DOI: https://doi.org/10.18370/2309-4117.2020.54.89-94

Polycystic ovary syndrome: individualized approach to treatment. Literature review

Л. А. Жабіцька

Abstract


Polycystic ovary syndrome (PCOS) is one of the most common causes of hyperandrogenism, menstrual irregularity and cardiometabolic dysfunction in women. The complete clinical picture includes irregular menstrual cycle, hirsutism, obesity, insulin resistance and anovulatory infertility. This article highlights the main issues for the PCOS definition, emphasizing its phenotypic heterogeneity. The main diagnostic criteria are given, which in turn determine the different phenotypes of this syndrome.

To date, in order to improve the diagnosis and treatment of this syndrome, four different phenotypes have been identified, which include certain combinations of diagnostic criteria: 1) hyperandrogenism (clinical or biochemical) and chronic anovulation; 2) hyperandrogenism and polycystic ovaries on ultrasound, but with ovulatory cycles; 3) chronic anovulation and polycystic ovaries without hyperandrogenemia; 4) hyperandrogenemia, chronic anovulation and polycystic ovaries.

This article presents the main groups of drugs that should be used in treatment of this pathology, according to the latest international guidelines, systematic reviews and meta-analyzes. In particular, indicated application features of insulin sensitizers and other antidiabetic drugs, glucagon-like peptide-1 analogues, oral contraceptives and progestins, antiandrogens. Particular attention is paid to the treatment choice depending on the phenotype and individual needs of patient. Therapeutic approach to the metabolic, hyperandrogenic and reproductive phenotype is covered separately.

Anovulation or infrequent ovulation is a major cause of reproductive dysfunction in women with PCOS. The article lists the main methods and drugs that should be used to induce ovulation. In particular, the features of ovulation induction in women with clomiphene-resistance are considered. The cornerstone of treatment of women with PCOS and obesity with abdominal phenotype is a lifestyle modification, including diet and exercises. The clinical recommendations given in the article are based on the principles of evidence-based medicine

Keywords


polycystic ovary syndrome; hyperandrogenism; anovulation; obesity; treatment; antiandrogens

References


The American College of Obstetricians and Gynecologists. “ACOG Practice Bulletin №194: Polycystic Ovary Syndrome.” Obstet Gynecol 131.6 (2018): 157–71.

Azziz, R. Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults (2019). Available from: [https://www. uptodate.com/contents/epidemiology-phenotype-and-genetics-of-the-polycystic-ovary-syndrome-in-adults], last accessed Aug 17, 2020.

Azziz, R., Carmina, E., Dewailly, D., et al. “The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report.” Fertil Steril 91 (2009): 456–88.

Baillargeon, J.P., Jakubowicz, D.J., Iuorno, M.J., et al. “Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.” Fertil Steril 82 (2004): 893.

Barbieri, R.L., Ehrmann, D.A. Clinical manifestations of polycystic ovary syndrome in adults (2020). Available from: [https://www.uptodate.com/contents/clinical-manifestations-of-polycystic-ovary-syndrome-in-adults], last accessed Aug 17, 2020.

Barbieri, R.L., Ehrmann, D.A. Metformin for treatment of the polycystic ovary syndrome (2018). Available from: [https://www.uptodate.com/contents/metformin-for-treatment-of-the-polycystic-ovary-syndrome], last accessed Aug 17, 2020.

Barbieri, R.L., Chang, J. Treatment of hirsutism (2017). Available from: [https://www. uptodate.com/contents/treatment-of-hirsutism], last accessed Aug 17, 2020.

Barbieri, R.L., Ehrmann, D.A. Treatment of polycystic ovary syndrome in adults (2017). Available from: [https://www.uptodate.com/contents/treatment-of-polycystic-ovary-syndrome-in-adults], last accessed Aug 17, 2020.

Barrionuevo, P., Nabhan, M., Altayar, O., et al. “Treatment Options for Hirsutism: A Systematic Review and Network Meta-Analysis.” J Clin Endocrinol Metab 103 (2018): 1258.

Bartz, A.D., Roe, A., Douglas, P.S. Combined estrogen-progestin contraception: Side effects and health concerns (2019). Available from: [https://www. uptodate.com/contents/combined-estrogen-progestin-contraception-side-effects-and-health-concerns], last accessed Aug 17, 2020.

Bird, S.T., Hartzema, A.G., Brophy, J.M., et al. “Risk of venous thromboembolism in women with polycystic ovary syndrome: a population - based matched cohort analysis.” Canadian Medical Association Journal 185 (2013): 115–20.

Bhattacharya, S.M., Jha, A. “Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome.” Fertil Steril 98 (2012): 1053–9.

Casper, R.F., Mitwally, M.F. Ovulation induction with letrozole (2018). Available from: [https://www.uptodate.com/contents/ovulation-induction-with-letrozole], last accessed Aug 17, 2020.

Deswal, R., Nanda, S., Dang, A.S. “Single Nucleotide Polymorphisms in Treatment of Polycystic Ovary Syndrome: A Systematic Review.” Drug Metab Rev 51.4 (2019): 612–22.

Diamanti-Kandarakis, E., Christakou, C.D., Kandaraki, E., Economou, F.N. “Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome.” European Journal of Endocrinology 162 (2010): 193–212.

Domecq, J.P., Prutsky, G., Mullan, R.J., et al. “Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis.” Journal of Clinical Endocrinology and Metabolism 98 (2013): 4655–63.

Duleba, A.J. “Medical management of metabolic dysfunction in PCOS.” Steroids 77 (2012): 306–11.

Escobar-Morreale, H.F., Carmina, E., Dewailly, D., et al. “Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society.” Human Reproduction Update 18 (2012): 146–70.

Farquhar, C., Lilford, R.J., Marjoribanks, J., Vandekerckhove, P. “Laparoscopic ‘drilling’ by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.” Cochrane Database Syst Rev (2007).

Fauser, B.C., Tarlatzis, B.C., Rebar, R.W., et al. “Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group.” Fertil Steril 97 (2012): 28–38.

Gambineri, A., Patton, L., Vaccina, A., еt al. “Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-14 month, placebo-controlled study.” Journal of Clinical Endocrinology and Metabolism 91 (2006): 3970–80.

Gourdy, P. “Diabetes and oral contraception.” Best Practice & Research. Clinical Endocrinology & Metabolism 27 (2013): 67–76.

Jones, M.R., Goodarzi, M.O. “Genetic Determinants of Polycystic Ovary Syndrome: Progress and Future Directions.” Fertil Steril 106.1 (2016): 25–32.

Legro, R.S., Arslanian, S.A., Ehrmann, D.A., et al. “Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline.” Journal of Clinical Endocrinology and Metabolism 98 (2013): 4565–92.

Lizneva, D., Suturina, L., Walker, W., et al. “Criteria, Prevalence, and Phenotypes of Polycystic Ovary Syndrome.” Fertil Steril 106.1 (2016): 6–15.

Mazza, A., Fruci, B., Guzzi, P.D., et al. “In PCOS patients the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism than metformin alone.” Nutrition, Metabolism, and Cardiovascular Diseases 24 (2014): 132–9.

McCartney, C.R., Marshall, J.C. “Clinical practice. Polycystic Ovary Syndrome.” NEngl J Med 375.1 (2016): 54–64.

McLuskie, I., Newth, A. “New Diagnosis of Polycystic Ovary Syndrome.” BMJ 356 (2017): 6456.

Meier, R.K. “Polycystic Ovary Syndrome.” Nurs Clin North Am 53.3 (2018): 407–20.

Moghetti, P. “Insulin Resistance and Polycystic Ovary Syndrome.” Curr Pharm Des 22.36 (2016): 5526–34.

Nandi, A., Chen, Z., Patel, R., Poretsky, L. “Polycystic Ovary Syndrome.” Endocrinol Metab Clin North Am 43.1 (2014): 123–47.

Neven, A., Laven, J., Teede, H.J., Boyle, J.A. “A Summary on Polycystic Ovary Syndrome: Diagnostic Criteria, Prevalence, Clinical Manifestations, and Management According to the Latest International Guidelines.” Semin Reprod Med 36.1 (2018): 5–12.

Nissen, S.E., Wolski, K. “Rosiglitazone revisited: an updated meta- analysis of risk for myocardial infarction and cardiovascular mortality.” Archives of Internal Medicine 170 (2010): 1191–1201.

Papalou, O., Victor, V.M., Diamanti-Kandarakis, E. “Oxidative Stress in Polycystic Ovary Syndrome.” Curr Pharm Des 22.18 (2016): 2709–22.

Pasquali, R., Gambineri, A. “Therapy in endocrine disease: treatment of hirsutism in the polycystic ovary syndrome.” European Journal of Endocrinology 170 (2013): 75–90.

Rausch, M.E., Legro, R.S., Barnhart, H.X., et al. “Predictors of pregnancy in women with polycystic ovary syndrome.” Journal of Clinical Endocrinology and Metabolism 94 (2009): 3458–66.

Rothenberg, S.S., Beverley, R., Barnard, E., et al. “Polycystic Ovary Syndrome in Adolescents.” Best Pract Res Clin Obstet Gynaecol 48 (2018): 103–114.

The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. “Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).” Human Reproduction 19 (2004): 41–7.

Tomlinson, J., Pinkney, J., Adams, L., et al. “The Diagnosis and Lived Experience of Polycystic Ovary Syndrome: A Qualitative Study.” J Adv Nurs 73.10 (2017): 2318–26.

Stein, I.F., Leventhal, M.L. “Amenorrhea associated with bilateral polycystic ovaries.” American Journal of Obstetrics and Gynecology 29 (1935): 181.

Vilsboll, T., Christensen, M., Junker, A.E., et al. “Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials.” BMJ 344 (2012): 7771–15.


GOST Style Citations


1.      The American College of Obstetricians and Gynecologists. “ACOG Practice Bulletin №194: Polycystic Ovary Syndrome.” Obstet Gynecol 131.6 (2018): 157–71.

2.      Azziz, R. Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults (2019). Available from: [https://www. uptodate.com/contents/epidemiology-phenotype-and-genetics-of-the-polycystic-ovary-syndrome-in-adults], last accessed Aug 17, 2020.

3.      Azziz, R., Carmina, E., Dewailly, D., et al. “The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report.” Fertil Steril 91 (2009): 456–88.

4.      Baillargeon, J.P., Jakubowicz, D.J., Iuorno, M.J., et al. “Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.” Fertil Steril 82 (2004): 893.

5.      Barbieri, R.L., Ehrmann, D.A. Clinical manifestations of polycystic ovary syndrome in adults (2020). Available from: [https://www.uptodate.com/contents/clinical-manifestations-of-polycystic-ovary-syndrome-in-adults], last accessed Aug 17, 2020.

6.      Barbieri, R.L., Ehrmann, D.A. Metformin for treatment of the polycystic ovary syndrome (2018). Available from: [https://www.uptodate.com/contents/metformin-for-treatment-of-the-polycystic-ovary-syndrome], last accessed Aug 17, 2020.

7.      Barbieri, R.L., Chang, J. Treatment of hirsutism (2017). Available from: [https://www. uptodate.com/contents/treatment-of-hirsutism], last accessed Aug 17, 2020.

8.      Barbieri, R.L., Ehrmann, D.A. Treatment of polycystic ovary syndrome in adults (2017). Available from: [https://www.uptodate.com/contents/treatment-of-polycystic-ovary-syndrome-in-adults], last accessed Aug 17, 2020.

9.      Barrionuevo, P., Nabhan, M., Altayar, O., et al. “Treatment Options for Hirsutism: A Systematic Review and Network Meta-Analysis.” J Clin Endocrinol Metab 103 (2018): 1258.

10.    Bartz, A.D., Roe, A., Douglas, P.S. Combined estrogen-progestin contraception: Side effects and health concerns (2019). Available from: [https://www. uptodate.com/contents/combined-estrogen-progestin-contraception-side-effects-and-health-concerns], last accessed Aug 17, 2020.

11.    Bird, S.T., Hartzema, A.G., Brophy, J.M., et al. “Risk of venous thromboembolism in women with polycystic ovary syndrome: a population - based matched cohort analysis.” Canadian Medical Association Journal 185 (2013): 115–20.

12.    Bhattacharya, S.M., Jha, A. “Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome.” Fertil Steril 98 (2012): 1053–9.

13.    Casper, R.F., Mitwally, M.F. Ovulation induction with letrozole (2018). Available from: [https://www.uptodate.com/contents/ovulation-induction-with-letrozole], last accessed Aug 17, 2020.

14.    Deswal, R., Nanda, S., Dang, A.S. “Single Nucleotide Polymorphisms in Treatment of Polycystic Ovary Syndrome: A Systematic Review.” Drug Metab Rev 51.4 (2019): 612–22.

15.    Diamanti-Kandarakis, E., Christakou, C.D., Kandaraki, E., Economou, F.N. “Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome.” European Journal of Endocrinology 162 (2010): 193–212.

16.    Domecq, J.P., Prutsky, G., Mullan, R.J., et al. “Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis.” Journal of Clinical Endocrinology and Metabolism 98 (2013): 4655–63.

17.    Duleba, A.J. “Medical management of metabolic dysfunction in PCOS.” Steroids 77 (2012): 306–11.

18.    Escobar-Morreale, H.F., Carmina, E., Dewailly, D., et al. “Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society.” Human Reproduction Update 18 (2012): 146–70.

19.    Farquhar, C., Lilford, R.J., Marjoribanks, J., Vandekerckhove, P. “Laparoscopic ‘drilling’ by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.” Cochrane Database Syst Rev (2007).

20.    Fauser, B.C., Tarlatzis, B.C., Rebar, R.W., et al. “Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group.” Fertil Steril 97 (2012): 28–38.

21.    Gambineri, A., Patton, L., Vaccina, A., еt al. “Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-14 month, placebo-controlled study.” Journal of Clinical Endocrinology and Metabolism 91 (2006): 3970–80.

22.    Gourdy, P. “Diabetes and oral contraception.” Best Practice & Research. Clinical Endocrinology & Metabolism 27 (2013): 67–76.

23.    Jones, M.R., Goodarzi, M.O. “Genetic Determinants of Polycystic Ovary Syndrome: Progress and Future Directions.” Fertil Steril 106.1 (2016): 25–32.

24.    Legro, R.S., Arslanian, S.A., Ehrmann, D.A., et al. “Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline.” Journal of Clinical Endocrinology and Metabolism 98 (2013): 4565–92.

25.    Lizneva, D., Suturina, L., Walker, W., et al. “Criteria, Prevalence, and Phenotypes of Polycystic Ovary Syndrome.” Fertil Steril 106.1 (2016): 6–15.

26.    Mazza, A., Fruci, B., Guzzi, P.D., et al. “In PCOS patients the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism than metformin alone.” Nutrition, Metabolism, and Cardiovascular Diseases 24 (2014): 132–9.

27.    McCartney, C.R., Marshall, J.C. “Clinical practice. Polycystic Ovary Syndrome.” NEngl J Med 375.1 (2016): 54–64.

28.    McLuskie, I., Newth, A. “New Diagnosis of Polycystic Ovary Syndrome.” BMJ 356 (2017): 6456.

29.    Meier, R.K. “Polycystic Ovary Syndrome.” Nurs Clin North Am 53.3 (2018): 407–20.

30.    Moghetti, P. “Insulin Resistance and Polycystic Ovary Syndrome.” Curr Pharm Des 22.36 (2016): 5526–34.

31.    Nandi, A., Chen, Z., Patel, R., Poretsky, L. “Polycystic Ovary Syndrome.” Endocrinol Metab Clin North Am 43.1 (2014): 123–47.

32.    Neven, A., Laven, J., Teede, H.J., Boyle, J.A. “A Summary on Polycystic Ovary Syndrome: Diagnostic Criteria, Prevalence, Clinical Manifestations, and Management According to the Latest International Guidelines.” Semin Reprod Med 36.1 (2018): 5–12.

33.    Nissen, S.E., Wolski, K. “Rosiglitazone revisited: an updated meta- analysis of risk for myocardial infarction and cardiovascular mortality.” Archives of Internal Medicine 170 (2010): 1191–1201.

34.    Papalou, O., Victor, V.M., Diamanti-Kandarakis, E. “Oxidative Stress in Polycystic Ovary Syndrome.” Curr Pharm Des 22.18 (2016): 2709–22.

35.    Pasquali, R., Gambineri, A. “Therapy in endocrine disease: treatment of hirsutism in the polycystic ovary syndrome.” European Journal of Endocrinology 170 (2013): 75–90.

36.    Rausch, M.E., Legro, R.S., Barnhart, H.X., et al. “Predictors of pregnancy in women with polycystic ovary syndrome.” Journal of Clinical Endocrinology and Metabolism 94 (2009): 3458–66.

37.    Rothenberg, S.S., Beverley, R., Barnard, E., et al. “Polycystic Ovary Syndrome in Adolescents.” Best Pract Res Clin Obstet Gynaecol 48 (2018): 103–114.

38.    The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. “Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).” Human Reproduction 19 (2004): 41–7.

39.    Tomlinson, J., Pinkney, J., Adams, L., et al. “The Diagnosis and Lived Experience of Polycystic Ovary Syndrome: A Qualitative Study.” J Adv Nurs 73.10 (2017): 2318–26.

40.    Stein, I.F., Leventhal, M.L. “Amenorrhea associated with bilateral polycystic ovaries.” American Journal of Obstetrics and Gynecology 29 (1935): 181.

41.    Vilsboll, T., Christensen, M., Junker, A.E., et al. “Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials.” BMJ 344 (2012): 7771–15.





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