The effect of indolcarbinol on cyclic mastalgia in benign mammary dysplasia in routine clinical practice ("APHRODITE" study)
- Authors: Ashrafyan L.A.1, Rozhkova N.I.2,3, Prokopenko S.P.2,3, Meskikh E.V.4,5, Artymuk N.V.6, Belotserkovtseva L.D.7,8, Dolgushina V.F.9, Korotkikh N.V.10,11, Kuznetsova L.V.12, Kukarskaya I.I.13,14, Kononenko T.S.15, Marochko T.Y.6, Sokolov K.A.16, Verbitskaya Y.S.16
-
Affiliations:
- Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
- P. Hertsen Moscow Oncology Research Institute, National Medical Research Radiological Center, Ministry of Health of Russia
- Peoples’ Friendship University of Russia
- Pirogov Russian National Research Medical University, Ministry of Health of Russia
- Russian Scientific Center of Roentgenoradiology, Ministry of Health of Russia
- Kemerovo State Medical University, Ministry of Health of Russia
- Surgut District Clinical Center for Maternal and Child Health
- Surgut State University
- South Ural State Medical University, Ministry of Health of Russia
- N.N. Burdenko Voronezh State Medical University, Ministry of Health of Russia
- Voronezh Regional Clinical Oncological Dispensary
- Almazov National Medical Research Center, Ministry of Health of Russia
- Tyumen State Medical University, Ministry of Health of Russia
- Tyumen Regional Perinatal Center
- Kuban State Medical University, Ministry of Health of Russia
- Alcea LLC
- Issue: No 2 (2024)
- Pages: 134-142
- Section: Exchange of Experience
- URL: https://journals.eco-vector.com/0300-9092/article/view/631365
- DOI: https://doi.org/10.18565/aig.2024.35
- ID: 631365
Cite item
Open Access
Access granted
Abstract
Objective: The primary aim of the study was to evaluate the effect of Indinol Forto on pain syndrome in various benign breast diseases. The secondary aims included the assessment of the effect on the number and size of cysts in the mammary glands and evaluation of additional data on safety in routine clinical practice.
Materials and methods: These are the results of a prospective observational study “APHRODITE” of the drug Indinol Forto (indolcarbinol) which was conducted in 9 research centers of the Russian Federation with the participation of 100 women over the age of 18.
Results: Indolcarbinol therapy had a positive effect on reducing pain syndrome (mastodynia) after 3–6 months of treatment. The results of the ultrasound assessment and mammography showed a decrease in the total size of cysts, as well as a decrease in the proportion of women with dilated ducts of the mammary glands after 3 months of treatment. Longer use of indolcarbinol (6 months) was associated with a stronger effect. The patients tolerated indolcarbinol well and did not have undesirable or side effects.
Conclusion: The results of the study showed that indolcarbinol (Indinol Forto) caused a decrease in pain syndrome in patients with mastodynia in benign mammary dysplasia after 3–6 months of treatment. Indolcarbinol also resulted in a decrease in the total size of cysts and decrease in dilated ducts of the mammary glands in some women after 3 months of treatment. Thus, indolcarbinol appeared to be the only non-hormonal drug at the moment with a proven effect on the structure of breast tissue according to the results of the BI-RADS assessment.
Full Text
About the authors
Lev A. Ashrafyan
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Author for correspondence.
Email: levaa2004@yahoo.com
Academician of the Russian Academy of Sciences, Professor, Dr.Med. Sci., Head of the Institute of Oncogynecology and Mammology
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Nadezhda I. Rozhkova
P. Hertsen Moscow Oncology Research Institute, National Medical Research Radiological Center, Ministry of Health of Russia; Peoples’ Friendship University of Russia
Email: nrozhkova2013@yandex.ru
ORCID iD: 0000-0003-0920-1549
SPIN-code: 8478-1840
Honored Scientist of the Russian Federation, Professor, Dr.Med. Sci., Head of the National Center for Oncology of the Reproductive Organs, Professor of the Department of Clinical Mammology, Radiation Diagnostics and Radiation Therapy of the FNMO MI
Russian Federation, 125284, Moscow, 2nd Botkinsky proezd, 3; 117198, Moscow, Miklukho-Maklaya str., 6Sergey P. Prokopenko
P. Hertsen Moscow Oncology Research Institute, National Medical Research Radiological Center, Ministry of Health of Russia; Peoples’ Friendship University of Russia
Email: prokopenkosp@gmail.com
ORCID iD: 0000-0002-0369-5755
SPIN-code: 6987-9294
Scopus Author ID: 7004120546
MD, PhD, Associate Professor, Head of the Department of Complex Diagnostics and Interventional Radiology in Mammology, Head of the Department of Clinical Mammology, Radiation Diagnostics and Radiation Therapy of the FNMO MI
Russian Federation, 125284, Moscow, 2nd Botkinsky proezd, 3; 117198, Moscow, Miklukho-Maklaya str., 6Elena V. Meskikh
Pirogov Russian National Research Medical University, Ministry of Health of Russia; Russian Scientific Center of Roentgenoradiology, Ministry of Health of Russia
Email: meskihelena@rambler.ru
Dr.Med. Sci., Professor of the Department of X-ray Radiology, doctor of the highest category, Chief Researcher at X-ray Radiological Laboratory
Russian Federation, 117997, Moscow, st. Profsoyuznaya, 86; 117997 Moscow, Profsoyuznaya str., 86Natalia V. Artymuk
Kemerovo State Medical University, Ministry of Health of Russia
Email: artymuk@gmail.com
ORCID iD: 0000-0001-7014-6492
Dr.Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology named after Professor G.A. Ushakova
Russian Federation, 650060, Kemerovo, Voroshilova str., 22aLarisa D. Belotserkovtseva
Surgut District Clinical Center for Maternal and Child Health; Surgut State University
Email: Lbelotserkovtseva@gmail.com
Dr.Med. Sci., Professor, Honored Doctor of the Russian Federation, President of the Surgut District Clinical Center for Maternal and Child Health, Head of Department of Obstetrics and Gynecology
Russian Federation, 628403, Khanty-Mansiysk Autonomous Okrug – Ugra, Surgut, Lenin Ave., 1; SurgutValentina F. Dolgushina
South Ural State Medical University, Ministry of Health of Russia
Email: dolgushinavf@yandex.ru
Professor, Dr.Med. Sci., Head of the Department of Obstetrics and Gynecology
Russian Federation, 454092, Chelyabinsk, Vorovskogo str., 64Natalia V. Korotkikh
N.N. Burdenko Voronezh State Medical University, Ministry of Health of Russia; Voronezh Regional Clinical Oncological Dispensary
Email: kornat78@mail.ru
MD, PhD, Associate Professor of Oncology Department, Head of the Department, Voronezh Regional Clinical Oncology Dispensary
Russian Federation, 394036, Voronezh, Studencheskaya str., 10; 394036, Voronezh, Vaitsekhovskogo str., 4Lyubov V. Kuznetsova
Almazov National Medical Research Center, Ministry of Health of Russia
Email: Krivo73@mail.ru
MD, PhD, Associate Professor of the Department of Obstetrics and Gynecology with the clinic of the institute of medical education, Head of the Research laboratory of Reproduction and Women’s Health
Russian Federation, 197341, St. Petersburg, Akkuratova str., 2Irina I. Kukarskaya
Tyumen State Medical University, Ministry of Health of Russia; Tyumen Regional Perinatal Center
Email: kukarskaya@mail.ru
Dr.Med. Sci., Professor of the Department of Obstetrics, Gynecology and Reanimatology with a Course of Clinical Laboratory Diagnostics, Tyumen State Medical University, Chief Physician, Chief specialist in obstetrics and gynecology, Department of Health of the Tyumen Region, Honored doctor of the Russian Federation, Honorary healthcare worker of the Tyumen region
Russian Federation, 625023, Tyumen, Odesskaya str., 54; TyumenTatyana S. Kononenko
Kuban State Medical University, Ministry of Health of Russia
Email: kononenkotc@yandex.ru
MD, PhD, Assistant of the Department of Obstetrics, Gynecology and Perinatology, Faculty of Education and Training
Russian Federation, 350063, Krasnodar, Mitrofan Sedin str., 4 (Central microdistrict)Tatiana Yu. Marochko
Kemerovo State Medical University, Ministry of Health of Russia
Email: marochko.2006.68@mail.ru
ORCID iD: 0000-0001-5641-5246
MD, PhD, Associate Professor of the Department of Obstetrics and Gynecology named after Professor G.A. Ushakova
Russian Federation, 650060, Kemerovo, Voroshilova str., 22a
Kirill A. Sokolov
Alcea LLC
Email: kirill.sokolov@alceapharma.ru
ORCID iD: 0000-0002-8358-3963
MD, obstetrician-gynecologist, Medical Director
Russian Federation, 129110, Moscow, Olimpiysky Ave., 16, bld. 5Yulia S. Verbitskaya
Alcea LLC
Email: Yulia.verbitskaya@alceapharma.ru
ORCID iD: 0009-0004-2960-8455
MD, PhD, Medical Advisor
Russian Federation, 129110, Moscow, Olimpiysky Ave., 16, bld. 5References
- Рожкова Н.И., Андреева Е.Н., Каприн А.Д. Мастопатии. М.: ГЭОТАР-Медиа; 2019. [Rozhkova N.I., Andreeva E.N., Kaprin A.D. Mastopathy. Moscow: GEOTAR-Media; 2019. (in Russian)].
- Керчелаева С.Б., Сметник А.А., Беспалов В.Г. Мастопатия и профилактика рака молочной железы как междисциплинарная проблема. РМЖ. 2016; 15: 1018-25. [Kerchelaeva S.B., Smetnik A.A., Bespalov V.G. Mastopathy and breast cancer prevention as interdisciplinary problem. RMJ. 2016; (15): 1018-25. (in Russian)].
- Кулагина Н.В. Терапия фиброзно-кистозной болезни молочных желез у пациенток с миомой матки. Опухоли женской репродуктивной системы. 2010; 1: 40-3. [Kulagina NV. Therapy for fibrocystic breast disease in patients with uterine myoma. Tumors of Female Reproductive System. 2010; (1): 40-3. (in Russian)]. https://dx.doi.org/10.17650/1994-4098-2010-0-1-40-43.
- Инструкция по медицинскому применению лекарственного препарата "Индинол Форто". РУ № ЛП 002010-260422. [Instructions for the medical use of the drug "Indinol Forto". RU # LP 002010-260422. (in Russian)].
- Киселев В.И., Сметник В.П., Сутурина Л.В., Селиванов С.П., Рудакова Е.Б., Рахматуллина И.Р., Андреева Е.Н., Фадеева Н.И., Хасанов Р.Ш., Кулагина Н.В., Рожкова Н.И., Артымук Н.В., Гависова А.А., Муйжнек Е.Л., Кузнецов И.Н., Друх В.М. Индолкарбинол (Индинол Форто) – метод мультитаргетной терапии при циклической мастодинии. Акушерство и гинекология. 2013; 7: 56-62. [Kiselev V.I., Smetnik V.P., Suturina L.V., Selivanov S.P., Rudakova E.B., Rakhmatullina I.R., Andreyeva E.N., Fadeyeva N.I., Khasanov R.Sh., Kulagina N.V., Rozhkova N.I., Artymuk N.V., Gavisova A.A., Muizhnek E.L., Kuznetsov I.N., Drukh V.M. Indole carbinol (Indinol Forto) is a multitargeted therapy option for cyclic mastodynia. Obstetrics and Gynecology. 2013; (7): 56-62. (in Russian)].
- Тазина Т.В. Патогенетически обоснованная терапия циклической масталгии. Акушерство и гинекология. 2020; 9: 187-90. [Tazina T.V. Pathogenetically based therapy for cyclic mastalgia. Obstetrics and Gynecology. 2020; (9): 187-90. (in Russian)]. https://dx.doi.org/10.18565/ aig.2020.9.187-190.
- Кравченко Е.Н., Набока М.В. Лечение диффузных доброкачественных заболеваний молочной железы. Акушерство и гинекология. 2023; 2: 140-5. [Kravchenko E.N., Naboka M.V. Treatment for diffuse benign breast diseases. Obstetrics and Gynecology. 2023; (2): 140-5. (in Russian)]. https://dx.doi.org/10.18565/aig.2023.25.
- Министерство здравоохранения Российской Федерации. Клинические рекомендации "Доброкачественная дисплазия молочной железы". 2020. [Ministry of Health of the Russian Federation. Clinical guidelines "Benign Breast Dysplasia." 2020. (in Russian)].
- Rahman K.W., Aranha O.P., Sarkar F.H. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells. Nutr. Cancer. 2003; 45(1): 101-12. https://dx.doi.org/10.1207/S15327914NC4501_12.
- Marconett C.N., Sundar S.N., Tseng M., Tin A.S., Tran K.Q., Mahuron K.M. et al. Indole-3-carbinol downregulation of telomerase gene expression requires the inhibition of estrogen receptor-alpha and Sp1 transcription factor interactions within the hTERT promoter and mediates the G1 cell cycle arrest of human breast cancer cells. Carcinogenesis. 2011; 32(9): 1315-23. https://dx.doi.org/ 10.1093/carcin/bgr116.
- Michnovicz J.J., Bradlow H.L. Induction of estradiol metabolism by dietary indole-3-carbinol in humans. J. Natl. Cancer Inst. 1990; 82(11): 947-9. https://dx.doi.org/10.1093/jnci/82.11.947.
- Hasan H., Ismail H., El-Orfali Y., Khawaja G. Therapeutic benefits of Indole-3-Carbinol in adjuvant-induced arthritis and its protective effect against methotrexate induced-hepatic toxicity. BMC Complement Altern. Med. 2018; 18(1): 337. https://dx.doi.org/10.1186/s12906-018-2408-1.
- Choi Y., Abdelmegeed M.A., Song B.J. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis. J. Nutr. Biochem. 2018; 55: 12-25. https://dx.doi.org/10.1016/j.jnutbio.2017.11.011.
- Сметник А.А., Сметник В.П., Киселев В.И. Опыт применения индол-3-карбинола в лечении заболеваний молочной железы и профилактике рака молочной железы. Акушерство и гинекология. 2017; 2: 106-12. [Smetnik A.A., Smetnik V.P., Kiselev V.I. Experience with indole-3-carbinol used to treat diseases of the breast and to prevent breast cancer. Obstetrics and Gynecology. 2017; (2): 106-12. (in Russian)]. https://dx.doi.org/10.18565/aig.2017.2.106-12.
Supplementary files
