., Кириллова А.О. Применение программы вспомогательных репродуктивных технологий у пациентки с системной красной волчанкой и антифосфолипидным синдромом. Акушерство и гинекология. 2020; 4: 224-9. [Kosheleva N.M., Perminova S.G., Vlasova G.A., Kirillova A.O. Application of assisted reproductive technology programs in a female patient with systemic lupus erythematosus and antiphospholipid syndrome. Obstetrics and Gynecology. 2020; (4): 224-9. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.4.224-229.
- Bourgain C., Devroey P. The endometrium in stimulated cycles for IVF. Hum. Reprod. Update. 2003; 9(6): 515-22. https://dx.doi.org/10.1093/humupd/dmg045.
Received 13.02.2023
Accepted 21.02.2023
About the Authors
Nikolai N. Rukhliada, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, St. Petersburg State Pediatric Medical University,Ministry of Health of Russia, +7(911)913-20-20, nickolasr@mail.ru, https://orcid.org/0000-0002-3548-0468, 194100, Russia, Saint Petersburg, Litovskaya str., 2.
Elena I. Birukova, Ph.D., Head of the Department of Gynecology No. 2, I.I. Dzhanelidze Saint Petersburg Research Institute of Emergence Care, +7(911)225-21-31, 79112252131@yandex.ru, 192242, Russia, Saint Petersburg, Budapeshtskaya str., 3А.