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Physiological Aspects of the Application of Gonadotropin-Releasing Hormone Agonists in Clinical and Experimental Obstetrics and Gynecology

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Abstract

A literature search was carried out to analyze the works on the application of gonadotropin-releasing hormone (GnRH) agonists in clinical obstetrics and gynecology, as well as in experimental studies. Here we address the physiological aspects of the GnRH influence on the ovaries and uterus both in normal and some pathological conditions. It is concluded that long-term use of GnRH agonists suppresses ovulation and induces a menopause-like condition. GnRH agonist infusion is a simple method of suppressing the production of luteinizing and follicle-stimulating hormones, as well as folliculogenesis. In the ovaries, granulosa cell activity is inhibited by the suppression of DNA synthesis and induction of apoptosis with simultaneous stimulation of cell differentiation in preovulatory follicles. This condition is reversible, with fertility being preserved. Due to rapid uterine involution after the use of GnRH analogs, it is possible to delay or even arrest uterine myoma progression followed by the disappearance of its symptoms. With uterine hypotrophy, the endometrium corresponds to an atrophic or resting proliferative type. At the same time, there is quite opposite evidence that long-term use of GnRH promotes endometrial hyperplasia and endometritis. GnRH-based drugs are successfully used to treat benign and malignant processes in the ovaries and uterus, as well as to affect metastases, although there are studies showing that the direct effect of GnRH on tumors is poorly pronounced. There are apprehensions that gonadotropins can even stimulate the development of ovarian cancer by acting on certain receptors. Most authors report a good protective capacity of GnRH agonists during chemotherapy, but there is evidence of little or no protective effect of this group of drugs. Either way, the inconsistency of publications on each of the aspects of GnRH effects emphasizes the advisability to further not only applied but also fundamental studies in this field.

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Funding

This work was supported by the Fundamental Scientific Research Programs for 2022–2024 “The study of morphological and molecular features of organopathies at isolated and combined effects of leading metabolic risk factors of chronic non-communicable diseases” (subject code FGMU-2022-0030, state registration no. 122032300164-6) and by Russian State Budget Funded Project of ICBFM SB RAS 1.6.12. “Fundamentals of health saving”. The work was performed using the equipment of the Proteomic Analysis Center for Collective Use, supported by the funding from the Russian Ministry of Education and Science (agreement no. 075-15-2021-691). The authors did not receive financial support from manufacturers of equipment, reagents and drugs.

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  1. Institute of Molecular Pathology and Pathomorphology, Federal Research Center for Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Novosibirsk, Russia

    I. V. Maiborodin, A. K. Pichigina, V. I. Maiborodina & E. L. Lushnikova

  2. Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russia

    I. V. Maiborodin

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  1. I. V. Maiborodin
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Conceptualization and experimental design (I.V.M., E.L.L.); data collection and processing (I.V.M., V.I.M., E.L.L.); writing the manuscript (I.V.M., A.K.P., E.L.L.); editing (I.V.M., A.K.P., V.I.M., E.L.L.).

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 11, pp. 1393–1409https://doi.org/10.31857/S0869813922110061.

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Maiborodin, I.V., Pichigina, A.K., Maiborodina, V.I. et al. Physiological Aspects of the Application of Gonadotropin-Releasing Hormone Agonists in Clinical and Experimental Obstetrics and Gynecology. J Evol Biochem Phys 58, 1865–1878 (2022). https://doi.org/10.1134/S0022093022060163

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