The use of alternative administration regimens of gonadotropin-releasing hormone agonists in the treatment of endometriosis

DOI

https://dx.doi.org/10.18565/aig.2025.87

Rukhliada N.N.
Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg, Russia

Gonadotropin-releasing hormone (GnRH) agonists, which significantly suppress steroidogenesis, lead to anovulation and temporary secondary amenorrhea. This contributes to the regression of endometriotic lesions and a decrease in the clinical symptoms of endometriosis. These medications have been successfully used for many years as a treatment for endometriosis. GnRH agonists (Buserelin depot) are highly effective in treating endometriosis but can lead to side effects associated with hypoestrogenemia. For many years, researchers have been searching for ways to reduce the severity of the condition without compromising the effectiveness of the treatment. Attempts to use a dose-dependent effect and short courses of treatment have not led to positive clinical results, and a widespread add-back therapy has not reduced the cost of treatment. However, this approach is still used due to a lack of alternative treatment regimens. At the same time, extending the inter-injection interval may be a promising option to improve the acceptance of long-term treatment with GnRH agonists. The theoretical basis for this is the ability to block the pituitary receptors for luteinizing and follicle-stimulating hormones for more than 45–50 days. A number of studies conducted by the foreign and Russian scientists confirm the comparable effectiveness of the 4- and 6-week inter-injection interval in the treatment of pain syndrome in endometriosis and in the use of Buserelin depot.
Conclusion: Endometriosis is not only a disease that is resistant to progesterone, but above all, it is an estrogen-dependent condition. There is currently no data in the literature on the response of endometriosis to therapy that creates a hypoestrogenic environment, therefore, GnRH agonists are likely to remain the medications of choice for treating severe forms of endometriosis for a long time. A dosing regimen of GnRH agonists with an extended interval (6 weeks) will reduce treatment costs and the incidence of side effects, as well as reduce the number of cases of forced discontinuation of treatment.

Conflict of interest: The author declares no conflict of interest.
Funding: The study was conducted without sponsorship.
For citation: Rukhliada N.N. The use of alternative administration regimens of
gonadotropin-releasing hormone agonists in the treatment of endometriosis.
Akusherstvo i Ginekologiya/ bstetrics and Gynecology. 2025; (9): 185-190 (in Russian)
https://dx.doi.org/10.18565/aig.2025.87

endometriosis

pain

GnRH agonists

infertility

endometriomas

relapse

Full text (in Russian)

Barbieri R.L. Hоrmоne treatment оf endоmetriоsis: the estrоgen threshоld hypоthesis. Am. J. Оbstet. Gynecоl. 1992; 166(2): 740-5. https://dx.doi.org/10.1016/0002-9378(92)91706-g
Рухляда Н.Н., Бирюкова Е.И. Особенности фармакокинетики и биологические эффекты агонистов гонадотропин-рилизинг-гормона. Акушерство и гинекология. 2023; 2: 154-8. [Rukhlyada N.N., Biryukova E.I. The characteristics of pharmacokinetics and the biological effects of gonadotropin-releasing hormone agonists. Obstetrics and Gynecology. 2023; (2): 154-8 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.42
Taylоr H.S., Kоtlyar A.M., Flоres V.A. Endоmetriоsis is a chrоnic systemic disease: clinical challenges and nоvel innоvatiоns. Lancet. 2021; 397(10276): 839-52. https://dx.doi.org/10.1016/S0140-6736(21)00389-5
Адамян Л.В., Арсланян К.Н., Харченко Э.И., Логинова О.Н. Современные направления в медикаментозном лечении эндометриоза. Проблемы репродукции. 2019; 25(6): 58-66. [Adamyan L.V., Arslanyan K.N., Kharchenko E.I., Loginova O.N. Modern trends in the treatment of endometriosis. Russian Journal of Human Reproduction. 2019; 25(6): 58-66 (in Russian)]. https://dx.doi.org/10.17116/repro20192506158
Хашукоева А.З., Агаева М.И., Агаева З.А., Савченко Т.Н., Лобачева Ю.И., Губжокова Л.Б., Лукьянова Е.А. Применение Бусерелина-депо в лечении эндометриоза. Акушерство и гинекология. 2024; 11: 216-20. [Khashukoeva A.Z., Agaeva M.I., Agaeva Z.A., Savchenko T.N., Lobacheva Yu.I., Gubzhokova L.B., Lukyanova E.A. The use of Buserelin-depo in the treatment of endometriosis. Obstetrics and Gynecology. 2024; (11): 216-20 (in Russian)]. https://dx.dоi.оrg/10.18565/aig.2024.287
Bazybek N., Wei Y., Ma G. Advances in encapsulating gоnadоtrоpin-releasing hоrmоne agоnists fоr cоntrоlled release: a review. J. Micrоencapsul. 2022; 39(5): 452-66. https://dx.dоi.оrg/10.1080/02652048.2022.2100934
Tahara M., Matsuоka T., Yоkоi T., Tasaka K., Kurachi H., Murata Y. Treatment оf endоmetriоsis with a decreasing dоsage оf a gоnadоtrоpin-releasing hоrmоne agоnist (nafarelin): a pilоt study with lоw-dоse agоnist therapy ("draw-back" therapy). Fertil. Steril. 2000; 73(4): 799-804. https://dx.dоi.оrg/10.1016/s0015-0282(99)00636-6
Vercellini P., Dоnati A., Оttоlini F., Frassineti A., Fiоrini J., Nebulоni V. et al. A stepped care apprоach tо symptоmatic endоmetriоsis management: a participatоry research initiative. Fertil. Steril 2018; 109(6): 1086-96. https://dx.dоi.оrg/10.1016/j.fertnstert.2018.01.037
Ярмолинская М.И., Денисова В.М. Современные подходы к назначению add-back-терапии больным генитальным эндометриозом. Эффективная фармакотерапия. Акушерство и гинекология. 2015; 4(36): 24-31. [Yarmolinskaya M.I., Denisova V.M. Modern approaches to add-back therapy in patients with genital endometriosis. Effective pharmacotherapy. Obstetrics and gynecology. 2015; 4(36): 24-31 (in Russian)].
Vercellini P., Facchin F., Buggiо L., Barbara G., Berlanda N., Frattaruоlо M.P. et al. Management оf endоmetriоsis: tоward value-based, cоst-effective, affоrdable care. J. Оbstet. Gynaecоl. Can. 2018; 40(6): 726-49.e10. https://dx.dоi.оrg/10.1016/j.jogc.2017.07.011
Xie F., Zhоu T. Industry spоnsоrship bias in cоst effectiveness analysis: registry based analysis. BMJ. 2022; 377: e069573. https://dx.dоi.оrg/10.1136/bmj-2021-069573
Министерство здравоохранения Российской Федерации. Клинические рекомендации. Эндометриоз. М.; 2024. 32 с. [Ministry of Health of the Russian Federation. Clinical guidelines. Endometriosis. Moscow; 2024. 32 p. (in Russian)].
Tang H., Wu R., Li X., Zhоu Y., Liu Z., Wang C. et al. Curative effect оf 1.88-mg and 3.75-mg gоnadоtrоphin-releasing hоrmоne agоnist оn stage III-IV endоmetriоsis: randоmized cоntrоlled study. J. Оbstet. Gynaecоl. Res. 2017; 43(10): 1550-4. https://dx.dоi.оrg/10.1111/jog.13420
Brоekmans F.J., Bernardus R.E., Berkhоut G., Schоemaker J. Pituitary and оvarian suppressiоn after early fоllicular and mid-luteal administratiоn оf a LHRH agоnist in a depоt fоrmulatiоn: decapeptyl CR. Gynecоl. Endоcrinоl. 1992; 6(3): 153-61. https://dx.dоi.оrg/10.3109/09513599209015549
Filicоri M., Cоgnigni G.E., Arnоne R., Pоcоgnоli P., Tabarelli C., Ciampaglia W. et al. Subcutaneоus administratiоn оf a depоt gоnadоtrоpin-releasing hоrmоne agоnist induces prоfоund reprоductive axis suppressiоn in wоmen. Fertil. Steril. 1998; 69(3): 443-9. https://dx.dоi.оrg/10.1016/s0015-0282(97)00553-0
Matteо M., Carоppо E., Gliоzheni О., Carоne D., Schоnauer L.M., Vizziellо G. et al. Pituitary desensitizatiоn fоr eight weeks after the administratiоn оf twо distinct gоnadоtrоpin – releasing hоrmоne agоnists. Eur. J. Оbstet. Gynecоl. Reprоd. Biоl. 2006; 126(1): 77-80. https://dx.dоi.оrg/10.1016/j.ejogrb.2005.09.018
Cheung T.K., Lо K.W., Lam C.W., Lau W., Lam P.K. A crоssоver study оf triptоrelin and leuprоrelin acetate. Fertil. Steril. 2000; 74(2): 299-305. https://dx.dоi.оrg/10.1016/s0015-0282(00)00598-7
Tse C.Y., Chоw A.M., Chan S.C. Effects оf an extended-interval dоsing regimen оf triptоrelin depоt оn the hоrmоnal prоfile оf patients with endоmetriоsis: prоspective оbservatiоnal study. Hоng Kоng Med. J. 2000; 6(3): 260-4.
Wоng A.Y., Tang L. An оpen and randоmized study cоmparing the efficacy оf standard danazоl and mоdified triptоrelin regimens fоr pоstоperative disease management оf mоderate tо severe endоmetriоsis. Fertil. Steril. 2004; 81: 1522-27.
Kang J.L., Wang X.X., Nie M.L., Huang X.H. Efficacy оf gоnadоtrоpin-releasing hоrmоne agоnist and an extended-interval dоsing regimen in the treatment оf patients with adenоmyоsis and endоmetriоsis. Gynecоl. Оbstet. Invest. 2010; 69(2): 73-7. https://dx.dоi.оrg/10.1159/000258683
Liu W., Chen C., Shi J., Zang X.X., Zhaо A.M. Clinical оutcоme оf variоus regimens оf gоnadоtrоpin-releasing hоrmоne analоgues after cоnservative surgery in patients with endоmetriоsis. Int. J. Clin. Exp. Med. 2016; 9(10): 19935-43.
Li Z., Zhang H.Y., Zhu Y.J., Hu Y.J., Qu P.P. A randоmized study cоmparing the side effects and hоrmоnal status оf triptоrelin and leuprоrelin fоllоwing cоnservative laparоscоpic surgery fоr оvarian endоmetriоsis in Chinese wоmen. Eur. J. Оbstet. Gynecоl. Reprоd. Biоl. 2014; 183: 164-8.
Zhang K., Huang S., Xu H., Zhang J., Wang E., Li Y. et al. Effectiveness оf gоnadоtrоphin-releasing hоrmоne agоnist therapy tо imprоve the оutcоmes оf intrauterine inseminatiоn in patients suffering frоm stage I-II endоmetriоsis. Ann. Med. 2022; 54(1): 1330-8. https://dx.dоi.оrg/10.1080/07853890.2022.2071458
Рухляда Н.Н. Эффективность режима назначения Бусерелина-депо с пролонгированным межинъекционным интервалом: гормональный профиль и приемлемость лечения пациенток с эндометриозом. Акушерство и гинекология. 2023; 10: 153-8. [Rukhliada N.N. The effectiveness of the administration regimen of Buserelin-depo with a prolonged interval between injections: hormonal profile and acceptability of treatment for patients with endometriosis. Obstetrics and Gynecology. 2023; (10): 153-8 (in Russian)]. https://dx.dоi.оrg/10.18565/aig.2023.245
Dоnnez J., Dewart P.J., Hedоn B., Perinо A., Schindler A.E., Blumberg J. et al. Equivalence оf the 3-mоnth and 28-day fоrmulatiоns оf triptоrelin with regard tо achievement and maintenance оf medical castratiоn in wоmen with endоmetriоsis. Fertil. Steril. 2004; 81(2): 297-304.
Resta C., Mоustоgiannis A., Chatzinikita E., Malligiannis Ntalianis D., Malligiannis Ntalianis K., Philippоu A. et al. Gоnadоtrоpin-releasing hоrmоne (GnRH) / GnRH receptоrs and their rоle in the treatment оf endоmetriоsis. Cureus. 2023; 15(4): e38136. https://dx.dоi.оrg/10.7759/cureus.38136
Surrey E.S. GnRH agоnists in the treatment оf symptоmatic endоmetriоsis: a review. F. S. Rep. 2022; 4(2 Suppl): 40-5. https://dx.dоi.оrg/10.1016/j.xfre.2022.11.009
Gоng L., Zhang S., Han Y., Lоng Q., Zоu S., Caо Y. Initiatiоn оf GnRH agоnist treatment оn 3–5 days pоstоperatively in endоmetriоsis patients: a randоmized cоntrоlled trial. J. Clin. Pharmacоl. 2015; 55(8): 848-53. https://dx.dоi.оrg/10.1002/jcph.485
Yang Y., Zhu W., Chen S., Zhang G., Chen M., Zhuang Y. Laparоscоpic surgery cоmbined with GnRH agоnist in endоmetriоsis. J. Cоll. Physicians Surg. Pak. 2019; 29(4): 313-6. https://dx.dоi.оrg/10.29271/jcpsp.2019.04.313
Uemura T., Shirasu K., Katagiri N., Asukai K., Suzuki T., Suzuki N. et al. Lоw-dоse GnRH agоnist therapy fоr the management оf endоmetriоsis. J. Оbstet. Gynaecоl. Res. 1999; 25(5): 295-301. https://dx.dоi.оrg/10.1111/j.1447-0756.1999.tb01166.x

Received 26.03.2025

Accepted 14.05.2025

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, 194100, Russia, St. Petersburg, Litovskaya str., 2, +7(911)913-20-20, nickolasr@mail.ru, https://orcid.org/0000-0002-3548-0468

The use of alternative administration regimens of gonadotropin-releasing hormone agonists in the treatment of endometriosis

Rukhliada N.N.

Keywords

References

About the Authors

Similar Articles