DOI: https://doi.org/10.18370/2309-4117.2020.52.54-60

Polycystic ovary syndrome: approach to correction of metabolic disorders

Л. В. Калугіна, Т. Ф. Татарчук

Abstract


Objective: to study the reliability of working hypothesis about positive effect of plant adaptogens with hepatoprotective and anti-inflammatory activity in correction of metabolic complications of polycystic ovary syndrome (PCOS) and to study the possibility of including schisandrin into treatment, choice of which is due to its properties to improve tissue sensitivity to insulin, hepatoprotective, hypolipidemic, anti-inflammatory and antioxidant effects.

Materials and methods. A comparative prospective study of 60 patients aged 18–38 years with PCOS (phenotype A) was carried out. Criteria for inclusion in the study were: a confirmed diagnosis with increased ovaries and oligo-/anovulation, increased level of ovarian androgens; body mass index (BMI) from 25 to 30.1 kg/m2. All women underwent a general clinical examination evaluating anthropometric parameters and BMI, the presence of clinical manifestations of hyperandrogenism (hirsutism and androgenic dermatopathy) on a Ferriman-Gallwey scale, ultrasound of the genital organs, assessment of progesterone and insulin resistance based on the NOMA index on the 22–24th day of the menstrual cycle. Рatients were divided into 2 equal groups depending on the therapy: women in the main group were prescribed schisandrin 1 tablet (250 mg) three times a day for 12 weeks, patients in the control group received recommendations on diet and physical load.

Results. The resulting course of treatment with schisandrin showed restoration of regular menstrual cycles in 40% of patients (versus 16.6% at the beginning of the study) due to a 1.4-fold increase in progesterone level, improvement of skin condition, BMI normalization. A positive effect of treatment on the metabolic status was also noted: a significant decrease in HOMA indices was observed, and transaminases levels were normalized.

Conclusions. For a comprehensive examination of patients with PCOS, especially those who are overweight and obese, it is necessary to include a HOMA index assessment, functional liver tests, ultrasound of the hepatobiliary system with elastography. Complex therapy regimen should include schisandrin for prevention of metabolic disorders in women with PCOS and overweight.


Keywords


polycystic ovary syndrome; treatment; insulin resistance; steatohepatosis; schisandrin

References


Tatarchuk, T.F., Tutchenko, T.M., Perekhrestenko, O.V., et al. “Metabolic syndrome: what changed during last 30 years?” Reproductive endocrinology 5.43 (2018): 15–27. DOI: 10.18370/2309-4117.2018.43.15-27

Teede, H.J., et al. “Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.” Fertil Steril 110.3 (2018): 364–79. DOI: 10.1016/j.fertnstert.2018.05.004

NIH: Office of Disease Prevention. Polycystic Ovary Syndrome, Pathways to Prevention (2012). Available from: [https://prevention-archive.od.nih.gov/docs/ programs/pcos/FinalReport.pdf].

Lim, S.S., et al. “Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression.” Obesity Reviews 20.2 (2019): 339–52. DOI: 10.1111/obr.12762

Condorelli, R.A., et al. “Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.” Journal of endocrinological investigation 41.4 (2018): 383–8. DOI: 10.1007/s40618-017-0762-3

American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. National Guideline Clearinghouse. Available from: [http://guideline.gov/summary/summary. aspx?doc_id=7108].

Azziz, R. “Polycystic ovary syndrome, reproductive endocrinology and infertility.” Obstet Gynecol 132.2 (2018): 321–36. DOI: 10.1097/AOG.0000000000002698

Olatunbosun, S.T., Griffing, G.T. Medscape, endocrynology, insulin resistance (2017). Available from: [https://emedicine.medscape.com/article/122501-overview#a4].

Adams, L.A., Lymp, J.F., St Sauver, J., et al. “The natural history of nonalcoholic fatty liver disease: a population-based cohort study.” Gastroenterology 129 (2005): 113–21.

Agacayak, E., Tunc, S.Y., Sak, S., et al. “Levels of Neopterin and other Inflammatory Markers in Obese and Non-Obese Patients with Polycystic Ovary Syndrome.” Med Sci Monit 21 (2015): 2446–55.

Laganà, A.S., Vitale, S.G., Noventa, M., Vitagliano, A. “Current management of polycystic ovary syndrome: from bench to bedside.” Int J Endocrinol (2018): 7234543. DOI: 10.1155/2018/7234543

Chernukha, G.E., Udovichenko, M.A., Naidukova, A.A. “The mechanisms of the formation of insulin resistance in polycystic ovary syndrome and therapeutic effects of myo-inositol.” Gynecology 11.166 (2019): 55–60.

Toprak, S., Yönem, A., Akir, B., et al. “Insulin resistance in nonobese patients with polycystic ovary syndrome.” Horm Res 55.2 (2016): 65–70. DOI: 10.1159/000049972

Milewicz, A., Marek, K., Robert, S., Romuald, Z.D “The polycystic ovary syndrome: a position statement from the Polish Society of Endocrinology, the Polish Society of Gynaecologists and Obstetricians, and the Polish Society of Gynaecological Endocrinology.” Endokrynol Pol 69 (2018): 328–36. DOI: 10.5603/EP. 2018.0046

Salva-Pastor, N.C., Chávez-Tapia, N., Uribe, M., et al. “Understanding the association of polycystic ovary syndrome and nonalcoholic fatty liver disease.” Journal of Steroid Biochemistry and Molecular Biology 194 (2019): 105445.

Chalasani, N., Younossi, Z., Lavine, J.E., et al. “The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.” Hepatology 55 (2012): 2005–23.

Goldrat, O., Delbaere, A. “PCOS: update and diagnostic approach.” Clin Biochem 62 (2018): 24–31. DOI: 10.1016/j.clinbiochem.2018.09.001

Mott, M., Kitos, N., Coviello, A. “Practice patterns in screening for metabolic disease in women with PCOS of diverse race-ethnic backgrounds.” Endocr Pract 20 (2014): 855–63. DOI: 10.4158/EP13414.OR

Uspenskaya, Y.B., Kuznetsova, I.V., Vedzizheva, E.R. “Non-alcoholic fatty liver disease in patients with polycystic ovary syndrome.” CONSILIUM MEDICUM 18.6 (2016): 52–8.

Zhang, J., Hu, J., Zhang, C., et al. “Analyses of risk factors forpolycystic ovary syndrome complicated with non-alcoholic fatty liver disease.” Exp Ther Med 15 (2018): 4259–64/ DOI: 10.3892/etm.2018.5932.

Ramezani Binabaj, M., Motalebi, M., Karimi-Sari, H., et al. “Are women with polycystic ovarian syndrome at a high risk of nonalcoholic fatty liver disease? A meta-analysis.” Hepat Mon 14 (2014): 1–7. DOI: 10.5812/hepatmon.23235

Legro, R.S., Arslanian, S.A., Ehrmann, D.A., et al. “Diagnosis and treatment of polycystic ovary syndrome: an endocrinesociety clinical practice guideline.” J Clin Endocrinol Metab 98 (2013): 4565–92. DOI: 10.1210/jc.2013-2350

El-Mazny, A., Abou-Salem, N., El-Sherbiny, W. “Insulin resistance, dyslipidemia, and metabolic syndrome in women with polycystic ovary syndrome.” Int J Gynaecol Obstet 109 (2010): 239–41.

Kadowaki, T., Yamauchi, T., Kubota, N., et al. “Adiponectin and adiponectin receptors ininsulin resistance, diabetes, and the metabolic syndrome.” J Clin Invest 116 (2006): 1784–92.

Economou, F., Xyrafis, X., Livadas, S., et al. “In overweight/obese but not in normal-weight women, polycystic ovary syndrome is associated with elevated liver enzymes compared to controls.” Hormones (Athens) 8 (2009): 199–206.

Lerchbaum, E., Gruber, H.J., Schwetz, V., et al. “Fatty liver index in polycystic ovary syndrome.” Eur J Endocrinol 165 (2011): 935–43.

Chalasani, N., Younossi, Z., Lavine, J.E., et al. “The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Studyof Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.” Hepatology 55 (2012): 2005–23.

Michalakis, K.., Mintziori, G., Kaprara, A. “The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review.” Metabolism 62.4 (2013): 457–78.

O’Brien, S.M., Fitzgerald, P., Scully, P., et al. “Impact of gender and menstrual cycle phase on plasma cytokine concentrations.” Neuroimmunomodulation 14 (2007): 84–90.

Tzanavari, T., Giannogonas, P., Karalis, K.P. “TNF-alpha and obesity.” Curr Dir Autoimmun 11 (2010): 145–56.

Badman, M.K., Flier, J.S. “The adipocyte as an active participant in energy balance and metabolism.” Gastroenterology 132 (2007): 2103–15.

Kitade, H., Chen, G., Ni, Y., et al. “Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments.” Nutrients 9 (2017): 387. DOI: 10.3390/nu9040387

Wensveen, F.M., Jelencic, V., Valentic, S., et al. “NK cells link obesity-induced adipose stress to inflammation and insulin resistance.” Nat Immunol 16 (2015): 376–85.

Mikolasevic, I., Milic, S., Turk, T. “Nonalcoholic fatty liver disease – A multisystem disease?” World J Gastroenterol 22.43 (2016): 9488–505.

Abdelmalek, M.F., Diehl, A.M. “Nonalcoholic fatty liver disease as a complication of insulin resistance.” Med Clin North Am 91 (2007): 1125–49.

Baranova, A., Tran, T.P., Birerdinc, A., Younossi, Z.M. “Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease.” Aliment Pharmacol Ther 33 (2011): 801–4.

Nowak, A., Zakłos-Szyda, M., Błasiak, J., et al. “Potential of Schisandra chinensis (Turcz.) Baill. in Human Health and Nutrition: A Review of Current Knowledge and Therapeutic Perspectives.” Nutrients 11.2 (2019).

Szopa, A., Ekiert, R., Ekiert, H. “Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies.” Phytochem Rev 16.2 (2017): 195–218.

Jang, M.K., Nam, J.S., Kim, J.H., et al. “Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress.” J Ethnopharmacol 185 (2016): 96–104.

Hong, M., Zhang, Y., Li, S., et al. “А Network PharmacologyBased Study on the Hepatoprotective Effect of Fructus Schisandrae.” Molecules 22.10 (2017).

Jeong, M.J., Kim, S.R., Jung, U.J. “Schizandrin A supplementation improves nonalcoholic fatty liver disease in mice fed a high-fat and high-cholesterol diet.” Nutr Res 64 (2019): 64–71.

Fadeenko, G.D., Kolesnikova, O.V., Solomentseva, T.A. “New possibilities of treatment of non-alcoholic steatohepatitis.” Modern gastroenterology 99.1 (2018): 53–60.

Kolesnikova, O.V. “A look at liver fibrosis in the light of understanding the modern mechanisms of its development.” Gastroenterology 2 Vol. 53 (2019): 67–76.

Dorofeev, A.E., Rudenko, N.N., Tkach, S.M., et al. “Type 2 diabetes and non-alcoholic fatty liver disease: new options for therapeutic correction.” Gastroenterology 4 Vol. 53 (2019): 18–25.


GOST Style Citations


1.            Татарчук, Т.Ф. Метаболічний синдром: що змінилось за 30 років? / Т.Ф. Татарчук, Т.М. Тутченко, О.В. Перехрестенко та ін. // Репродуктивна ендокринологія. – 2018. – №5 (43). – С. 15–27.

2.            Teede, H.J., et al. “Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.” Fertil Steril 110.3 (2018): 364–79. DOI: 10.1016/j.fertnstert.2018.05.004

3.            NIH: Office of Disease Prevention. Polycystic Ovary Syndrome, Pathways to Prevention (2012). Available from: [https://prevention-archive.od.nih.gov/docs/ programs/pcos/FinalReport.pdf].

4.            Lim, S.S., et al. “Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression.” Obesity Reviews 20.2 (2019): 339–52. DOI: 10.1111/obr.12762

5.            Condorelli, R.A., et al. “Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.” Journal of endocrinological investigation 41.4 (2018): 383–8. DOI: 10.1007/s40618-017-0762-3

6.            American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. National Guideline Clearinghouse. Available from: [http://guideline.gov/summary/summary. aspx?doc_id=7108].

7.            Azziz, R. “Polycystic ovary syndrome, reproductive endocrinology and infertility.” Obstet Gynecol 132.2 (2018): 321–36. DOI: 10.1097/AOG.0000000000002698

8.            Olatunbosun, S.T., Griffing, G.T. Medscape, endocrynology, insulin resistance (2017). Available from: [https://emedicine.medscape.com/article/122501-overview#a4].

9.            Adams, L.A., Lymp, J.F., St Sauver, J., et al. “The natural history of nonalcoholic fatty liver disease: a population-based cohort study.” Gastroenterology 129 (2005): 113–21.

10.          Agacayak, E., Tunc, S.Y., Sak, S., et al. “Levels of Neopterin and other Inflammatory Markers in Obese and Non-Obese Patients with Polycystic Ovary Syndrome.” Med Sci Monit 21 (2015): 2446–55.

11.          Laganà, A.S., Vitale, S.G., Noventa, M., Vitagliano, A. “Current management of polycystic ovary syndrome: from bench to bedside.” Int J Endocrinol (2018): 7234543. DOI: 10.1155/2018/7234543

12.          Чернуха, Г.Е. Механизмы формирования инсулинорезистентности при синдроме поликистозных яичников и терапевтические эффекты мио-инозитола / Г.Е. Чернуха, М.А. Удовиченко, А.А. Найдукова // Гинекология. – 2019. – № 11 (166). – С. 55–60.

13.          Toprak, S., Yönem, A., Akir, B., et al. “Insulin resistance in nonobese patients with polycystic ovary syndrome.” Horm Res 55.2 (2016): 65–70. DOI: 10.1159/000049972

14.          Milewicz, A., Marek, K., Robert, S., Romuald, Z.D “The polycystic ovary syndrome: a position statement from the Polish Society of Endocrinology, the Polish Society of Gynaecologists and Obstetricians, and the Polish Society of Gynaecological Endocrinology.” Endokrynol Pol 69 (2018): 328–36. DOI: 10.5603/EP. 2018.0046

15.          Salva-Pastor, N.C., Chávez-Tapia, N., Uribe, M., et al. “Understanding the association of polycystic ovary syndrome and nonalcoholic fatty liver disease.” Journal of Steroid Biochemistry and Molecular Biology 194 (2019): 105445.

16.          Chalasani, N., Younossi, Z., Lavine, J.E., et al. “The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.” Hepatology 55 (2012): 2005–23.

17.          Goldrat, O., Delbaere, A. “PCOS: update and diagnostic approach.” Clin Biochem 62 (2018): 24–31. DOI: 10.1016/j.clinbiochem.2018.09.001

18.          Mott, M., Kitos, N., Coviello, A. “Practice patterns in screening for metabolic disease in women with PCOS of diverse race-ethnic backgrounds.” Endocr Pract 20 (2014): 855–63. DOI: 10.4158/EP13414.OR

19.          Успенская, Ю.Б. Неалкогольная жировая болезнь печени у пациенток с синдромом поликистозных яичников / Ю.Б. Успенская, И.В. Кузнецова, Э.Р. Ведзижева // СONSILIUM MEDICUM. – 2016. – № 6, Т. 18. – С. 52–58.

20.          Zhang, J., Hu, J., Zhang, C., et al. “Analyses of risk factors forpolycystic ovary syndrome complicated with non-alcoholic fatty liver disease.” Exp Ther Med 15 (2018): 4259–64/ DOI: 10.3892/etm.2018.5932.

21.          Ramezani Binabaj, M., Motalebi, M., Karimi-Sari, H., et al. “Are women with polycystic ovarian syndrome at a high risk of nonalcoholic fatty liver disease? A meta-analysis.” Hepat Mon 14 (2014): 1–7. DOI: 10.5812/hepatmon.23235

22.          Legro, R.S., Arslanian, S.A., Ehrmann, D.A., et al. “Diagnosis and treatment of polycystic ovary syndrome: an endocrinesociety clinical practice guideline.” J Clin Endocrinol Metab 98 (2013): 4565–92. DOI: 10.1210/jc.2013-2350

23.          El-Mazny, A., Abou-Salem, N., El-Sherbiny, W. “Insulin resistance, dyslipidemia, and metabolic syndrome in women with polycystic ovary syndrome.” Int J Gynaecol Obstet 109 (2010): 239–41.

24.          Kadowaki, T., Yamauchi, T., Kubota, N., et al. “Adiponectin and adiponectin receptors ininsulin resistance, diabetes, and the metabolic syndrome.” J Clin Invest 116 (2006): 1784–92.

25.          Economou, F., Xyrafis, X., Livadas, S., et al. “In overweight/obese but not in normal-weight women, polycystic ovary syndrome is associated with elevated liver enzymes compared to controls.” Hormones (Athens) 8 (2009): 199–206.

26.          Lerchbaum, E., Gruber, H.J., Schwetz, V., et al. “Fatty liver index in polycystic ovary syndrome.” Eur J Endocrinol 165 (2011): 935–43.

27.          Chalasani, N., Younossi, Z., Lavine, J.E., et al. “The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Studyof Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.” Hepatology 55 (2012): 2005–23.

28.          Michalakis, K.., Mintziori, G., Kaprara, A. “The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review.” Metabolism 62.4 (2013): 457–78.

29.          O’Brien, S.M., Fitzgerald, P., Scully, P., et al. “Impact of gender and menstrual cycle phase on plasma cytokine concentrations.” Neuroimmunomodulation 14 (2007): 84–90.

30.          Tzanavari, T., Giannogonas, P., Karalis, K.P. “TNF-alpha and obesity.” Curr Dir Autoimmun 11 (2010): 145–56.

31.          Badman, M.K., Flier, J.S. “The adipocyte as an active participant in energy balance and metabolism.” Gastroenterology 132 (2007): 2103–15.

32.          Kitade, H., Chen, G., Ni, Y., et al. “Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments.” Nutrients 9 (2017): 387. DOI: 10.3390/nu9040387

33.          Wensveen, F.M., Jelencic, V., Valentic, S., et al. “NK cells link obesity-induced adipose stress to inflammation and insulin resistance.” Nat Immunol 16 (2015): 376–85.

34.          Mikolasevic, I., Milic, S., Turk, T. “Nonalcoholic fatty liver disease – A multisystem disease?” World J Gastroenterol 22.43 (2016): 9488–505.

35.          Abdelmalek, M.F., Diehl, A.M. “Nonalcoholic fatty liver disease as a complication of insulin resistance.” Med Clin North Am 91 (2007): 1125–49.

36.          Baranova, A., Tran, T.P., Birerdinc, A., Younossi, Z.M. “Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease.” Aliment Pharmacol Ther 33 (2011): 801–4.

37.          Nowak, A., Zakłos-Szyda, M., Błasiak, J., et al. “Potential of Schisandra chinensis (Turcz.) Baill. in Human Health and Nutrition: A Review of Current Knowledge and Therapeutic Perspectives.” Nutrients 11.2 (2019).

38.          Szopa, A., Ekiert, R., Ekiert, H. “Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies.” Phytochem Rev 16.2 (2017): 195–218.

39.          Jang, M.K., Nam, J.S., Kim, J.H., et al. “Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress.” J Ethnopharmacol 185 (2016): 96–104.

40.          Hong, M., Zhang, Y., Li, S., et al. “А Network PharmacologyBased Study on the Hepatoprotective Effect of Fructus Schisandrae.” Molecules 22.10 (2017).

41.          Jeong, M.J., Kim, S.R., Jung, U.J. “Schizandrin A supplementation improves nonalcoholic fatty liver disease in mice fed a high-fat and high-cholesterol diet.” Nutr Res 64 (2019): 64–71.

42.          Фадєєнко, Г.Д. Нові можливості лікування неалкогольного стеатогепатиту / Г.Д. Фадєєнко, О.В. Колеснікова, Т.А. Соломенцева // Сучасна гастроентерологія. – 2018. – № 99 (1). – С. 53–60.

43.          Колеснікова, О.В. Погляд на фіброз печінки у світлі розуміння сучасних механізмів його розвитку / О.В. Колесникова // Гастроентерологія. – 2019. – Т. 53, № 2. – С. 67–76.

44.          Дорофеев, А.Э. Сахарный диабет 2 типа и неалкогольная жировая болезнь печени: новые возможности терапевтической коррекции / А.Э. Дорофеев, Н.Н. Руденко, С.М. Ткач и др. // Гастроентерологія. – 2019. – Т. 53, № 4. – С. 18–25.





Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2411-1295 (Online), ISSN 2309-4117 (Print)