A systematic review of the efficacy and safety of dydrogesterone in the treatment of menstrual disorders in young patients, including early reproductive age

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective: To conduct a systematic review of recent publications on the mechanisms of action, clinical efficacy, and safety of dydrogesterone in patients of reproductive age, including early reproductive years.

Materials and methods: The literature search was conducted in the following databases: eLibrary, PubMed, ClinicalTrials.gov, ICTRP, Cochrane Library and Google Scholar for the period 2016-2025. A total of 927 publications were identified, resulting in the exclusion of duplicate articles (n = 95), articles that did not meet the inclusion criteria (n = 789), and those with insufficient data (n = 17). The selection was carried out according to certain criteria of relevance: clinical studies, study design, reported endpoints, dydrogesterone therapy, and patients of reproductive age and patients aged 18 years and younger, post-menarche.

Results: There was a full-text analysis of 43 articles, 12 of them met the inclusion criteria with a total number of observations of 2,817 patients. A summary of the data showed high efficacy of dydrogesterone in regulating the menstrual cycle, reducing the frequency of abnormal uterine bleeding, relieving the severity of dysmenorrhea and chronic pelvic pain in patients of the early reproductive period. The review describes pathogenetic mechanisms of action of dydrogesterone, including an immunomodulatory effect mediated by the suppression of the NF-kB/COX-2 pathway, synthesis of proinflammatory cytokines, and activation of anti-inflammatory mediators. These mechanisms help to restore endometrial receptivity, reduce the recurrence of abnormal uterine bleeding and the severity of pelvic pain.

Conclusion: This systematic review confirms the pathogenetic and clinical significance of dydrogesterone as an effective and safe therapeutic option for menstrual cycle disorders (irregular menstruation, abnormal uterine bleeding, dysmenorrhea) in patients of reproductive age, including early reproductive years. The use of dydrogesterone is characterized by good tolerability and high levels of patient satisfaction with the therapy.

Full Text

Restricted Access

About the authors

Elena P. Khashchenko

Academician Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology

Author for correspondence.
Email: khashchenko_elena@mail.ru
ORCID iD: 0000-0002-3195-307X

PhD, Senior Researcher at the 2nd Gynecological Department (Pediatric and Adolescent Gynecology)

Russian Federation, 4, Academic Oparin St., Moscow, 117997

Maria N. Alekseeva

Lomonosov Moscow State University

Email: alekseevamarydubai14@mail.ru
ORCID iD: 0000-0001-9795-0587

Student at the Faculty of Fundamental Medicine

Russian Federation, 1, Leninskie Gory, Moscow, 119991

Stanislav V. Pavlovich

Academician Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology; Sechenov First Moscow State Medical University

Email: s_pavlovich@oparina4.ru
ORCID iD: 0000-0002-1313-7079

PhD, Academic Secretary; Professor at the Department of Obstetrics, Gynecology, Perinatology and Reproductology of the Institute of Professional Education

Russian Federation, 4, Academic Oparin St., Moscow, 117997; Bldg. 2, 8, Trubetskaya St., Moscow, 119991

Elena V. Uvarova

Academician Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology; Sechenov First Moscow State Medical University

Email: elena-uvarova@yandex.ru
ORCID iD: 0000-0002-3105-5640

Corresponding Member of the RAS, Dr. Med. Sci., Professor, Head of the 2nd Gynecological Department (Pediatric and Adolescent Gynecology); Professor at the Department of Obstetrics, Gynecology, Perinatology and Reproductology of the Institute of Professional Education; President of the Association of Pediatric and Adolescent Gynecologists; Chief Freelance Specialist in Pediatric and Adolescent Gynecology at the Ministry of Health of the Russian Federation

Russian Federation, 4, Academic Oparin St., Moscow, 117997; Bldg. 2, 8, Trubetskaya St., Moscow, 119991

References

  1. Peña A.S., Witchel S.F., Hoeger K.M., Oberfield S.E., Vogiatzi M.G., Misso M. et al. Adolescent polycystic ovary syndrome according to the international evidence-based guideline. BMC Med. 2020; 18(1): 72. https://dx.doi.org/10.1186/s12916-020-01516-x
  2. Howe D., Duffy S., O’Shea M., Hawkey A., Wardle J., Gerontakos S. et al. Policies, guidelines, and practices supporting women’s menstruation, menstrual disorders and menopause at work: a critical global scoping review. Healthcare (Switzerland) 2023; 11(22): 2945. https://dx.doi.org/10.3390/healthcare11222945
  3. Mansour D., Hofmann A., Gemzell-Danielsson K. A review of clinical guidelines on the management of iron deficiency and iron-deficiency anemia in women with heavy menstrual bleeding. Adv. Ther. 2021; 38(1): 201-25. https://dx.doi.org/10.1007/s12325-020-01564-y
  4. Endometriosis. Guideline of European Society of Human Reproduction and Embryology – 2022. Reprod. Endocrinol. 2022; 66: 8-19. https://dx.doi.org/10.18370/2309-4117.2022.66.8-19
  5. Доброхотова Ю.Э., Сапрыкина Л.В., Филатова Л.А., Нариманова М.Р. Аномальные маточные кровотечения: алгоритмы ведения, методы терапии. РМЖ. Мать и дитя. 2020; 3(1): 55-60. [Dobrokhotova Yu.E., Saprykina L.V., Filatova L.A., Narimanova M.R. Abnormal uterine bleeding: management algorithms, treatment approaches. Russian Journal of Woman and Child Health. 2020; 3(1): 55-60 (in Russian)]. https://dx.doi.org/10.32364/ 2618-8430-2020-3-1-55-60
  6. Becker C.M., Bokor A., Heikinheimo O., Horne A., Jansen F., Kiesel L. et al. ESHRE guideline: Endometriosis. Hum. Reprod. Open. 2022; 2022(2): hoac009. https://dx.doi.org/10.1093/hropen/hoac009
  7. Gallagher J.S., DiVasta A.D., Vitonis A.F., Sarda V., Laufer M.R., Missmer S.A. The impact of endometriosis on quality of life in adolescents. J. Adolesc. Health. 2018; 63(6): 766-72. https://dx.doi.org/10.1016/j.jadohealth.2018.06.027
  8. Ott J., Egarter C., Aguilera A. Dydrogesterone after 60 years: a glance at the safety profile. Gynecol. Endocrinol. 2022; 38(4): 279-87. https://dx.doi.org/10.1080/09513590.2021.2016692
  9. Mirza F.G., Patki A., Pexman-Fieth C. Dydrogesterone use in early pregnancy. Gynecol. Endocrinol. 2016; 32(2): 97-106. https://dx.doi.org/10.3109/ 09513590.2015.1121982
  10. Griesinger G., Blockeel C., Tournaye H. Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard? Fertil. Steril. 2018; 109(5): 756-62. https://dx.doi.org/10.1016/j.fertnstert.2018.03.034
  11. Harlow S.D., Gass M., Hall J.E., Lobo R., Maki P., Rebar R.W. et al.; STRAW 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012; 19(4): 387-95. https://dx.doi.org/10.1097/gme.0b013e31824d8f40.
  12. Methley A.M., Campbell S., Chew-Graham C., McNally R., Cheraghi-Sohi S. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv. Res. 2014; 14: 579. https://dx.doi.org/10.1186/s12913-014-0579-0
  13. Liberati A., Altman D.G., Tetzlaff J., Mulrow C., Gøtzsche P.C., Ioannidis J.P.A. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. BMJ. 2009; 339: b2700. https://dx.doi.org/10.1136/ bmj.b2700
  14. Сальникова И.А., Уварова Е.В. Особенности применения дидрогестерона с целью регуляции менструального цикла после остановки маточного кровотечения в пубертатном периоде. Репродуктивное здоровье детей и подростков. 2012; 2: 42-51. [Salnikova I.A., Uvarova E.V. Features of the use of dydrogesterone to regulate the menstrual cycle after stopping uterine bleeding during puberty. Reproductive health of children and adolescents. 2012; 2: 42-51 (in Russian)].
  15. Андреева В.О. Оптимизация тактики ведения пациенток с рецидивами маточных кровотечений пубертатного периода. Эффективная фармакотерапия. Акушерство и гинекология. 2013; (4): 54-60. [Andreeva V.O. Optimization of the management tactics for patients with recurrent uterine bleeding during puberty. Effective pharmacotherapy. Obstetrics and gynecology. 2013; (4): 54-60 (in Russian)].
  16. Сальникова И.А., Уварова Е.В. Опыт применения дидрогестерона в целях остановки аномальных маточных кровотечений у девочек-подростков. Репродуктивное здоровье детей и подростков. 2014; 4(57): 54-63. [Sаlnikova I.A., Uvarova E.V. Experience of dydrogesterone application in order to arrest of abnormal uterine bleeding in adolescent girls. Reproductive health of children and adolescents. 2014; 4(57): 54-63 (in Russian)].
  17. Андреева В.О., Линде В.А., Аперян А.В. Дисменорея у подростков – диагностические трудности и лечебная тактика. Таврический медико-биологический вестник. 2016; 19(2): 10-4. [Andreeva V.O., Linde V.A., Aperyan A.V. Dysmenorrhea in adolescents – problems of diagnostics and treatment tactics. Tavricheskiy mediko-biologicheskiy vestnik. 2016; 19(2): 10-4 (in Russian)].
  18. Trivedi N., Chauhan N., Vaidya V. Effectiveness and safety of dydrogesterone in regularization of menstrual cycle: a post-marketing study. Gynecol. Endocrinol. 2016; 32(8): 667-71. https://dx.doi.org/10.3109/09513590.2016.1152238
  19. Wang L., Guan H.Y., Xia H.X., Chen X.Y., Zhang W. Dydrogesterone treatment for menstrual-cycle regularization in abnormal uterine bleeding – ovulation dysfunction patients. World J. Clin. Cases. 2020; 8(15): 3259-66. https://dx.doi.org/10.12998/WJCC.V8.I15.3259
  20. Сухих Г.Т., Адамян Л.В., Дубровина С.О., Баранов И.И., Беженарь В.Ф., Козаченко А.В., Радзинский В.Е., Оразов М.Р., Ярмолинская М.И., Олофссон Я.И. Пролонгированный циклический и непрерывный режимы применения дидрогестерона эффективны для уменьшения хронической тазовой боли у женщин с эндометриозом: результаты исследования «Орхидея». Акушерство и гинекология: новости, мнения, обучение. 2021; 9(4): 6-18. [Sukhikh G.N., Adamyan L.V., Dubrovina S.O., Baranov I.I., Bezhenar V.F., Kozachenko A.V., Radzinsky V.E., Orazov M.R., Yarmolinskaya M.I., Olofsson J.I. Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study. Obstetrics and Gynecology: News, Opinions, Training. 2021; 9(4): 6-18 (in Russian)]. https://dx.doi.org/10.1016/j.fertnstert.2021.07.1194
  21. Kitawaki J., Koga K., Kanzo T., Momoeda M. An assessment of the efficacy and safety of dydrogesterone in women with ovarian endometrioma: an open-label multicenter clinical study. Reprod. Med. Biol. 2021; 20(3): 345-351. https://dx.doi.org/10.1002/rmb2.12391
  22. Yasin A., Afzal M., Aziz U. A Comparison between the effectiveness of norethisterone and dydrogesterone for treatment of irregular menstrual cycle. Pakistan Journal of Medical and Health Sciences. 2021; 15(11): 2876-8. https://dx.doi.org/10.53350/pjmhs2115112876
  23. Иванишкина-Кудина О.Л. Аномальные маточные кровотечения раннего репродуктивного периода. Возможности терапии препаратом дидрогестерона Дюфастон. Репродуктивное здоровье. Восточная Европа. 2022; 12(2): 217-27. [Ivanishkina-Kudina O.L. Abnormal uterine bleeding in early reproductive age. Outlook of therapy with dydrogesterone Duphaston. Reproductive Health. Eastern Europe. 2022; 12(2): 217-27 (in Russian)]. https://dx.doi.org/10.34883/PI.2022.12.2.007
  24. Сальникова И.А., Уварова Е.В., Хащенко Е.П., Мамедова Ф.Ш. Особенности применения дидрогестерона для лечения маточного кровотечения в возрасте до 18 лет. Репродуктивное здоровье детей и подростков. 2022; 18(4): 49-65. [Salnikova I.A., Uvarova E.V., Khashchenko E.P., Mamedova F.Sh. Features of the use of dydrogesterone for the treatment of uterine bleeding in patients under the age of 18 years. Pediatric and adolescent reproductive health. 2022; 18(4): 49-65 (in Russian)]. https://dx.doi.org/10.33029/ 1816-2134-2022-18-4-49-65
  25. Уварова Е.В., Хащенко Е.П., Сальникова И.А., Андреева В.О., Фунда Н.А., Храмова Е.Е., Субботина С.В., Тулендинова А.И., Мардоян М.А., Городнова Е.А., Сухих Г.Т. Эффективность и безопасность применения дидрогестерона у подростков младше 18 лет с нарушениями менструального цикла. Данные ретроспективного исследования реальной клинической практики. Акушерство и гинекология. 2025; 1: 88-96. [Uvarova E.V., Khashchenko E.P., Salnikova I.A., Andreeva V.O., Funda N.A., Khramova E.E., Subbotina S.B., Tulendinova A.I., Mardoyan M.A., Gorodnova E.A., Sukhikh G.T. Retrospective real world data research program in adolescents under 18 years old with a history of dydrogesterone treatment for menstrual disorders. Obstetrics and Gynecology. 2025; (1): 88-96 (in Russian)]. https://dx.doi.org/10.18565/aig.2025.14
  26. Иванишкина-Кудина О.Л., Иконостасова И.В., Коротких О.В. Возможность применения дидрогестерона в комплексном лечении нарушений менструального цикла и клинического эндометриоза у женщин раннего и молодого репродуктивного возраста: обоснование и перспективы консервативной терапии. Репродуктивное здоровье Восточная Европа. 2021; 11(4): 487-95. [Ivanishkina-Kudina O.L., Iconostasova I.V., Korotkikh O.V. The possibility of using dydrogesterone in the complex treatment of menstrual irregularities and clinical endometriosis in women of early and young reproductive age: rationale and prospects for conservative therapy. Reproductive Health. Eastern Europe. 2021; 11(4): 487-95 (in Russian)]. https://dx.doi.org/10.34883/pi.2021.11.4.009
  27. Seeger H., Mueck A.O. Effects of dydrogesterone on the vascular system. Gynecol. Endocrinol. 2007; 23(S.1): 2-8. https://dx.doi.org/10.1080/09513590701584998
  28. Dansuk R., Unal O., Karsidag Y.K., Turan C. Evaluation of the effects of various gestagens on insulin sensitivity, using homeostatic model assessment, in postmenopausal women on hormone replacement therapy. Gynecol. Endocrinol. 2005; 20(1): 1-5. https://dx.doi.org/10.1080/09513590400020880
  29. Schweppe K.W. The place of dydrogesterone in the treatment of endometriosis and adenomyosis. Maturitas. 2009; 65(S.1): S23-7. https://dx.doi.org/10.1016/ j.maturitas.2009.11.011
  30. Tang W., Zhu X., Bian L., Zhang B. Research progress of dydrogesterone in the treatment of endometriosis. Eur. J. Obstet. Gynecol. Reprod. Biol. 2024; 296: 120-5. https://dx.doi.org/10.1016/j.ejogrb.2024.02.034
  31. Cottrell J.N., Witcher A.C., Comley K., Cunningham Jr M.W., Ibrahim T., Cornelius D.C. et al. Progesterone-induced blocking factor improves blood pressure, inflammation, and pup weight in response to reduced uterine perfusion pressure (RUPP). Am. J. Physiol. Regul. Integr. Comp. Physiol. 2021; 320(5): R719-27. https://dx.doi.org/10.1152/AJPREGU.00152.2020
  32. Schindler A.E. Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium. Maturitas. 2009; 65(S.1): S3-11. https://dx.doi.org/10.1016/j.maturitas.2009.10.011
  33. Yasuda K., Sumi G., Murata H., Kida N., Kido T., Okada H. The steroid hormone dydrogesterone inhibits myometrial contraction independently of the progesterone / progesterone receptor pathway. Life Sci. 2018; 207: 508-15. https://dx.doi.org/10.1016/j.lfs.2018.07.004
  34. Общая характеристика лекарственного препарата «Дидроменс» ЛП-№(010053)-(РГ-RU)-060525. Доступно по: https://pharma.eaeunion.org/pharma/registers/26/ru/register/registered-medicinal-products/ 668d12d030dcf88d7dd87118 [General characteristics of Didromens drug product LP-No. (010053)-(WG-RU)-060525. Available at: https://pharma.eaeunion.org/pharma/registers/26/ru/register/registered-medicinal-products/ 668d12d030dcf88d7dd87118 (in Russian)].
  35. Резюме клинических исследований, версия 1.0 от 19.06.2024 (информация может быть предоставлена по запросу на адрес info@binnopharmgroup.ru). [Summary of Clinical Studies, version 1.0 from 19.06.2024 (information can be provided upon request to info@binnopharmgroup.ru) (in Russian)].
  36. Peng C., Huang Y., Zhou Y. Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis. Arch. Gynecol. Obstet. 2021; 304(1): 231-52. https://dx.doi.org/10.1007/s00404-020-05900-z
  37. Mönckedieck V., Sannecke C., Husen B., Kumbartski M., Kimmig R., Tötsch M. et al. Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model. Mol. Hum. Reprod. 2009; 15(10): 633-43. https://dx.doi.org/10.1093/molehr/gap063
  38. Taniguchi F., Ota I., Iba Y., Toda T., Tagashira Y., Ohata Y. et al. The efficacy and safety of dydrogesterone for treatment of dysmenorrhea: an open-label multicenter clinical study. J. Obstet. Gynaecol. Res. 2019; 45(1): 168-75. https://dx.doi.org/10.1111/jog.13807

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Graphical model of searching for and analysing relevant publications of clinical studies on the use of dydrogesterone in reproductive age

Download (186KB)
Indexing metadata
3. Fig. 2. Effectiveness of dydrogesterone in patients with irregular menstruation: the proportion of patients who achieved regular menstrual cycles (%) and the frequency of recurrence after discontinuation are presented

Download (107KB)
Indexing metadata
4. Fig. 3. Percentage of patients in whom dydrogesterone was effective in stopping AMH and who subsequently maintained a regular menstrual cycle (%)

Download (95KB)
Indexing metadata
5. Fig. 4. Dynamics of pain severity in patients on the background of dydrogesterone application from the 5th to the 25th day of MC

Download (96KB)
Indexing metadata
6. Fig. 5. Schematically represented mechanism of realisation of anti-inflammatory and immunomodulatory effects of didrogesterone

Download (123KB)
Indexing metadata

Copyright (c) 2025 Bionika Media