Experience of treating patients with abnormal uterine bleeding associated with ovulatory dysfunction

Dikke G.B., Novichkov D.A., Zulkarneeva E.M., Amirova K.Z., Beraya A.E., Gartleb O.A., Cherezova Yu.M., Akhmetgaliev A.R.

1) F.I. Inozemtsev Academy of Medical Education, St. Petersburg, Russia; 2) Saratov State Medical University named after V.I. Razumovsky, Ministry of Health of Russia, Saratov, Russia; 3) Bashkir State Medical University, Ministry of Health of Russia, Ufa, Russia; 4) Central Regional Hospital, Timashevsk (Krasnodar Territory), Russia; 5) Stolitsa Clinic Network, Moscow, Russia; 6) Medical Center "Medgard", Saratov, Russia; 7) Regional Center for Reproductive Medicine "Dynasty", Samara, Russia; 8) Kazan State Medical University, Ministry of Health of Russia, Kazan, Russia

Abnormal uterine bleeding (AUB) associated with ovulatory disfunction (OD) is the most common finding among women with chronic AUB, accounting for 57.7% of cases. Oral progestogens are often prescribed for irregular and copious menstruation. However, a course of hormonal rehabilitation after AUB-OD may not be enough. Inositols have been shown to be highly effective in restoring ovulation, normalizing the menstrual cycle, correcting carbohydrate and lipid metabolism, and reducing body weight.
Objective: To evaluate the effectiveness of complex treatment consisting of a combination of gestagen, iron medication and complex containing myoinositol, D-chiroinositol (5:1), folic acid and manganese in reproductive-aged patients with abnormal uterine bleeding associated with type I–III ovulatory dysfunction.
Materials and methods: The multicentre study in real clinical practice included 2,042 women with OD. The patients received dydrogesterone or micronized progesterone for 3 cycles (from 14 to 25 days), a medication containing myoinositol 1000 mg, D-chiroinositol 200 mg, folic acid 200 mg, manganese 5 mg (Dikirogen) for 6 cycles, iron sulfate/ascorbic acid for 3–4 months (according to indications). The parameters of the menstrual cycle (MC), hemoglobin, serum ferritin, and body weight were assessed at 3, 6 and 12 months from the start of treatment.
Results: The age of the patients ranged from 18 to 45 years, the average age was 30 (25; 35) years. The number of patients with a normal MC rhythm after 3 and 6 months was observed in 76.5 and 90.9% of patients versus 46.9% before treatment, p<0.001, and with a moderate volume of menstruation in 77.9 and 89.9% versus 45.4%, respectively, p<0.001; iron deficiency anaemia decreased from 39.9% to 18.2% of patients after 3 months, p<0.001, and there were no patients with anaemia by 6 months. Menstrual cyclicity remained at the achieved level, and the volume of blood loss decreased statistically significantly by 12 months. BMI decreased from 26.8 (21.3; 27.3) to 23.4 (21.3; 24.3) kg/m2 by 6 months of treatment, p=0.001, and stabilized at this level until 12 months.
Conclusion: Therapy for OD with progestin/Dikirogen in the first 3 months followed by administration of only Dikirogen for 3 months and symptomatic treatment with iron is effective in achieving regular menstrual cycle and volume of menstrual blood loss, eliminating anaemia and normalizing body weight.

Authors’ contributions: Dikke G.B. – analysis of the results after statistical processing of clinical material and their interpretation, search for literary sources, writing an article and editing it after reviewing; Novichkov D.A., Zulkarneeva E.M. – development of the concept, design and program of the study, supervision during the study; Amirova K.Z., Beraya A.E., Gartleb O.A., Cherezova Yu.M. – organization of research at clinical bases, supervision during the study; Akhmetgaliev A.R. – statistical processing of research results.
Conflicts of interest: The authors report no conflicts of interest and guarantee that the article is the original work of the authors.
Funding: Publication of the article was supported by Invar LLC. Company employees did not take part in writing the text of the article or editing it.
Acknowledgements: The authors express their gratitude to Svetlana A. Bergal, Svetlana A. Grigorieva, Lolakhon U. Isakova (Samara), Farida A. Burnasheva, Gulnara A. Voedilova, Ekaterina V. Kosolapova, Natalia N. Firsova, 
Gulnaz K. Shaykhutdinova, Gulnara I. El Ayubi (Kazan), Irina V. Voetskaya (Ulyanovsk), Valeria A. Kovaleva (Stavropol), Olga V. Ivanova (Chelyabinsk), Elena A. Maximova, Tatiana N. Skidan (Moscow), Anastasia A. Matveeva, Tatiana S. Noritsina (Yekaterinburg), Victoria V. Molchanova, Galina V. Morozova (Krasnodar), Lilia I. Samoylenko (Pervouralsk), Marina A. Skvortsova (Saratov) for the participation in collecting clinical material.
Ethical Approval: The research protocol met the requirements of the Helsinki Declaration of the World Medical Association (revision of the 64th General Assembly of the World Medical Association, Fortaleza, Brazil, 2013), regulations of the International Ethical Guidelines for Biomedical Research Involving Human Subjects (ed. 2002), the National Standard of the Russian Federation R52379-2005 “Good Clinical Practice” (2005), other legislative and regulatory documents of the Russian Federation. The permission of the local Ethics Committee was not required (the funds were used in accordance with the instructions of the manufacturers).
Patient Consent for Publication: The patients provided an informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Dikke G.B., Novichkov D.A., Zulkarneeva E.M., Amirova K.Z., Beraya A.E., Gartleb O.A., Cherezova Yu.M., Akhmetgaliev A.R. Experience of treating patients with abnormal uterine bleeding associated with ovulatory dysfunction. 
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (3): 142-152 (in Russian)


abnormal uterine bleeding
ovarian dysfunction
folic acid
iron deficiency anaemia


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Received 09.02.2024

Accepted 18.03.2024

About the Authors

Galina B. Dikke, Dr. Med. Sci., Professor, Department of Obstetrics and Gynecology with a Course of Reproductive Medicine, F.I. Inozemtsev Academy of Medical Education, 190013, Russia, Saint Petersburg, Moskovskiy Ave., 22 Liter M, galadikke@yandex.ru, https://orcid.org/0000-0001-9524-8962
Denis A. Novichkov, PhD, Associate Professor of the Department of Obstetrics and Gynecology of the Pediatric Faculty, Saratov State Medical University named after
V.I. Razumovsky, Ministry of Health of Russia; Chief freelance specialist in obstetrics and gynecology of the Ministry of Health of the Saratov region, dnovichkov@mail.ru, https://orcid.org/0000-0001-6945-835Х
Elmira M. Zulkarneeva, PhD, Associate professor, Associate professor of the Department of Obstetrics and Gynecology No. 1, Bashkir State Medical University,
Ministry of Health of Russia, 450008, Republic of Bashkortostan, Ufa, Lenin str., 3, zulkarneeva.elmira@yandex.ru, https://orcid.org/0000-0003-0724-8765
Karina Z. Amirova, obstetrician-gynecologist of the highest category, head of the residential complex of the Central Regional Hospital, Timashevsk (Krasnodar Territory), karinaamirowa@yandex.ru
Astanda E. Beraya, obstetrician-gynecologist, doctor of the highest category, Head Physician of the Stolitsa Clinic Network,
119002, Russia, Moscow, B. Vlasevsky lane, 9, doctor_beraia@mail.ru
Oksana A. Gartleb, obstetrician-gynecologist, Head of the Department of Gynecology, MC “Medgard”, 410028, Russia, Saratov, Radishchev str., 2, gar_nast@mail.ru
Yulia M. Cherezova, PhD, obstetrician-gynecologist, reproductologist, Regional Center for Reproductive Medicine “Dynasty”, Russia, Samara, Frunze str., 43,
cherezova-j@mail.ru, https://orcid.org/0009-0001-8333-5089
Artur R. Akhmetgaliev, PhD, Assistant at the Department of Obstetrics and Gynecology named after Prof. V.S. Gruzdev, Kazan State Medical University,
Ministry of Health of Russia, ahmetgaliev.artur@yandex.ru, https://orcid.org/0000-0003-2786-3415, Scopus Author ID: 57191958800
Corresponding author: Galina B. Dikke, galadikke@yandex.ru

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