Efficacy and safety of mifepristone in patients with uterine fibroids
Tikhomirov A.L., Orazov M.R., Melkozerova O.A., Smetnik A.A., Ermakova E.I., Katkova N.Yu., Bezhenar V.F., Antropova E.Yu., Rymashevsky A.N., Mikhelson A.A., Baranova E.S., Grigorian A.E.
Objective: To evaluate the efficacy and safety of Gynestril, 50 mg tablet, in patients with symptomatic uterine fibroids in routine clinical practice.
Materials and methods: This was an open, multicenter, non-interventional, prospective study conducted on the basis of seven Russian clinical centers between 2022 and 2023 in order to investigate the therapeutic efficacy and safety of Gynestril in patients with symptomatic uterine fibroids in routine clinical practice (GYNNEO). All patients (n=234) were administered the drug orally, in the form of a single tablet, once a day on days 1-3 of the menstrual cycle for a period of three months (one course of treatment). The efficacy and safety of the treatment were evaluated during the patients’ visits to the centers: before the drug was prescribed, immediately after completing the treatment with its course for three months and three months after completing the treatment. Efficacy was assessed by changes in the volume and largest linear size of the dominant myomatous node and nodes 2 and 3, which were considered to be the second and third nodes in diameter after the dominant node (provided that their initial diameter was less than 1.5 cm), uterine volume, number of visualized nodes, endometrial thickness, resistance index (RI) and blood flow velocity in the nodes, hemoglobin level, dynamics of symptom severity according to the 5-point Likert scale, etc. The incidence and characteristics of adverse and serious events were considered in the safety assessment.
Results: According to the ultrasound data, the volume of the dominant myomatous node decreased by 33% after three months of therapy with Gynestril and by 59.5% after three months of follow-up compared to baseline (pre-treatment) level. A number of other efficacy endpoints also showed positive trends during the study. They included decreases in volume of nodes 2 and 3, uterine volume, maximum linear size of the nodes, increased RI, and decreased blood flow velocity in the nodes. The severity of the symptoms associated with the disease (pain, dyspareunia, and symptoms of compression) was found to decrease with the complete elimination of moderate and severe symptoms after three months of therapy. Half of the patients had amenorrhea after the treatment and it persisted in 101/234 (43%) patients for three months after completing the treatment with Gynestril. During the study, there were 26/226 (11%) adverse events related to treatment.
Conclusion: The study demonstrates that treatment with Gynestril results in a statistically significant decrease in the volume of myomatous nodes after three months of therapy (immediately after the course) and this effect persists for three months following the completion of the course of therapy. Therapy with Gynestril controls and reduces the severity of symptoms of the disease and the amount of menstrual blood loss. The drug is generally well tolerated by patients.
Authors’ contributions: Tikhomirov A.L. – developing the concept and design of the study, writing the text; Tikhomirov A.L., Orazov M.R., Melkozerova O.A., Smetnik A.A., Ermakova E.I., Katkova N.Yu., Bezhenar V.F., Antropova E.Yu., Rymashevsky A.N., Mikhelson A.A., Baranova E.S., Grigorian A.E. – collecting and processing of the material; Baranova E.S., Grigorian A.E. – statistical processing of the data; Tikhomirov A.L., Ermakova E.I., Katkova N.Yu., Bezhenar V.F. – editing the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article was prepared with the support of Nizhpharm JSC. The opinion of the authors may not coincide with the opinion of the company.
Patient Consent for Publication: The patients signed 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: Tikhomirov A.L., Orazov M.R., Melkozerova O.A., Smetnik A.A., Ermakova E.I., Katkova N.Yu.,
Bezhenar V.F., Antropova E.Yu., Rymashevsky A.N., Mikhelson A.A., Baranova E.S., Grigorian A.E.
Efficacy and safety of mifepristone in patients with uterine fibroids.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (12): 166-175 (in Russian)
https://dx.doi.org/10.18565/aig.2024.317
Keywords
mifepristone
uterine fibroid
myomatous nodes
non-interventional study
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Received 10.12.2024
Accepted 18.12.2024
About the Authors
Alexander L. Tikhomirov, Professor, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology of the Medical Faculty, Russian University of Medicine,Ministry of Health of Russia, 127473, Russia, Moscow, Delegatskaya str., 20/1, +7(926)066-10-26, tikhomiroval@yandex.ru
Mekan R. Orazov, Professor, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology with a course in perinatology of the Medical Institute, RUDN University, 117198, Russia, Moscow, Miklukho-Maklaya str., 6, +7(915)237-52-92, omekan@mail.ru, https://orcid.org/0000-0002-5342-8129
Oxana A. Melkozerova, Dr. Med. Sci., Associate Professor, Deputy Director for Science, Urals Research Institute of Maternity and Child Care, Ministry of Health of Russia, 620028, Russia, Yekaterinburg, Repin str., 1, +7(922)219-45-06, abolmed1@mail.ru, https://orcid.org/0000-0002-4090-0578
Antonina A. Smetnik, PhD, Head of the Department of Gynecological Endocrinology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4; President of the Russian Society of Specialists in Gynecological Endocrinology and Menopause, +7(495)531-44-44, a_smetnik@oparina4.ru, https://orcid.org/0000-0002-0627-3902
Elena I. Ermakova, PhD, Senior Researcher at the Department of Gynecological Endocrinology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4; Vice-President of the Russian Society of Specialists in Gynecological Endocrinology and Menopause, +7(916)848-37-46, e_ermakova@oparina4.ru, https://orcid.org/0000-0002-6629-051X
Nadezhda Yu. Katkova, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Additional Vocational Education, Privolzhsky Research Medical University, Ministry of Health of Russia, 603005, Russia, Nizhny Novgorod, Minin and Pozharsky sqr., 10/1, +7(910)381-38-51, katkova_nu@inbox.ru
Vitaly F. Bezhenar, Dr. Med. Sci., Professor, Head of the Department of Obstetrics, Gynecology and Neonatology/Reproductology, Head of the Clinic of Obstetrics and Gynecology, Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia, 197022, Russia, St. Petersburg, Leo Tolstoy str., 6-8, +7(812)338-78-66,
bez-vitaly@yandex.ru, https://orcid.org/0000-0002-7807-4929
Elena Yu. Antropova, PhD, Associate Professor at the Department of Obstetrics and Gynecology, Kazan State Medical Academy, 420012, Russia, Republic of Tatarstan, Kazan, Mushtari str., 11; obstetrician-gynecologist, Clinic «Institute of Health and Longevity», +7(843)267-61-52, antropoval@mail.ru, https://orcid.org/0000-0002-5991-5163
Alexandr N. Rymashevsky, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology No. 1, Rostov State Medical University, Ministry of Health of Russia, 344022, Russia, Rostov-on-Don, Nakhichevan Lane, 29, +7(918)554-78-98, rymashevskyan@mail.ru, https://orcid.org/0000-0003-3349-6914
Anna A. Mikhelson, Dr. Med. Sci., Associate Professor, Head of the Department of Reproductive Functions Preservation, Urals Research Institute of Maternity and Child Care, Ministry of Health of Russia, 620028, Russia, Yekaterinburg, Repin str., 1, +7(900)198-67-26, ann_lukach@list.ru, https://orcid.org/0000-0003-1709-6187
Ekaterina S. Baranova, Teaching Assistant, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Additional Vocational Education, Privolzhsky Research Medical University, Ministry of Health of Russia, 603005, Russia, Nizhny Novgorod, Minin and Pozharsky sqr., 10/1, +7(910)396-54-51, ekaterinabaranova94@mail.ru
Anna E. Grigorian, PhD Student at the Department of Obstetrics, Gynecology and Neonatology, Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia, 197022, Russia, St. Petersburg, Leo Tolstoy str., 6-8, +7(812)338-67-15, annagrigoryan2112@mail.ru, https://orcid.org/0000-0002-1674-7753
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