medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-060medsovet-7446Research ArticleРЕПРОДУКТИВНОЕ ЗДОРОВЬЕ И ВРТREPRODUCTIVE HEALTH AND ARTТаргетная терапия синдрома поликистозных яичниковTarget therapy of polycystic ovary syndromehttps://orcid.org/0000-0002-4478-9133ТурчинецА. И.TurchinetsA. I.

Турчинец Анна Ильинична, аспирант,

117997, Москва, ул. Академика Опарина, д. 4

Anna I. Turchinets, Postgraduate Student,

4, Academician Oparin St., Moscow, 117997

Ponomarevaanna28@gmail.comhttps://orcid.org/0000-0002-3105-5640УвароваЕ. В.UvarovaE. V.

Уварова Елена Витальевна, член-корр. РАН, д.м.н., профессор, заведующий 2-м гинекологическим отделением, 17997, Москва, ул. Академика Опарина, д. 4; 

профессор кафедры акушерства, гинекологии, перинатологии и репродуктологии Института профессионального образования, 119991, Москва, ул. Трубецкая, д. 8, стр. 2;

президент Межрегиональной общественной организации «Объединение детских и подростковых гинекологов»

Elena V. Uvarova, Corr. Member RAS, Dr. Sci.  (Med.), Professor, Head of the 2nd Gynecological Department, 4, Academician Oparin St., Moscow, 117997;

Professor of  the Department of  Obstetrics, Gynecology, Perinatology and Reproductology, Institute of  Professional Education, 8, Bldg. 2, Trubetskaya St., Moscow, 119991; 

President of the Interregional Public Organization “Association of Pediatric and Adolescent Gynecologists”

elena-uvarova@yandex.ruhttps://orcid.org/0000-0002-3195-307XХащенкоЕ. П.KhashchenkoE. P.

Хащенко Елена Петровна, старший научный сотрудник 2-го гинекологического отделения,

117997, Москва, ул. Академика Опарина, д. 4

Elena P. Khashchenko, Senior Researcher, 2nd Gynecological Department,

4, Academician Oparin St., Moscow, 117997

khashchenko_elena@mail.ruhttps://orcid.org/0000-0001-7511-1432КумыковаЗ. Х.KumykovaZ. Kh.

Кумыкова Заира Хасановна, к.м.н., старший научный сотрудник 2-го  гинекологического отделения (гинекологии детского и юношеского возраста),

117997, Москва, ул. Академика Опарина, д. 4

Zaira Kh. Kumykova, Cand. Sci.  (Med.), Senior Researcher, 2nd Gynecological Department  (Gynecology of  Pediatric and Adolescent Age),

4, Academician Oparin St., Moscow, 117997

zai-kumykova@yandex.ruНациональный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. КулаковаРоссияKulakov National Medical Research Center of Obstetrics, Gynecology and PerinatologyRussian FederationНациональный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова; Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияKulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology; Sechenov First Moscow State Medical University (Sechenov University)Russian Federation20231804202305713Copyright © Турчинец А.И., Уварова Е.В., Хащенко Е.П., Кумыкова З.Х., 20232023Турчинец А.И., Уварова Е.В., Хащенко Е.П., Кумыкова З.Х.Turchinets A.I., Uvarova E.V., Khashchenko E.P., Kumykova Z.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7446

Синдром поликистозных яичников (СПЯ) – эндокринная патология, которой страдают до 13% женщин и до 19,6% девочек пубертатного возраста. Ввиду сложности диагностики и особенностей лечения СПЯ у подростков в настоящее время проводится множество исследований с  целью подбора безопасной таргетной терапии для нормализации метаболического и репродуктивного статуса девочек, в том числе находящихся в группе риска СПЯ. Активно публикуются работы, оценивающие эффективность терапии инозитолами при СПЯ, овариальной дисфункции, инсулинорезистентности, гиперандрогении яичникового генеза как у подростков, так и у взрослых женщин, в том числе и в циклах ЭКО. В настоящее время выбор соотношения миоинозитола (МИ) и D-хироинозитола (ДХИ) для терапии СПЯ часто основывается на физиологической пропорции инозитолов в организме (40 : 1), поскольку имеющихся результатов исследований недостаточно, чтобы однозначно определить оптимальное соотношение изомеров. В связи с этим большинство средств на основе инозитола содержат низкую дозировку ДХИ, которой недостаточно для обхода дефектной эпимеразной активности и достижения адекватного уровня ДХИ в яичниках, или не содержат изомер вовсе. Определение оптимального соотношения и дозировки МИ и ДХИ необходимо для долговременной коррекции метаболических, эндокринных и клинических проявлений различных фенотипов СПЯ, поскольку инозитолы являются перспективными и безопасными в терапии гиперандрогении, ожирения и резистентности к инсулину у женщин разных возрастных групп, а также могут эффективно дополнять терапевтическое действие метформина и комбинированных оральных контрацептивов. 

Due to the complexity of the diagnosis and treatment of polycystic ovary syndrome (PCOS) in adolescents, studies are currently underway to select targeted therapy to normalize the metabolic and reproductive status of girls, including those at risk for PCOS. There are a  lot of  researches, that evaluate the  effectiveness of  inositol therapy in  PCOS, ovarian dysfunction, insulin resistance (IR), ovarian hyperandrogenism in both adolescents and adult women, including those in IVF cycles. Currently, the choice of determining the ratio of myo-inositol (MI) and d-chiro-inositol (DCI) for the treatment of PCOS often leads to the physiological proportion of inositols in plasma (40:1), since research results are insufficient to unambiguously confirm it. In this connection, there is a large number of pharmaceuticals without or with a low dosage of DCI, that can’t bypass the defective epimerase activity and achieve an adequate level of DCI in the ovaries. Determination of a fair assessment and dosage of MI/DCI is required for long-term correction of metabolic, endocrinological and clinical manifestations of various PCOS phenotypes. Inositols are promising and safe treatment of hyperandrogenism, obesity, insulin resistance in women of various age groups and can also effectively complement a therapeutic effect of metformin and combined oral contraceptives. 

миоинозитолD-хироинозитолсиндром поликистозных яичниковинсулинорезистентностьгиперандрогенияmyo-inositolD-chiro-inositolpolycystic ovary syndromehyperandrogenisminsulin resistanceReferencesPeña A.S., Codner E., Witchel S. Criteria for Diagnosis of Polycystic Ovary Syndrome during Adolescence: Literature Review. Diagnostics (Basel). 2022;12(8):1931. https://doi.org/10.3390/diagnostics12081931.Peña A.S., Codner E., Witchel S. Criteria for Diagnosis of Polycystic Ovary Syndrome during Adolescence: Literature Review. Diagnostics (Basel). 2022;12(8):1931. https://doi.org/10.3390/diagnostics12081931.Хащенко Е.П., Уварова Е.В., Мамедова Ф.Ш. Фенотипические особенности синдрома поликистозных яичников у девочек подросткового возраста. Репродуктивное здоровье детей и подростков. 2017;(1):37–50. https://doi.org/10.24411/1816-2134-2017-00015.Khaschenko E.P., Uvarova E.V., Mamedova F.Sh. Phenotypic features of polycystic ovary syndrome in adolescent girls. Pediatric and Adolescent Reproductive Health. 2017;(1):37–50. (In Russ.) https://doi.org/10.24411/1816-2134-2017-00015.Tay C.T., Hart R.J., Hickey M., Moran L.J., Earnest A., Doherty D.A. et al. Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood. BMC Med. 2020;18(1):389. https://doi.org/10.1186/s12916-020-01861-x.Tay C.T., Hart R.J., Hickey M., Moran L.J., Earnest A., Doherty D.A. et al. Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood. BMC Med. 2020;18(1):389. https://doi.org/10.1186/s12916-020-01861-x.Khashchenko E., Uvarova E., Vysokikh M., Ivanets T., Krechetova L., Tarasova N. et al. The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents. J Clin Med. 2020;9(6):1831. https://doi.org/10.3390/jcm9061831.Khashchenko E., Uvarova E., Vysokikh M., Ivanets T., Krechetova L., Tarasova N. et al. The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents. J Clin Med. 2020;9(6):1831. https://doi.org/10.3390/jcm9061831.Адамян Л.В., Андреева Е.Н., Абсатарова Ю.С., Григорян О.Р., Дедов И.И., Мельниченко Г.А. и др. Синдром поликистозных яичников: клинические рекомендации. М.; 2021. 57 с. Режим доступа: https://cr.minzdrav.gov.ru/schema/258_2.Adamyan L.V., Andreeva E.N., Absatarova Yu.S., Grigoryan O.R., Dedov I.I., Melnichenko G.A. et al. Polycystic ovary syndrome: clinical guidelines. Moscow; 2021. 57 p. (In Russ.) Available at: https://cr.minzdrav.gov.ru/schema/258_2.Manique M.E.S., Ferreira A.M.A.P. Polycystic Ovary Syndrome in Adolescence: Challenges in Diagnosis and Management. Rev Bras Ginecol Obstet. 2022;44(4):425–433. https://doi.org/10.1055/s-0042-1742292.Manique M.E.S., Ferreira A.M.A.P. Polycystic Ovary Syndrome in Adolescence: Challenges in Diagnosis and Management. Rev Bras Ginecol Obstet. 2022;44(4):425–433. https://doi.org/10.1055/s-0042-1742292.Trent M., Gordon C.M. Diagnosis and Management of Polycystic Ovary Syndrome in Adolescents. Pediatrics. 2020;145(Suppl. 2):S210–S218. https://doi.org/10.1542/peds.2019-2056J.Trent M., Gordon C.M. Diagnosis and Management of Polycystic Ovary Syndrome in Adolescents. Pediatrics. 2020;145(Suppl. 2):S210–S218. https://doi.org/10.1542/peds.2019-2056J.Белова И.С., Хащенко Е.П., Уварова Е.В., Андреева В.О. Психоэмоциональный статус и нарушения пищевого поведения в генезе развития синдрома поликистозных яичников в подростковом возрасте. Репродуктивное здоровье детей и подростков. 2021;17(3):82–93. https://doi.org/10.33029/1816-2134-2021-17-3-82-93.Belova I.S., Khashchenko E.P., Uvarova E.V., Andreeva V.O. Psychoemotional status and eating disorders in the polycystic ovary syndrome pathogenesis among adolescence. Pediatric and Adolescent Reproductive Health. 2021;17(3):82–93. (In Russ.) https://doi.org/10.33029/1816-2134-2021-17-3-82-93.Bhide P., Pundir J., Gudi A., Shah A., Homburg R., Acharya G. The effect of myo-inositol/di-chiro-inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2019;98(10):1235–1244. https://doi.org/10.1111/aogs.13625.Bhide P., Pundir J., Gudi A., Shah A., Homburg R., Acharya G. The effect of myo-inositol/di-chiro-inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2019;98(10):1235–1244. https://doi.org/10.1111/aogs.13625.Kalra B., Kalra S., Sharma J.B. The inositols and polycystic ovary syndrome. Indian J Endocrinol Metab. 2016;20(5):720–724. https://doi.org/10.4103/2230- 8210.189231.Kalra B., Kalra S., Sharma J.B. The inositols and polycystic ovary syndrome. Indian J Endocrinol Metab. 2016;20(5):720–724. https://doi.org/10.4103/2230- 8210.189231.Russo M., Forte G., Montanino Oliva M., Laganà A.S., Unfer V. Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth. Int J Mol Sci. 2021;22(16):8433. https://doi.org/10.3390/ijms22168433.Russo M., Forte G., Montanino Oliva M., Laganà A.S., Unfer V. Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth. Int J Mol Sci. 2021;22(16):8433. https://doi.org/10.3390/ijms22168433.Kamenov Z., Gateva A. Inositols in PCOS. Molecules. 2020;25(23):5566. https://doi.org/10.3390/molecules25235566.Kamenov Z., Gateva A. Inositols in PCOS. Molecules. 2020;25(23):5566. https://doi.org/10.3390/molecules25235566.Cabrera-Cruz H., Oróstica L., Plaza-Parrochia F., Torres-Pinto I., Romero C., Vega M. The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment. Am J Physiol Endocrinol Metab. 2020;318(2):E237–E248. https://doi.org/10.1152/ajpendo.00162.2019.Cabrera-Cruz H., Oróstica L., Plaza-Parrochia F., Torres-Pinto I., Romero C., Vega M. The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment. Am J Physiol Endocrinol Metab. 2020;318(2):E237–E248. https://doi.org/10.1152/ajpendo.00162.2019.Bizzarri M., Fuso A., Dinicola S., Cucina A., Bevilacqua A. Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opin Drug Metab Toxicol. 2016;12(10):1181–1196. https://doi.org/10.1080/17425255.2016.1206887.Bizzarri M., Fuso A., Dinicola S., Cucina A., Bevilacqua A. Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opin Drug Metab Toxicol. 2016;12(10):1181–1196. https://doi.org/10.1080/17425255.2016.1206887.Unfer V., Facchinetti F., Orrù B., Giordani B., Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect. 2017;6(8):647–658. https://doi.org/10.1530/EC-17-0243.Unfer V., Facchinetti F., Orrù B., Giordani B., Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect. 2017;6(8):647–658. https://doi.org/10.1530/EC-17-0243.Unfer V., Nestler J.E., Kamenov Z.A., Prapas N., Facchinetti F. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrinol. 2016:1849162. https://doi.org/10.1155/2016/1849162.Unfer V., Nestler J.E., Kamenov Z.A., Prapas N., Facchinetti F. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrinol. 2016:1849162. https://doi.org/10.1155/2016/1849162.Carlomagno G., Unfer V., Roseff S. The D-chiro-inositol paradox in the ovary. Fertil Steril. 2011;95(8):2515–2516. https://doi.org/10.1016/j.fertnstert.2011.05.027.Carlomagno G., Unfer V., Roseff S. The D-chiro-inositol paradox in the ovary. Fertil Steril. 2011;95(8):2515–2516. https://doi.org/10.1016/j.fertnstert.2011.05.027.Громова О.А., Торшин И.Ю., Уварова Е.В., Тапильская Н.И., Калачева А.Г. Систематический анализ биологических ролей и фармакологических свойств D-хироинозитола. Гинекология. 2020;22(3):21–28. https://doi.org/10.26442/20795696.2020.3.200210.Gromova O.A., Torshin I.Yu., Uvarova E.V., Tapilskaya N.I., Kalacheva A.G. Systematic analysis of the biological roles and pharmacological properties of D-chiro-inositol. Gynecology. 2020;22(3):21–28. (In Russ.) https://doi.org/10.26442/20795696.2020.3.200210.Доброхотова Ю.Э., Громова О.А., Духанин А.С., Кумыкова З.Х., Шереметьева Е.В., Табеева Г.И. Инозитолы: фармакология и данные клинических исследований. Современное состояние вопроса и перспективы. РМЖ. Мать и дитя. 2022;5(4):309–319. https://doi.org/10.32364/2618-8430-2022-5-4-309-319.Dobrokhotova Yu.E., Gromova O.A., Dukhanin A.S., Kumykova Z.Kh., Sheremetyeva E.V., Tabeeva G.I. Inositols: pharmacology and findings of clinical trials. Current evidence and prospects. Russian Journal of Woman and Child Health. 2022;5(4):309–319 (In Russ.) https://doi.org/10.32364/2618-8430-2022-5-4-309-319.Facchinetti F., Orrù B., Grandi G., Unfer V. Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials. Gynecol Endocrinol. 2019;35(3):198–206. https://doi.org/10.1080/09513590.2018.1540578.Facchinetti F., Orrù B., Grandi G., Unfer V. Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials. Gynecol Endocrinol. 2019;35(3):198–206. https://doi.org/10.1080/09513590.2018.1540578.Goodarzi M.O., Korenman S.G. The importance of insulin resistance in polycystic ovary syndrome. Fertil Steril. 2003;80(2):255–258. https://doi.org/10.1016/s0015-0282(03)00734-9.Goodarzi M.O., Korenman S.G. The importance of insulin resistance in polycystic ovary syndrome. Fertil Steril. 2003;80(2):255–258. https://doi.org/10.1016/s0015-0282(03)00734-9.Прилуцкая В.Ю., Аляутдина О.С., Сосна Н.А. Влияние комбинации миоинозитола и D-хироинозитола в соотношении 5:1 на психоэмоциональное состояние и проявления андрогензависимой дермопатии у пациенток с синдромом поликистозных яичников. Проблемы репродукции. 2021;27(4):97–107. https://doi.org/10.17116/repro20212704197.Prilutskaya V.Yu., Alyautdina O.S., Sosna N.A. The effect of the combination of myoinositol and D-chiroinositol in a ratio of 5:1 on the psychoemotional state and manifestations of androgen-dependent dermopathy in patients with polycystic ovary syndrome. Russian Journal of Human Reproduction. 2021;27(4):97–107. (In Russ.) https://doi.org/10.17116/repro20212704197.Akbari Sene A., Tabatabaie A., Nikniaz H., Alizadeh A., Sheibani K., Mortezapour Alisaraie M. et al. The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial. Arch Gynecol Obstet. 2019;299(6):1701–1707. https://doi.org/10.1007/s00404-019-05111-1.Akbari Sene A., Tabatabaie A., Nikniaz H., Alizadeh A., Sheibani K., Mortezapour Alisaraie M. et al. The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial. Arch Gynecol Obstet. 2019;299(6):1701–1707. https://doi.org/10.1007/s00404-019-05111-1.Showell M.G., Mackenzie-Proctor R., Jordan V., Hodgson R., Farquhar C. Inositol for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018;12(12):CD012378. https://doi.org/10.1002/14651858.CD012378.pub2.Showell M.G., Mackenzie-Proctor R., Jordan V., Hodgson R., Farquhar C. Inositol for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018;12(12):CD012378. https://doi.org/10.1002/14651858.CD012378.pub2.Vartanyan E.V., Tsaturova K.A., Devyatova E.A., Mikhaylyukova A.S., Levin V.A., Petuhova N.L. et al. Improvement in quality of oocytes in polycystic ovarian syndrome in programs of in vitro fertilization. Gynecol Endocrinol. 2017;33(Suppl. 1):8–11. https://doi.org/10.1080/09513590.2017.1399699.Vartanyan E.V., Tsaturova K.A., Devyatova E.A., Mikhaylyukova A.S., Levin V.A., Petuhova N.L. et al. Improvement in quality of oocytes in polycystic ovarian syndrome in programs of in vitro fertilization. Gynecol Endocrinol. 2017;33(Suppl. 1):8–11. https://doi.org/10.1080/09513590.2017.1399699.Regidor P.A., Schindler A.E., Lesoine B., Druckman R. Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Horm Mol Biol Clin Investig. 2018;34(2):2017-0067. https://doi.org/10.1515/hmbci-2017-0067.Regidor P.A., Schindler A.E., Lesoine B., Druckman R. Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Horm Mol Biol Clin Investig. 2018;34(2):2017-0067. https://doi.org/10.1515/hmbci-2017-0067.Ciotta L., Stracquadanio M., Pagano I., Carbonaro A., Palumbo M., Gulino F. Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci. 2011;15(5):509–514. Available at: https://www.europeanreview.org/wp/wp-content/uploads/938.pdf.Ciotta L., Stracquadanio M., Pagano I., Carbonaro A., Palumbo M., Gulino F. Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci. 2011;15(5):509–514. Available at: https://www.europeanreview.org/wp/wp-content/uploads/938.pdf.Brusco G.F., Mariani M. Inositol: effects on oocyte quality in patients undergoing ICSI. An open study. Eur Rev Med Pharmacol Sci. 2013;17(22):3095–3102. Available at: https://www.europeanreview.org/wp/wp-content/uploads/3095-3102.pdf.Brusco G.F., Mariani M. Inositol: effects on oocyte quality in patients undergoing ICSI. An open study. Eur Rev Med Pharmacol Sci. 2013;17(22):3095–3102. Available at: https://www.europeanreview.org/wp/wp-content/uploads/3095-3102.pdf.Deo S., Pandey K., Kumari P., Deo N. Effectiveness of Myo-Inositol and Combined Oral Contraceptives in Adolescent and Young Women with PCOS. SSR Inst Int J Life Sci. 2021;7(2):2763–2773. https://doi.org/10.21276/SSR-IIJLS.2021.7.2.1.Deo S., Pandey K., Kumari P., Deo N. Effectiveness of Myo-Inositol and Combined Oral Contraceptives in Adolescent and Young Women with PCOS. SSR Inst Int J Life Sci. 2021;7(2):2763–2773. https://doi.org/10.21276/SSR-IIJLS.2021.7.2.1.Pkhaladze L., Barbakadze L., Kvashilava N. Myo-Inositol in the Treatment of Teenagers Affected by PCOS. Int J Endocrinol. 2016;2016:1473612. https://doi.org/10.1155/2016/1473612.Pkhaladze L., Barbakadze L., Kvashilava N. Myo-Inositol in the Treatment of Teenagers Affected by PCOS. Int J Endocrinol. 2016;2016:1473612. https://doi.org/10.1155/2016/1473612.Greff D., Juhász A.E., Váncsa S., Váradi A., Sipos Z., Szinte J. et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10. https://doi.org/10.1186/s12958-023-01055-z.Greff D., Juhász A.E., Váncsa S., Váradi A., Sipos Z., Szinte J. et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10. https://doi.org/10.1186/s12958-023-01055-z.Larner J. D-chiro-inositol its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47–60. https://doi.org/10.1080/15604280212528.Larner J. D-chiro-inositol its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47–60. https://doi.org/10.1080/15604280212528.Artini P.G., Di Berardino O.M., Papini F., Genazzani A.D., Simi G., Ruggiero M., Cela V. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013;29(4):375–379. https://doi.org/10.3109/09513590.2012.743020.Artini P.G., Di Berardino O.M., Papini F., Genazzani A.D., Simi G., Ruggiero M., Cela V. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013;29(4):375–379. https://doi.org/10.3109/09513590.2012.743020.La Marca A., Grisendi V., Dondi G., Sighinolfi G., Cianci A. The menstrual cycle regularization following D-chiro-inositol treatment in PCOS women: a retrospective study. Gynecol Endocrinol. 2015;31(1):52–56. https://doi.org/10.3109/09513590.2014.964201.La Marca A., Grisendi V., Dondi G., Sighinolfi G., Cianci A. The menstrual cycle regularization following D-chiro-inositol treatment in PCOS women: a retrospective study. Gynecol Endocrinol. 2015;31(1):52–56. https://doi.org/10.3109/09513590.2014.964201.Piomboni P., Focarelli R., Capaldo A., Stendardi A., Cappelli V., Cianci A. et al. Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin. J Assist Reprod Genet. 2014;31(10):1269–1276. https://doi.org/10.1007/s10815-014-0307-z.Piomboni P., Focarelli R., Capaldo A., Stendardi A., Cappelli V., Cianci A. et al. Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin. J Assist Reprod Genet. 2014;31(10):1269–1276. https://doi.org/10.1007/s10815-014-0307-z.Ashraf A., Kundi M.B., Arif S.U., Asif M., Ilyas M., Rehan H. Analysis of D-Chiro inositol in lowering androgen levels in PCOS patients. Research Square. 2022. https://doi.org/10.21203/rs.3.rs-1329990/v1.Ashraf A., Kundi M.B., Arif S.U., Asif M., Ilyas M., Rehan H. Analysis of D-Chiro inositol in lowering androgen levels in PCOS patients. Research Square. 2022. https://doi.org/10.21203/rs.3.rs-1329990/v1.Laganà A.S., Barbaro L., Pizzo A. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol. Arch Gynecol Obstet. 2015;291(5):1181–1186. https://doi.org/10.1007/s00404-014-3552-6.Laganà A.S., Barbaro L., Pizzo A. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol. Arch Gynecol Obstet. 2015;291(5):1181–1186. https://doi.org/10.1007/s00404-014-3552-6.Nordio M., Bezerra Espinola M.S., Bilotta G., Capoccia E., Montanino Oliva M. Long-Lasting Therapies with High Doses of D-chiro-inositol: The Downside. J Clin Med. 2023;12(1):390. https://doi.org/10.3390/jcm12010390.Nordio M., Bezerra Espinola M.S., Bilotta G., Capoccia E., Montanino Oliva M. Long-Lasting Therapies with High Doses of D-chiro-inositol: The Downside. J Clin Med. 2023;12(1):390. https://doi.org/10.3390/jcm12010390.Minozzi M., D’Andrea G., Unfer V. Treatment of hirsutism with myo-inositol: a prospective clinical study. Reprod Biomed Online. 2008;17(4):579–582. https://doi.org/10.1016/s1472-6483(10)60248-9.Minozzi M., D’Andrea G., Unfer V. Treatment of hirsutism with myo-inositol: a prospective clinical study. Reprod Biomed Online. 2008;17(4):579–582. https://doi.org/10.1016/s1472-6483(10)60248-9.Thalamati S. A comparative study of combination of Myo-inositol and D-chiroinositol versus Metformin in the management of polycystic ovary syndrome in obese women with infertility. Int J Reprod Contracept Obstet Gynecol. 2019;8(3):825–829. https://doi.org/10.18203/2320-1770.ijrcog20190498.Thalamati S. A comparative study of combination of Myo-inositol and D-chiroinositol versus Metformin in the management of polycystic ovary syndrome in obese women with infertility. Int J Reprod Contracept Obstet Gynecol. 2019;8(3):825–829. https://doi.org/10.18203/2320-1770.ijrcog20190498.Baillargeon J.P., Iuorno M.J., Jakubowicz D.J., Apridonidze T., He N., Nestler J.E. Metformin therapy increases insulin-stimulated release of D-chiro-inositolcontaining inositolphosphoglycan mediator in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(1):242–249. https://doi.org/10.1210/jc.2003-030437.Baillargeon J.P., Iuorno M.J., Jakubowicz D.J., Apridonidze T., He N., Nestler J.E. Metformin therapy increases insulin-stimulated release of D-chiro-inositolcontaining inositolphosphoglycan mediator in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(1):242–249. https://doi.org/10.1210/jc.2003-030437.Nordio M., Proietti E. The combined therapy with myo-inositol and D-chiroinositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci. 2012;16(5):575–581. Available at: https://www.europeanreview.org/wp/wp-content/uploads/1357.pdf.Nordio M., Proietti E. The combined therapy with myo-inositol and D-chiroinositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci. 2012;16(5):575–581. Available at: https://www.europeanreview.org/wp/wp-content/uploads/1357.pdf.Minozzi M., Nordio M., Pajalich R. The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. Eur Rev Med Pharmacol Sci. 2013;17(4):537–540. Available at: https://www.europeanreview.org/wp/ wp-content/uploads/537-540.pdf.Minozzi M., Nordio M., Pajalich R. The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. Eur Rev Med Pharmacol Sci. 2013;17(4):537–540. Available at: https://www.europeanreview.org/wp/ wp-content/uploads/537-540.pdf.Colazingari S., Treglia M., Najjar R., Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet. 2013;288(6):1405–1411. https://doi.org/10.1007/s00404-013-2855-3.Colazingari S., Treglia M., Najjar R., Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet. 2013;288(6):1405–1411. https://doi.org/10.1007/s00404-013-2855-3.Januszewski M., Issat T., Jakimiuk A.A., Santor-Zaczynska M., Jakimiuk A.J. Metabolic and hormonal effects of a combined Myo-inositol and d-chiroinositol therapy on patients with polycystic ovary syndrome (PCOS). Ginekol Pol. 2019;90(1):7–10. https://doi.org/10.5603/GP.2019.0002.Januszewski M., Issat T., Jakimiuk A.A., Santor-Zaczynska M., Jakimiuk A.J. Metabolic and hormonal effects of a combined Myo-inositol and d-chiroinositol therapy on patients with polycystic ovary syndrome (PCOS). Ginekol Pol. 2019;90(1):7–10. https://doi.org/10.5603/GP.2019.0002.Mendoza N., Diaz-Ropero M.P., Aragon M., Maldonado V., Llaneza P., Lorente J. et al. Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol. 2019;35(8):695–700. https://doi.org/10.1080/09513590.2019.1576620.Mendoza N., Diaz-Ropero M.P., Aragon M., Maldonado V., Llaneza P., Lorente J. et al. Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol. 2019;35(8):695–700. https://doi.org/10.1080/09513590.2019.1576620.Mendoza N., Galan M.I., Molina C., Mendoza-Tesarik R., Conde C., Mazheika M. et al. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol. 2020;36(5):398–401. https://doi.org/10.1080/09513590.2019.1681959.Mendoza N., Galan M.I., Molina C., Mendoza-Tesarik R., Conde C., Mazheika M. et al. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol. 2020;36(5):398–401. https://doi.org/10.1080/09513590.2019.1681959.

The authors declare that there are no conflicts of interest present.