Keywords
insulin reistance
ovulation
polycystic ovary syndrome
procreative health
How to Cite
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders and causes of infertility in women in reproductive age. Diagnostic criteria of PCOS in adult women include: ovulation disorders, hyperandrogenism and polycystic ovaries. According to most recommendations, 2 out of these 3 criteria are confirm the diagnosis of PCOS. In girls during puberty and in the first years after menarche, different diagnostic criteria of menstrual disorders should be taken into account (variable length of menstrual cycles, monophasic cycles) and the limited usefulness of ultrasound examination for PCOS diagnosis within 8 years after menarche. Fairly extensive differential diagnosis is also necessary, especially – exclusion of adrenal hyperandrogenism. Moreover, the diagnostic criteria of PCOS do not take into account the metabolic disorders found in most patients (obesity, insulin resistance, type 2 diabetes), which should be diagnosed as early as possible and treated appropriately. This is especially true for teenagers, in whom the unequivocal diagnosis of PCOS or its exclusion may be very difficult. Current recommendations regard hormonal contraception as the first-line therapy in PCOS, in both adult women and adolescents. Together with its beneficial effect on the reduction of hyperandrogenism and obtaining regular bleeding (which in fact are not menstruations), the unfavorable metabolic effects of hormonal contraception are emphasized, as well as the inadequacy of its use if it is expected to achieve or restore ovulation and fertility. The latest reports indicate the legitimacy of treatment aimed at correcting disorders of carbohydrate metabolism and its greater effectiveness compared to the use of oral contraceptives in both adult women and girls with PCOS. In the pharmacotherapy of insulin resistance, metformin is of fundamental importance, the use of pioglitazone, GLP-1 receptor agonists or inositols is also proposed. Adequate lifestyle and dietary modification are of major importance in the treatment and prevention of PCOS. The mechanisms of "inheritance" of PCOS and insulin resistance with the participation of epigenetic modifications are still better understood, taking into account the effects of exposure to androgen excess in utero, intrauterine growth retardation, and maternal obesity and hyperalimentation. This creates new possibilities for PCOS prophylaxis.
References
Abbott, D.H., Kraynak, M., Dumesic, D.A., Levine, J.E. (2019). In utero Androgen Excess: A Developmental Commonality Preceding Polycystic Ovary Syndrome? Frontiers of Hormone Research, 53, 1–17, https://doi.org/10.1159/000494899.
Arentz, S., Smith, C.A., Abbott, J., Bensoussan, A. (2021). Perceptions and experiences of lifestyle interventions in women with polycystic ovary syndrome (PCOS), as a management strategy for symptoms of PCOS, BMC Womens. Health, 21, 1–8, https://doi.org/10.1186/s12905-021-01252-1.
Azizi Kutenaei, M., Hosseini Teshnizi, S., Ghaemmaghami, P., Eini, F., Roozbeh, N. (2021). The effects of myo-inositol vs. metformin on the ovarian function in the polycystic ovary syndrome: A systematic review and meta-analysis, European Reviev for Medical and Pharmacological Sciences, 25, 3105–3115, https://doi.org/10.26355/eurrev_202104_25565.
Azziz, R., Carmina, E., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H.F., Futterweit, W., Janssen, O.E., Legro, R.S., Norman, R.J., Taylor, A.E., Witchel, S.F. (2009). The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report, Fertility and Sterility, https://doi.org/10.1016/j.fertnstert.2008.06.035.
Barker, D.J.P. (2002). Fetal programming of coronary heart disease, Trends in Endocrinology & Metabolism, 13, 364–368, https://doi.org/10.1016/s1043-2760(02)00689-6.
Bozdag, G., Mumusoglu, S., Zengin, D., Karabulut, E., Yildiz, B.O. (2016). The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis, Human Reproduction, 31, 2841–2855, https://doi.org/10.1093/humrep/dew218.
Calcaterra, V., Cena, H., Regalbuto, C., Vinci, F., Porri, D., Verduci, E., Chiara, M., Zuccotti, G.V. (2021a). The role of fetal, infant, and childhood nutrition in the timing of sexual maturation, Nutrients, 13, 419, https://doi.org/10.3390/nu13020419.
Calcaterra, V., Verduci, E., Cena, H., Magenes, V.C., Todisco, C.F., Tenuta, E., Gregorio, C., De Giuseppe, R., Bosetti, A., Di Profio, E., Zuccotti, G. (2021b). Polycystic ovary syndrome in insulin- resistant adolescents with obesity: The role of nutrition therapy and food supplements as a strategy to protect fertility, Nutrients, 13, 1848, https://doi.org/10.3390/nu13061848.
Christensen, S.B., Black, M.H., Smith, N., Martinez, M.M., Jacobsen, S.J., Porter, A.H., Koebnick, C. (2013). Prevalence of polycystic ovary syndrome in adolescents, Fertility and Sterility, 100, 470–477, https://doi.org/10.1016/j.fertnstert.2013.04.001.
Cwynar-Zając, Ł. (2021). Metformin – a new approach. Pediatric Endocrinology Diabetes and Metabolism, 27 (2), 134-140, https://doi.org/10.5114/pedm.2021.107166.
Conway, G., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H.F., Franks, S., Gambineri, A., Kelestimur, F., Macut, D., Micic, D., Pasquali, R., Pfeifer, M., Pignatelli, D., Pugeat, M., Yildiz, B.O. (2014). The polycystic ovary syndrome: A position statement from the European Society of Endocrinology, European Journal of Endocrinology, 171, 1–29, https://doi.org/10.1530/EJE-14-0253.
De Diego, M.V., Gómez-Pardo, O., Groar, J.K., López-Escobar, A., Martín-Estal, I., Castilla- Cortázar, I., Rodríguez-Zambrano, M.Á. (2020). Metabolic impact of current therapeutic strategies in Polycystic Ovary Syndrome: a preliminary study, Archives of Gynecology and Obstetrics, 302, 1169–1179, https://doi.org/10.1007/s00404-020-05696-y.
Díaz, M., Bassols, J., López-Bermejo, A., De Zegher, F., Ibáñez, L. (2020). Low Circulating Levels of miR-451a in Girls with Polycystic Ovary Syndrome: Different Effects of Randomized Treatments, Journal of Clinical Endocrinology and Metabolism, 105, 273–281, https://doi.org/10.1210/clinem/dgz204.
Drosdzol-Cop, A., Tymińska-Bandoła, A., Bil, A., Stojko, R., Skrzypulec-Plinta, V. (2017). Zespół policystycznych jajników u nastolatek – diagnostyka i leczenie, Ginekologia po Dyplomie, https://podyplomie.pl/ginekologia/26793,zespol-policystycznych-jajnikow-u-nastolatek-diagnostyka-i-leczenie.
Elenis, E., Desroziers, E., Persson, S., Sundström Poromaa, I., Campbell, R.E. (2021). Early initiation of anti-androgen treatment is associated with increased probability of spontaneous conception leading to childbirth in women with polycystic ovary syndrome: a population-based multiregistry cohort study in Sweden, Human Reproduction, 36, 1427–1435, https://doi.org/10.1093/humrep/deaa357.
Fauser, B.C.J.M. (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome, Fertility and Sterility, 81, 19–25, https://doi.org/10.1016/j.fertnstert.2003.10.004.
Gołąbek, K.D., Regulska-Ilow, B. (2019). Dietary support in insulin resistance: An overview of current scientific reports, Advances in Clinical and Experimental Medicine, 28, 1577- 1585, https://doi.org/10.17219/ACEM/109976.
Goyal, D., Limesand, S.W., Goyal, R. (2019). Epigenetic responses and the developmental origins of health and disease, Journal of Endocrinology, 242, T105–T119, https://doi.org/10.1530/JOE-19-0009.
Hecht Baldauff, N., Arslanian, S. (2015). Optimal management of polycystic ovary syndrome in adolescence, Archives of Disease in Childhood, 100, 1076–1083, https://doi.org/10.1136/archdischild-2014-306471.
Hiam, D., Moreno-Asso, A., Teede, H.J., Laven, J.S.E., Stepto, N.K., Moran, L.J., Gibson- Helm, M. (2019). The Genetics of Polycystic Ovary Syndrome: An Overview of Candidate Gene Systematic Reviews and Genome-Wide Association Studies, Journal of Clinical Medicine, 8, 1606, https://doi.org/10.3390/jcm8101606.
Hickey, M., Doherty, D.A., Atkinson, H., Sloboda, D.M., Franks, S., Norman, R.J., Hart, R. (2011). Clinical, ultrasound and biochemical features of polycystic ovary syndrome in adolescents: Implications for diagnosis, Human Reproduction, 26, 1469–1477, https://doi.org/10.1093/humrep/der102.
Hilgers, T. (2004). Medical Treatment of Ovarian and Target Organ Dysfunction (in:) Hilgers T. (ed.) The Medical & Surgical Practice of NaProTECHNOLOGY, 607-633, Pope Paul VI Institute Press, Omaha, Nebraska, USA.
Hoeger, K.M. (2007). Obesity and lifestyle management in polycystic ovary syndrome, Clinical Obstetrics and Gynecology, 50, 277–294, https://doi.org/10.1097/GRF.0b013e31802f54c8.
Ibáñez, L., Díaz, M., García-Beltrán, C., Malpique, R., Garde, E., López-Bermejo, A., de Zegher, F. (2020). Toward a Treatment Normalizing Ovulation Rate in Adolescent Girls With Polycystic Ovary Syndrome, Journal of the Endocrine Society, 4, 1-9, https://doi.org/10.1210/jendso/bvaa032.
Ibáñez, L., Oberfield, S.E., Witchel, S., Auchus, R.J., Chang, R.J., Codner, E., Dabadghao, P., Darendeliler, F., Elbarbary, N.S., Gambineri, A., Garcia Rudaz, C., Hoeger, K.M., López-Bermejo, A., Ong, K., Peña, A.S., Reinehr, T., Santoro, N., Tena-Sempere, M., Tao, R., Yildiz, B.O., Alkhayyat, H., Deeb, A., Joel, Di., Horikawa, R., De Zegher, F., Lee, P.A. (2017). An International Consortium Update: Pathophysiology, Diagnosis and Treatment of Polycystic Ovarian Syndrome in Adolescence, Hormone Research in Paediatrics, 88, 371–395, https://doi.org/10.1159/000479371.
Khashchenko, E., Uvarova, E., Vysokikh, M., Ivanets, T., Krechetova, L., Tarasova, N., Sukhanova, I., Mamedova, F., Borovikov, P., Balashov, I., Sukhikh, G. (2020). The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents, Journal of Clinical Medicine, 9, 1831, https://doi.org/10.3390/jcm9061831.
Lewandowski, K.C., Cajdler-Łuba, A., Salata, I., Bieńkiewicz, M., Lewiński, A. (2011). The utility of the gonadotrophin releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS), Endokrynologia Polska, 62, 120–128.
Ma, R., Ding, X., Wang, Y., Deng, Y., Sun, A. (2021). The therapeutic effects of glucagon-like peptide-1 receptor agonists and metformin on polycystic ovary syndrome, Medicine (Baltimore), 100, e26295, https://doi.org/10.1097/md.0000000000026295.
Milczarek, M., Kucharska, A., Borowiec, A. (2019). Difficulties in diagnostics of polycystic ovary syndrome in adolescents – a preliminary study, Pediatric Endocrinology, Diabetes and Metabolism, 25 (3), 122-126, https://doi.org/10.5114/pedm.2019.87177.
Milewicz, A., Kudła, M., Spaczyński, R.Z., Dębski, R., Męczekalski, B., Wielgoś, M., Ruchała, M., Małecka-Tendera, E., Kos-Kudła, B., Jędrzejuk, D., Zachurzok, A. (2018). Stanowisko Polskiego Towarzystwa Endokrynologicznego, Polskiego Towarzystwa Ginekologów i Położników oraz Polskiego Towarzystwa Endokrynologii Ginekologicznej w sprawie diagnostyki i leczenia zespołu policystycznych jajników, Endokrynologia Polska, 69, 328–336, https://doi.org/10.5603/ep.2018.0046.
Nokoff, N., Thurston, J., Hilkin, A., Pyle, L., Zeitler, P.S., Nadeau, K.J., Santoro, N., Kelsey, M.M. (2019). Sex Differences in Effects of Obesity on Reproductive Hormones and Glucose Metabolism in Early Puberty, Journal of Clinical Endocrinology and Metabolism, 104, 4390–4397, https://doi.org/10.1210/jc.2018-02747.
Oberfield, S.E., Sopher, A.B., Gerken, A.T. (2011). Approach to the girl with early onset of pubic hair, Journal of Clinical Endocrinology and Metabolism, 96, 1610–1622, https://doi.org/10.1210/jc.2011-0225.
Otto-Buczkowska, E., Grzyb, K., Jainta, N. (2018). Polycystic ovary syndrome (PCOS) and the accompanying disorders of glucose homeostasis among girls at the time of puberty, Pediatric Endocrinology Diabetes and Metabolism, 24 (1), 38-42, https://doi.org/10.18544/PEDM-24.01.0101.
Pasquali, R. (2006). Obesity and androgens: facts and perspectives, Fertility and Sterility, 85, 1319–1340, https://doi.org/10.1016/j.fertnstert.2005.10.054.
Peña, A.S., Witchel, S.F., Hoeger, K.M., Oberfield, S.E., Vogiatzi, M.G., Misso, M., Garad, R., Dabadghao, P., Teede, H. (2020). Adolescent polycystic ovary syndrome according to the international evidence-based guideline, BMC Medicine, 18, 72, https://doi.org/10.1186/s12916-020-01516-x.
Reinehr, T., de Sousa, G., Roth, C.L., Andler, W. (2005). Androgens before and after weight loss in obese children, Journal of Clinical Endocrinology and Metabolism, 90, 5588–5595, https://doi.org/10.1210/jc.2005-0438.
Şanlı, E., Kabaran, S. (2019). Maternal Obesity, Maternal Overnutrition and Fetal Programming: Effects of Epigenetic Mechanisms on the Development of Metabolic Disorders, Current Genomics, 20, 419–427, https://doi.org/10.2174/1389202920666191030092225.
Stein, I.F., Leventhal, M.L. (1935). Amenorrhoea associated with bilateral polycystic ovaries, American Journal of Obstetrics and Gynecology, 29, 181-191.
Tsiami, A.P., Goulis, D.G., Sotiriadis, A.I., Kolibianakis, E.M. (2021). Higher ovulation rate with letrozole as compared with clomiphene citrate in infertile women with polycystic ovary syndrome: a systematic review and meta-analysis, Hormones, https://doi.org/10.1007/s42000-021-00289-z.
Urbańska, E., Hirnle, L., Olszanecka-Glinianowicz, M., Skrzypulec-Plinta, V., Skrzypulec- Frankel, A., Drosdzol-Cop. A (2019). Is polycystic ovarian syndrome and insulin resistance associated with abnormal uterine bleeding in adolescents? Ginekologia Polska, 90, 262-269, https://doi.org/10.5603/GP.2019.0049.
Vaiserman, A., Lushchak, O. (2019). Prenatal malnutrition-induced epigenetic dysregulation as a risk factor for type 2 diabetes, International Journal of Genomics, https://doi.org/10.1155/2019/3821409.
Wang, L., Lv, S., Li, F., Bai, E., Yang, X. (2021). Letrozole Versus Clomiphene Citrate and Natural Cycle: Endometrial Receptivity During Implantation Window in Women With Polycystic Ovary Syndrome, Frontiers in Endocrinology (Lausanne), 11, https://doi.org/10.3389/fendo.2020.532692.
Witchel, S.F., Oberfield, S., Rosenfield, R.L., Codner, E., Bonny, A., Ibáñez, L., Pena, A., Horikawa, R., Gomez-Lobo, V., Joel, D., Tfayli, H., Arslanian, S., Dabadghao, P., Garcia Rudaz, C., Lee, P.A. (2015). The Diagnosis of Polycystic Ovary Syndrome during Adolescence, Hormone Research in Paediatrics, 83, 376–389, https://doi.org/10.1159/000375530.
Zhou, Y., Gu, P., Shi, W., Li, J., Hao, Q., Cao, X., Lu, Q., Zeng, Y. (2016). MicroRNA-29a induces insulin resistance by targeting PPARδ in skeletal muscle cells, International Journal of Molecular Medicine, 37, 931–938, https://doi.org/10.3892/ijmm.2016.2499.