The importance of melatonin in ovarian syndrome polycystic: A bibliographic review




Melatonin; Polycystic ovary syndrome; Sleep; Sleep disorders; Health teaching.


Introduction: Polycystic Ovary Syndrome (PCOS) is characterized by a multiple and complex endocrine disorder that leads to hyperandrogenism, menstrual irregularity and can lead to infertility. In this review, we will present an overview of PCOS, by summarizing the clinical and epidemiological literature related to the disorders of this syndrome, and associating it with melatonin. Methodology: This is a descriptive qualitative study, called an integrative literature review, it is a relevant instrument in the communication of research results, facilitating the use of these results in clinical practice, as it provides a synthesis of the knowledge already produced and provides contributions to the improvement of health care, through research in scientific articles present in databases. traditional medical knowledge data: PUBMED/MedLine, Scopus, Embase, Cochranne. Results: Polycystic ovary syndrome affects thousands of women worldwide, being a very complex disorder of multiple endocrine order, linked to hyperandrogenism and menstrual disorder, which can cause a series of complications that lead to infertility. women who want to reproduce. Discovering ways of reversing and recovering the characteristics of female reproduction would reduce the anguish of millions of women in the world. Conclusion: Despite the positive influence of melatonin on reproductive function, we did not observe in the literature randomized controlled studies comparing its use in women with PCOS More studies should be undertaken in this regard. There is no consistent evidence for the systematic use of melatonin in women with PCOS or chronic anovulatory women.

Author Biographies

Mariana Goes da Souza Silva, Universidade Federal do Tocantins

Acadêmico de Medicina

Lívia Benvindo do Carmo, Universidade Federal do Tocantins

Acadêmica de Medicina

Márcia Cristina Terra de Siqueira Peres, Universidade Federal do Tocantins

Professora Adjunto da ITPAC Palmas desde fevereiro 2019 e Professora da Universidade Federal do Tocantins desde março de 2014. Graduada em Medicina pela Universidade Federal de Uberlândia (1989), especialização em Ginecologia e Obstetrícia pela Universidade Federal de Uberlândia(1991) e Título de Especialista em Ginecologia e Obstetrícia (2008) . Concluiu Mestrado em Psicologia pela Universidade Federal de Uberlândia (2005). Possui Área de Atuação em Sexologia. Atualmente atua como médica ginecologista, terapeuta sexual e na área de auditoria e perícia médica. Tem experiência na área de Ginecologia Obstetrícia, Psicanálise, Sexologia. Concluiu Pós Graduação na área de Perícia Médica. Sua produção acadêmica envolve os seguintes temas: método psicanalítico, relação médico-paciente, função terapêutica, teoria dos campos, sexologia, climatério e endocrinologia ginecológica.


Ahmadieh, E. S. A. (2017). Efeitos do cotrano de glicose de sódio inibidores do esporter-2 no ácido úrico sérico em diabetes mellitus tipo 2, Diabetes Technology & Therapeutics. 19(9), 507-12.

Amstrup, T., Sikjaer, S. B., Pedersin, L., Heickendor, F. F., Mosekilde, E. & Rejnmark, L. (2016). Redução da massa gorda e aumento da massa magra em resposta a 1 ano de tratamento com melatonina em mulheres pós-menopáusicas: um ensaio randomizado controlado com placebo. Endocrinologia Clínica. 84(3), 342-7.

Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J Clin Endocrinol Metab 91:781–5.

Azziz R, Black V. Y, Knochenhauer E. S, Hines G. A, & Boots L. R. Ovulation after glucocorticoid suppression of adrenal androgens in the polycystic ovary syndrome is not pre- dicted by the basal dehydroepiandrosterone sulfate level. J Clin Endocrinol Metab 1999; 84: 946–950.

Barber T. M, & Franks S. Adipocyte biology in polycystic ovary syndrome. Mol Cell Endocrinol. 2013; 373: 68-76.

Basheer M, & Rai S. Melatonin vs. phytomelatonin: Thera- peutic uses with special reference to polycystic ovarian syndrome (PCOS). Cogent Biol 2016; 2: 1136257.

Borjigin, J., Zhang, L. S., & Calinescu, A. A. (2012). Circadian regulation of pineal gland rhythmicity. Molecular and Cellular Endocrinology, 349, 13–19.

Comhair, S. A. A.; & Erzurum, S. C. Antioxidant responses to oxidant-mediated lung diseases. American Journal of Physiology - Lung Cellular and Molecular Physiology, 283, L246-L255. 10.1152/ajplung.00491.2001.

Dubocovich, M. L. (2007). Melatonin receptors: Role on sleep and circadian rhythm reg- ulation. Sleep Medicine, 8(Suppl. 3), 34–42.

Dubocovich, M. L., Delagrange, P., Krause, D. N., Sugden, D., Cardinali, D. P. &Olcese, J. (2010) International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol. Rev. 62, 343–380,

Eckel, R. H. C.M Depner, L. Perreault et al. (2015). “Manhã o desalinhamento circadiano durante a curta duração do sono afeta a sensibilidade à insulina, ” Biologia Atual, 25(22), 3004 – 3010

Erickson G. F, & Shimasaki S. (2003)The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod Biol Endocrinol, 1, 9

Fernandez, R. C. et al. (2018) Sleepdisturbances in womenwithpolycysticovarysyndrome: prevalence, pathophysiology, impactand management strategies. Natureand Science ofSleep, 10, 45–64.

González F, Rote N. S, Minium J, Kirwan J. P. Reactive oxy- gen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab. 91:336– 340.

Goodman, N. F., Cobin, R. H., Futterweit, W. et al. (2015) American association of clinical endocrinologists, American college of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome–part 1. Endocr. Pract. 21, 1291–1300.

Gupta R. K, Miller K. P, Babus J. K, & Flaws J A. Methoxychlor inhibits growth and induces atresia of antral follicles through an oxidative stress pathway. Toxicol Sci 2006; 93: 382–389.

Halliwell, B.; & Gutteridge, J. M. C. Lipid peroxidation: a radical chain reaction. In: Halliwell, B.; & Gutteridge, J. M. C. Free radical in biology an medicine. New York: Oxford University, 1999. 189- 276.

Hazlerigg, D. G., Morgan, P. J., & Messager, S. (2001). Decoding photoperiodic time and melatonin in mammals: What can we learn from the pars tuberalis? Journal of Biological Rhythms, 16, 326–335

Johansson J, & Stener-Victorin E. (2013) Polycystic ovary syn- drome: effect and mechanisms of acupuncture for ovu- lation induction. Evid Based Complement Alternat Med 762615.

Lee Y. H, & Pratley R. E. (2005) The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep. 5:70-75.

Lew, K. N. E. A. Wick, (2015). “Farmacoterapia de diabetes tipo 2 mellitus: navegando nas terapias atuais e novas, ” Enfermagem Medsurg, 24, 413 – 419

Lim, R. Z. Huang, S. E Chua, M S Kramer & EL Yong, “Resultados relacionados à duração do sono, exercícios, turnos de trabalho e síndrome do ovário policístico em uma população saudável: um estudo transversal, ” PLoS One, 11(11), artigo e0167048, 2016.

Luboshitzky, R., Qupti, G., Ishay, A., Shen-Orr, Z., Futerman, B. & Linn, S. (2001) Increased 6-sulfatoxymelatonin excretion in women with polycystic ovary syndrome. Fertil. Steril. 76, 506–510.

Kinnula, V. L. et al. Generation and disposal of reactive oxygen metabolites in the lung. Laboratory Investagation, 73(1), 3-19, 1995.

Kwak-Kim J, Bao S, Lee S. K, Kim J. W, & Gilman-Sachs A. Immunological modes of pregnancy loss: inflammation, immune effectors, and stress. Am J Reprod Immunol. 2014; 72:129-140.

Kahal, I. Kyrou, A. A. Tahrani, AND H. S. Randeva, “Obstructive sleep apnoea and polycystic ovary syndrome: a comprehensive review of clinical interactions and underlying pathophysiology,” Clinical Endocrinology, 87(4), 313–319, 2017.

Kun Y. U et al. MelatoninReducesAndrogenProductionandUpregulates Heme Oxygenase-1 Expression in Granulosa Cellsfrom PCOS PatientswithHypoestrogeniaandHyperandrogenia. HindawiOxidative Medicine andCellularLongevity, 2019. Acesso em: 09 de junho 2021.

Majumdar A, Sharma M. N. Anovulatory Infertility. I. N: Kamini AR. Principles & Practice of Assisted Reproductive Tech- nology. New Delhi, India: Jaypee Brothers Medical Pub-lishers LTD., 2014.

March W. A, Moore V M, Willson K. J, Phillips D. I, Norman R. J, Davies M. J. The pre-valence of polycystic ovary syndrome in a community sample assessed under con- trasting diagnostic criteria. Hum Reprod (Oxf Engl) 2010;25:544–51

Mesri Alamdari, R. Mahdavi, N. Roshanravan, N. Lotfi Yaghin, A. Ostadrahimi, and E. Faramarzi, “A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women,” Hormone and Metabolic Research, 47(7), 504–508, 2015.

Mccartney, “Maturation of sleep–wake gonadotrophin- releasing hormone secretion across puberty in girls: potential mechanisms and relevance to the pathogenesis of polycystic ovary syndrome,” Journal of Neuroendocrinology, 22(7), 701–709, 2010.

Mccartney C. R, Eagleson C A, & Marshall J C. Regulation of gonadotropin secretion: implications for polycystic ovarysyndrome. Seminars in reproductive medicine. Semin Reprod Med 2002; 20: 317–326.

Mojaver Rostami, S. et al. The role ofmelatonin in polycysticovarysyndrome: A review.InternationalJournalofReproductiveBioMedicine, 17, edição nº 12, 2019. Acesso em: 30 maio 2021.

Moran, W. A. March, M. J. Whitrow, L. C. Giles, M. J. Davies, and V. M. Moore, “Sleep disturbances in a community-based sample of women with polycystic ovary syndrome,” Human Reproduction, 30(2), 466– 472, 2015.

Mokhtari, F., Akbari Asbagh, F., Azmoodeh, O., Bakhtiyari, M. And Almasi-Hashiani, A. (2019) Effects of melatonin administration on chemical pregnancy rates of polycystic ovary syndrome patients undergoing intrauterine insemination: a randomized clinical trial. Int. J. Fertil. Steril. 13, 225–229.

Nakamura, E., Otsuka, F., Terasaka, T., Inagaki, K., Hosoya, T., Tsukamoto-Yamauchi, N. et al. (2014). Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granu-losa cells. The Journal of Steroid Biochemistry and Molecular Biology, 143, 233–239.

Ostrowska Z, Kos-Kudla B, Nowak M, Swietochowska E, Marek B, Gorski J, et al. The relationship between bone metabolism, melatonin and other hormones in sham-operated and pinealectomized rats. Endocr Regul. 2003,37(4):211-24.

Otzuca.F.(2018). Interaction of Melatonin and BMP-6 in Ovarian Steroidogenesis.Vitamins qnd Hormones.vol.107.

Polak K, Czyzyk A, Simoncini T, Meczekalski B. New markers of insulin resistance in polycystic ovary syndrome. J Endocrinol Invest 2017; 40: 1–8.

Reiter, R. J., Tamura, H., Tan, D. X., & Xu, X. Y. (2014). Melatonin and the circadian system: Contributions to successful female reproduction. Fertility and Sterility, 102, 321–328.

Reiter, R. J., Rosales-Corral, S. A., Manchester, L. C., & Tan, D. X. (2013). Peripheral reproductive organ health and melatonin: Ready for prime time. International Journal of Molecular Sciences, 14, 7231–7272.

Ridker P. M, Buring J. E, Cook N. R, & Rifai N. C-reactive protein, the metabolic syn- drome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719initially healthy American women. Circulation 2003; 107:391–7.

Reiter R. J, Tan D. X. & Galano A. Melatonin: exceeding expectations. Physiology. 2014; 29:325-333.

ROTTERDAM ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, “Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome,” Fertility and Sterility, 81(1), 19–25, 2004.

Rubin, K. H. K. D. Glintborg, M. & Nybo, B. Abrahamsen, an M. Andersen, “Development and risk factors of type 2 diabetes in a nationwide population of women with poly- cystic ovary syndrome,” The Journal of Clinical Endocri- nology and Metabolism, vol. 102, no. 10, pp. 3848–3857, 2017.

Santos, R. M; & Álvares, A. C. Revisão de literatura sobre a síndrome do ovário policístico. RevInicCienteExt.1(Esp.2):261-5,2018.

Saha, L., Kaur, S., & Saha, P. K. (2012). Pharmacotherapy of polycystic ovary syndrome—Anupdate. Fundamental & Clinical Pharmacology, 26, 54–62.

Shabani, A., Foroozanfard, F., & Kavossian, E. et al. (2019) Effects of melatonin administration on mental health parameters, metabolic and genetic profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. J. Affect. Disord. 250, 51–56,

Speroff L, Fritz Ma Obesity. The physiology of adipose tissue, and the problem of obesity. In: Speroff L, Fritz MA, editors. Clinical gynecologic endocrinology and infertility. Philadelphia: Lippincott Williams & Wilkins; 2005. 779-804.

Spinedi.E. Daniel P. Cardinali. The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy.Hindawi. International Journal of Endocrinology. 2018.

Spinedi, V. Mariani, M. Bulfon, M. Colombani-Vidal, & H. Scaglia, “Analysis of the hypothalamic-pituitary-ovary axis in the neonatally-androgenized female rat,” Journal of Endocrinological Investigation, 13(6), 481–488, 1990.

Stanosz, J. Von Mach-Szczypinski, K. Sieja, And J. Kooeciuszkiewicz, “Micronized estradiol and progesterone therapy in primary, preinvasive endometrial cancer (1A/G1) in young women with polycystic ovarian syndrome,” The Journal of Clinical Endocrinology and Metabolism, 99(12), E2472–E2476, 2014.

Tamura, H., Takasaki, A., Taketani, T., Tanabe, M., Kizuka, F., Lee, L., et al. (2013). mel- atonin as a free radical scavenger in the ovarian follicle. Endocrine Journal, 60, 1–13.

Tamura H, Nakamura Y, Korkmaz A, Manchester Lc, Tan Dx, Sugino N, et al. Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 2009; 92:328–343.

Tarquini, R., Bruni, V., Perfetto, F., Bigozzi, L., Tapparini, L. And Tarquini, B. (1996) Hypermelatoninemia in women with polycystic ovarian syndrome. Eur. J. Contracept. Reprod. Health Care 1, 349–350

THE ROTTERDAM ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19(1):41-7.

Van Houten, E. L., Laven, J. S., Louwers, Y. V., Mcluskey, A., Themmen, A. P., & Visser, J. A. (2013). Bone morphogenetic proteins and the polycystic ovary syndrome. Journal of Ovarian Research, 6, 32.

Valko M. et al. Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry & Cell Biology, 39, 44-84, 2007.

Voznesenskaya T, Makogon N, Bryzgina T, Sukhina V, Grushka, N, Alexeyeva I. Melatonin protects against experimental immune ovarian failure in mice. Reprod Biol. 2007; 7:207-220.

Zhang T., Tian F., Huo R., Tang, A., Zeng Y., Duan Y. G. Detection of den- dritic cells and related cytokines in follicular fluid of patients with polycystic ovary syndrome. Am J Reprod Immunol. 2017; 78:e12717.

Wild S, Pierpoint T, Mckeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 2000; 52:595–600.

Woo, M. M., Tai, C. J., Kang, S. K., Nathwani, P. S., Pang, S. F. & Leung, P. C. (2001) Direct action of melatonin in human granulosa-luteal cells. J. Clin. Endocrinol. Metab. 86, 4789–4797,

Winck, D. R.; & Brüggemann, O. M. Responsabilidade legal do enfermeiro em obstetrícia. Revista Brasileira de Enfermagem. Brasília, 63(3), 464-469, 2010.

Yoshino O, Shi J, Osuga Y, Harada M, Nishii O, Yano T, & Taketani Y. The function of bone morphogenetic proteins in the human ovary. Reprod Med Biol, 10, 1-7, 2011.



How to Cite

NASCIMENTO, R. P. do .; SILVA, M. G. da S. .; CARMO, L. B. do .; PERES, M. C. T. de S. . The importance of melatonin in ovarian syndrome polycystic: A bibliographic review. Research, Society and Development, [S. l.], v. 11, n. 6, p. e0911628483, 2022. DOI: 10.33448/rsd-v11i6.28483. Disponível em: Acesso em: 14 jun. 2024.



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