PSYCHONEUROENDOCRINE ASPECTS OF POLYCYSTIC OVARY SYNDROME: FROM MECHANISMS TO CLINICAL CONSEQUENCES - A COMPREHENSIVE LITERATURE REVIEW
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.4798Keywords:
Polycystic Ovary Syndrome (PCOS), Psychoneuroendocrinology, Hyperandrogenism, Insulin Resistance, Mental Health Disorders, InflammationAbstract
Purpose: Growing evidence conceptualizes Polycystic Ovary Syndrome (PCOS) as a complex psychoneuroendocrine condition whose consequences extend far beyond reproductive health. Research indicates that hyperandrogenism, insulin resistance, and chronic low-grade inflammation interact dynamically, affecting central nervous system functioning, stress responsiveness, and neurotransmitter regulation. These interrelated mechanisms contribute to a substantially increased vulnerability to depression, anxiety, disordered eating behaviors, and cognitive disturbances in women with PCOS. Dysregulation of both the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-adrenal (HPA) axes, together with adipokine imbalance and neuroinflammatory activity, provides a biologically coherent framework for understanding the heightened psychiatric burden associated with the syndrome.
Importantly, psychological manifestations of PCOS are heterogeneous. Symptom severity and presentation are influenced by phenotype, metabolic status, body composition, age, and exposure to psychosocial and environmental stressors. Interventions targeting metabolic and inflammatory dysfunction, including insulin-sensitizing agents, anti-inflammatory strategies, lifestyle modification, and psychologically informed therapies have shown beneficial effects on mental health and quality of life, though responses vary considerably. These observations highlight the need for individualized, integrative treatment approaches and underscore the importance of longitudinal, mechanism-driven research to improve clinical outcomes.
Methodology: A systematic review of the scientific literature was conducted, focusing on studies examining the psychoneuroendocrine mechanisms and mental health outcomes associated with Polycystic Ovary Syndrome (PCOS). The review primarily included clinical trials, observational studies, meta-analyses, and mechanistic research in human populations, with particular emphasis on endocrine, metabolic, neurobiological, and psychological outcomes.
Findings: PCOS is consistently associated with a significantly increased burden of depression, anxiety, disordered eating, and cognitive complaints, mediated by interconnected psychoneuroendocrine mechanisms. The reviewed evidence indicates that hyperandrogenism, insulin resistance, and chronic low-grade inflammation disrupt neurotransmitter systems, stress-axis regulation, and brain connectivity, collectively contributing to mood dysregulation and reward-processing deficits. Interventions that improve metabolic function such as insulin sensitizers, anti-inflammatory strategies, and lifestyle modification, appear to alleviate psychological symptoms and improve quality of life, although effects vary by PCOS phenotype, metabolic status, age and treatment modality.
Conclusions: Current evidence supports the role of Polycystic Ovary Syndrome as a condition with significant psychoneuroendocrine involvement, contributing to an increased risk of mood disorders, disordered eating, and cognitive dysfunction. However, further high-quality, longitudinal and mechanistically focused studies are required to elucidate the precise causal pathways linking endocrine and metabolic disturbances to brain function, and to determine optimal, personalized management strategies targeting both metabolic and mental health outcomes. These remain critical priorities for future research.
References
Teede, H. J., Tay, C. T., Laven, J. J. E., Dokras, A., Moran, L. J., Piltonen, T. T., Costello, M. F., Boivin, J., Redman, L. M., Boyle, J. A., Norman, R. J., Mousa, A., & Joham, A. E. (2023). Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Journal of Clinical Endocrinology & Metabolism, 108(10), 2447–2469. https://doi.org/10.1210/clinem/dgad463
Lizneva, D., Suturina, L., Walker, W., Brakta, S., Gavrilova-Jordan, L., & Azziz, R. (2016). Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertility and Sterility, 106(1), 6–15. https://doi.org/10.1016/j.fertnstert.2016.05.003
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(12), 2841–2855. https://doi.org/10.1093/humrep/dew218
Risal, S., Pei, Y., Lu, H., Manti, M., Fornes, R., Pui, H. P., Zhao, Z., Massart, J., Ohlsson, C., Lindgren, E., Crisosto, N., Maliqueo, M., Echiburú, B., Ladrón de Guevara, A., Sir-Petermann, T., Larsson, H., Rosenqvist, M. A., Cesta, C. E., Benrick, A., Deng, Q., & Stener-Victorin, E. (2019). Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nature Medicine, 25(12), 1894–1904. https://doi.org/10.1038/s41591-019-0666-1
Rosenfield, R. L. (2007). Clinical review: Identifying children at risk for polycystic ovary syndrome. Journal of Clinical Endocrinology & Metabolism, 92(3), 787–796. https://doi.org/10.1210/jc.2006-2012
Amiri, M., Hatoum, S., Buyalos, R. P., Sheidaei, A., & Azziz, R. (2025). The influence of study quality, age, and geographic factors on PCOS prevalence—A systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism, 110(7), 2082–2103. https://doi.org/10.1210/clinem/dgae917
Wolf, W. M., Wattick, R. A., Kinkade, O. N., & Olfert, M. D. (2018). Geographical prevalence of polycystic ovary syndrome as determined by region and race/ethnicity. International Journal of Environmental Research and Public Health, 15(11), 2589. https://doi.org/10.3390/ijerph15112589
Krentowska, A., & Kowalska, I. (2022). Metabolic syndrome and its components in different phenotypes of polycystic ovary syndrome. Diabetes/Metabolism Research and Reviews, 38(1), e3464. https://doi.org/10.1002/dmrr.3464
Dapas, M., Lin, F. T. J., Nadkarni, G. N., Sisk, R., Legro, R. S., Urbanek, M., Hayes, M. G., & Dunaif, A. (2020). Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. PLOS Medicine, 17(6), e1003132. https://doi.org/10.1371/journal.pmed.1003132
Sachdeva, G., Gainder, S., Suri, V., Sachdeva, N., & Chopra, S. (2019). Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to clomiphene. Indian Journal of Endocrinology and Metabolism, 23(3), 326–331. https://doi.org/10.4103/ijem.IJEM_30_19
Cooney, L. G., Lee, I., Sammel, M. D., & Dokras, A. (2017). High prevalence of moderate and severe depressive and anxiety symptoms in polycystic ovary syndrome: A systematic review and meta-analysis. Human Reproduction, 32(5), 1075–1091. https://doi.org/10.1093/humrep/dex044
Brutocao, C., Zaiem, F., Alsawas, M., Morrow, A. S., Murad, M. H., & Javed, A. (2018). Psychiatric disorders in women with polycystic ovary syndrome: A systematic review and meta-analysis. Endocrine, 62(2), 318–325. https://doi.org/10.1007/s12020-018-1692-3
Krug, I., Giles, S., & Paganini, C. (2019). Binge eating in patients with polycystic ovary syndrome: Prevalence, causes, and management strategies. Neuropsychiatric Disease and Treatment, 15, 1273–1285. https://doi.org/10.2147/NDT.S168944
Durdiakova, J., Ostatnikova, D., & Celec, P. (2011). Testosterone and its metabolites—Modulators of brain functions. Acta Neurobiologiae Experimentalis, 71(4), 434–454. https://doi.org/10.55782/ane-2011-1863
Ramezanpour, M., Bahrami, O., Pashazadeh, M., Sarallah, R., Nikfar, R., & Majidi Zolbin, M. (2025). Polycystic ovary syndrome PCOS and depression role of neuroinflammation. https://doi.org/10.4018/979-8-3693-5908-2.ch007
Benson, S., Arck, P. C., Tan, S., Hahn, S., Mann, K., Rifaie, N., Janssen, O. E., Schedlowski, M., & Elsenbruch, S. (2009). Disturbed stress responses in women with polycystic ovary syndrome. Psychoneuroendocrinology, 34(5), 727–735. https://doi.org/10.1016/j.psyneuen.2008.12.001
Rodriguez Paris, V., & Bertoldo, M. J. (2019). The mechanism of androgen actions in PCOS etiology. Medical Sciences, 7(9), 89. https://doi.org/10.3390/medsci7090089
Motafeghi, F., Amiri, M., Noroozzadeh, M., & Tehrani, F. R. (2025). The impact of GABA and GABAergic pathway in polycystic ovary syndrome: A systematic review. Obstetrics & Gynecology Science, 68(2), 93–108. https://doi.org/10.5468/ogs.24255
Standeven, L. R., Olson, E., Leistikow, N., Payne, J. L., Osborne, L. M., & Hantsoo, L. (2021). Polycystic ovary syndrome, affective symptoms, and neuroactive steroids: A focus on allopregnanolone. Current Psychiatry Reports, 23(6), 36. https://doi.org/10.1007/s11920-021-01244-w
Maguire, J., & Mody, I. (2008). GABA(A)R plasticity during pregnancy: Relevance to postpartum depression. Neuron, 59(2), 207–213. https://doi.org/10.1016/j.neuron.2008.06.019
Ozgen Saydam, B., & Yildiz, B. O. (2021). Polycystic ovary syndrome and brain: An update on structural and functional studies. Journal of Clinical Endocrinology & Metabolism, 106(2), e430–e441. https://doi.org/10.1210/clinem/dgaa843
Li, G., Hu, J., Zhang, S., Fan, W., Wen, L., Wang, G., & Zhang, D. (2020). Changes in resting-state cerebral activity in women with polycystic ovary syndrome: A functional MR imaging study. Frontiers in Endocrinology, 11, 603279. https://doi.org/10.3389/fendo.2020.603279
Marsh, C. A., Berent-Spillson, A., Love, T., Persad, C. C., Pop-Busui, R., Zubieta, J. K., & Smith, Y. R. (2013). Functional neuroimaging of emotional processing in women with polycystic ovary syndrome: A case-control pilot study. Fertility and Sterility, 100(1), 200–207.e1. https://doi.org/10.1016/j.fertnstert.2013.02.054
Szeliga, A., Rudnicka, E., Maciejewska-Jeske, M., Kucharski, M., Kostrzak, A., Hajbos, M., Niwczyk, O., Smolarczyk, R., & Meczekalski, B. (2022). Neuroendocrine determinants of polycystic ovary syndrome. International Journal of Environmental Research and Public Health, 19(5), 3089. https://doi.org/10.3390/ijerph19053089
Mey, M., Bhatta, S., & Casadesus, G. (2021). Luteinizing hormone and the aging brain. Vitamins and Hormones, 115, 89–104. https://doi.org/10.1016/bs.vh.2020.12.005
Xing, L., Xu, J., Wei, Y., Chen, Y., Zhuang, H., Tang, W., Yu, S., Zhang, J., Yin, G., Wang, R., Zhao, R., & Qin, D. (2022). Depression in polycystic ovary syndrome: Focusing on pathogenesis and treatment. Frontiers in Psychiatry, 13, 1001484. https://doi.org/10.3389/fpsyt.2022.1001484
Mergenthaler, P., Lindauer, U., Dienel, G. A., & Meisel, A. (2013). Sugar for the brain: The role of glucose in physiological and pathological brain function. Trends in Neurosciences, 36(10), 587–597. https://doi.org/10.1016/j.tins.2013.07.001
Wang, K., & Li, Y. (2023). Signaling pathways and targeted therapeutic strategies for polycystic ovary syndrome. Frontiers in Endocrinology, 14, 1191759. https://doi.org/10.3389/fendo.2023.1191759
Amin, M., Horst, N., & Gragnoli, C. (2023). Linkage and association of variants in the dopamine receptor 2 gene (DRD2) with polycystic ovary syndrome. Journal of Ovarian Research, 16(1), 158. https://doi.org/10.1186/s13048-023-01205-2
Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Thanos, P. K., Logan, J., Alexoff, D., Ding, Y. S., Wong, C., Ma, Y., & Pradhan, K. (2008). Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors. NeuroImage, 42(4), 1537–1543. https://doi.org/10.1016/j.neuroimage.2008.06.002
Steegers-Theunissen, R. P. M., Wiegel, R. E., Jansen, P. W., Laven, J. S. E., & Sinclair, K. D. (2020). Polycystic ovary syndrome: A brain disorder characterized by eating problems originating during puberty and adolescence. International Journal of Molecular Sciences, 21(21), 8211. https://doi.org/10.3390/ijms21218211
Chen, Y., Cao, P., & Li, J. (2025). A Mendelian randomization study: Genetically predicted dopamine 4-sulfate to dopamine 3-O-sulfate ratio mediates the association between chemokine C-C motif ligand 11 and polycystic ovary syndrome. Medicine, 104(38), e44448. https://doi.org/10.1097/MD.0000000000044448
Clemente-Suárez, V. J., Redondo-Flórez, L., Beltrán-Velasco, A. I., Martín-Rodríguez, A., Martínez-Guardado, I., Navarro-Jiménez, E., Laborde-Cárdenas, C. C., & Tornero-Aguilera, J. F. (2023). The role of adipokines in health and disease. Biomedicines, 11(5), 1290. https://doi.org/10.3390/biomedicines11051290
Fu, X., Wang, Y., Zhao, F., Cui, R., Xie, W., Liu, Q., & Yang, W. (2023). Shared biological mechanisms of depression and obesity: Focus on adipokines and lipokines. Aging, 15(12), 5917–5950. https://doi.org/10.18632/aging.204847
Valladolid-Acebes, I. (2024). Hippocampal leptin resistance and cognitive decline: Mechanisms, therapeutic strategies and clinical implications. Biomedicines, 12(11), 2422. https://doi.org/10.3390/biomedicines12112422
Liao, B., Qiao, J., & Pang, Y. (2021). Central regulation of PCOS: Abnormal neuronal-reproductive-metabolic circuits in PCOS pathophysiology. Frontiers in Endocrinology, 12, 667422. https://doi.org/10.3389/fendo.2021.667422
Zou, X., Zhong, L., Zhu, C., Zhao, H., Zhao, F., Cui, R., Gao, S., & Li, B. (2019). Role of leptin in mood disorder and neurodegenerative disease. Frontiers in Neuroscience, 13, 378. https://doi.org/10.3389/fnins.2019.00378
Li, W., Liu, C., Yang, Q., Zhou, Y., Liu, M., & Shan, H. (2022). Oxidative stress and antioxidant imbalance in ovulation disorder in patients with polycystic ovary syndrome. Frontiers in Nutrition, 9, 1018674. https://doi.org/10.3389/fnut.2022.1018674
Jovanovic, F., Sudhakar, A., & Knezevic, N. N. (2022). The kynurenine pathway and polycystic ovary syndrome: Inflammation as a common denominator. International Journal of Tryptophan Research, 15, 11786469221099214. https://doi.org/10.1177/11786469221099214
Xing, L., Xu, J., Wei, Y., Chen, Y., Zhuang, H., Tang, W., Yu, S., Zhang, J., Yin, G., Wang, R., Zhao, R., & Qin, D. (2022). Depression in polycystic ovary syndrome: Focusing on pathogenesis and treatment. Frontiers in Psychiatry, 13, 1001484. https://doi.org/10.3389/fpsyt.2022.1001484
Sobczuk, J., Paczkowska, K., Andrusiów, S., Bolanowski, M., & Daroszewski, J. (2024). Are women with polycystic ovary syndrome at increased risk of Alzheimer disease? Lessons from insulin resistance, tryptophan and gonadotropin disturbances and their link with amyloid-beta aggregation. Biomolecules, 14(8), 918. https://doi.org/10.3390/biom14080918
Zafari Zangeneh, F., Naghizadeh, M. M., & Masoumi, M. (2017). Polycystic ovary syndrome and circulating inflammatory markers. International Journal of Reproductive BioMedicine, 15(6), 375–382.
Motafeghi, F., Amiri, M., Noroozzadeh, M., & Tehrani, F. R. (2025). The impact of GABA and GABAergic pathway in polycystic ovary syndrome: A systematic review. Obstetrics & Gynecology Science, 68(2), 93–108. https://doi.org/10.5468/ogs.24255
Dybciak, P., Raczkiewicz, D., Humeniuk, E., Powrózek, T., Gujski, M., Małecka-Massalska, T., Wdowiak, A., & Bojar, I. (2023). Depression in polycystic ovary syndrome: A systematic review and meta-analysis. Journal of Clinical Medicine, 12(20), 6446. https://doi.org/10.3390/jcm12206446
Humeniuk, E., Dybciak, P., Raczkiewicz, D., Powrózek, T., Malecka-Massalska, T., Andrzejczyk, A., Suski, K., & Bojar, I. (2025). Anxiety in polycystic ovary syndrome: A meta-analysis. Annals of Agricultural and Environmental Medicine, 32(2), 190–197. https://doi.org/10.26444/aaem/202444
Gül, Ö., Akkuş, M., & Akkuş, F. (2025). Depression, anxiety, and stress in polycystic ovary syndrome: Understanding the impact of adult separation anxiety and uncertainty intolerance. BMC Women’s Health, 25(1), 377. https://doi.org/10.1186/s12905-025-03930-w
Alkoudsi, K. T., & Basheti, I. A. (2020). Prevalence of anxiety and depression among women with polycystic ovary syndrome living in war versus non-war zone countries: A randomized controlled trial assessing a pharmacist intervention. Research in Social and Administrative Pharmacy, 16(5), 689–698. https://doi.org/10.1016/j.sapharm.2019.08.027
Simon, V., Peigné, M., & Dewailly, D. (2023). The psychosocial impact of polycystic ovary syndrome. Reproductive Medicine, 4(1), 57–64. https://doi.org/10.3390/reprodmed4010007
Daescu, A., Daescu, A.-M. C., Dehelean, L., Navolan, D.-B., Gaitoane, A.-I., & Stoian, D. (2025). Multivariate profiles of female sexual function: A cluster analysis of FSFI domains in women with and without PCOS. Biomedicines, 13(12), 3069. https://doi.org/10.3390/biomedicines13123069
Lalonde-Bester, S., Malik, M., Masoumi, R., Ng, K., Sidhu, S., Ghosh, M., & Vine, D. (2024). Prevalence and etiology of eating disorders in polycystic ovary syndrome: A scoping review. Advances in Nutrition, 15(4), 100193. https://doi.org/10.1016/j.advnut.2024.100193
Lee, I., Cooney, L. G., Saini, S., Sammel, M. D., Allison, K. C., & Dokras, A. (2019). Increased odds of disordered eating in polycystic ovary syndrome: A systematic review and meta-analysis. Eating and Weight Disorders, 24(5), 787–797. https://doi.org/10.1007/s40519-018-0533-y
Góral, A., Żywot, K., Zalewski, W., Jagodziński, A., & Murawski, M. (2024). Polycystic ovary syndrome and eating disorders—A literature review. Journal of Clinical Medicine, 14(1), 27. https://doi.org/10.3390/jcm14010027
Thornburgh, S., Naimi, A. I., Sonneville, K. R., Chavarro, J. E., Howards, P. P., & Gaskins, A. J. (2025). Disordered eating behaviors during adolescence and risk of polycystic ovary syndrome: A prospective cohort study. Journal of Clinical Endocrinology & Metabolism. Advance online publication. https://doi.org/10.1210/clinem/dgaf609
Dhumad, M., Hamdan, F., & Al-Mayah, Q. (2025). Cognitive impairment and associated metabolic and hormonal factors in women with polycystic ovarian syndrome: A Montreal Cognitive Assessment-based case-control study. Italian Journal of Medicine, 19. https://doi.org/10.4081/itjm.2025.2085
Agarwal, T., & Singh, S. (2025). The interplay between cognitive impairment and mental health in women with PCOS: A systematic review. International Journal of Research in Medical Sciences, 13, 3429–3437. https://doi.org/10.18203/2320-6012.ijrms20252416
Shafti, V., & Shahbazi, S. (2016). Comparing sexual function and quality of life in polycystic ovary syndrome and healthy women. Journal of Family and Reproductive Health, 10(2), 92–98.
Ligocka, N., Chmaj-Wierzchowska, K., Wszołek, K., Wilczak, M., & Tomczyk, K. (2024). Quality of life of women with polycystic ovary syndrome. Medicina, 60(2), 294. https://doi.org/10.3390/medicina60020294
Huddleston, H. G., Milani, A., & Blank, R. (2024). Productivity loss due to polycystic ovary syndrome and its relationship to race, mental health and healthcare delivery indices. F&S Reports, 5(2), 157–163. https://doi.org/10.1016/j.xfre.2024.02.004
Azarbayjani, K., Sadatmahalleh, S. J., Mirzaei, N., Yarjanly, M., Jahangiri, N., Nasiri, M., & Zeinaloo, M. (2025). Comparison of sexual function in fertile and infertile women with polycystic ovary syndrome: A cross-sectional study. International Journal of Reproductive BioMedicine, 23(9), 739–748. https://doi.org/10.18502/ijrm.v23i9.20161
Daescu, A., Daescu, A.-M. C., Dehelean, L., Navolan, D.-B., Gaitoane, A.-I., & Stoian, D. (2025). Multivariate profiles of female sexual function: A cluster analysis of FSFI domains in women with and without PCOS. Biomedicines, 13(12), 3069. https://doi.org/10.3390/biomedicines13123069
Alsaidan, A. A., Thirunavukkarasu, A., & Alsulami, H. H. (2025). Body shape concerns, sexual satisfaction, and associated factors among patients with polycystic ovarian syndrome: A cross-sectional study in Western Saudi Arabia. Saudi Medical Journal, 46(1), 94–101. https://doi.org/10.15537/smj.2025.46.1.20240797
Tang, R., Yang, J., Yu, Y., & Fang, Y. (2022). The effects of cognitive behavioral therapy in women with polycystic ovary syndrome: A meta-analysis. Frontiers in Psychology, 13, 796594. https://doi.org/10.3389/fpsyg.2022.796594
Wang, G., Guan, M., Li, R., He, T., Luo, L., Hu, S., Wang, B., Liu, D., & Lei, J. (2025). Impact of combined mindfulness-integrated cognitive behavior therapy and lifestyle interventions on mental health in women with polycystic ovary syndrome: A randomized controlled trial. Mindfulness. https://doi.org/10.1007/s12671-025-02717-2
Kabiri, S. S., Javanbakht, Z., Zangeneh, M., Moludi, J., Saber, A., Salimi, Y., Tandorost, A., & Jamalpour, M. (2024). The effects of MIND diet on depression, anxiety, quality of life and metabolic and hormonal status in obese or overweight women with polycystic ovary syndrome: A randomised clinical trial. British Journal of Nutrition. Advance online publication. https://doi.org/10.1017/S0007114524001168
Scannell, N., Mantzioris, E., Cowan, S., Moran, L., & Villani, A. (2025). A pilot randomized control trial evaluating the feasibility of a 12-week Mediterranean diet intervention without caloric restriction in women with polycystic ovary syndrome. Journal of Clinical Medicine, 14(16), 5842. https://doi.org/10.3390/jcm14165842
Gautam, R., Maan, P., Jyoti, A., Kumar, A., Malhotra, N., & Arora, T. (2025). The role of lifestyle interventions in PCOS management: A systematic review. Nutrients, 17(2), 310. https://doi.org/10.3390/nu17020310
Woodward, A., Klonizakis, M., & Broom, D. (2020). Exercise and polycystic ovary syndrome. Advances in Experimental Medicine and Biology, 1228, 123–136. https://doi.org/10.1007/978-981-15-1792-1_8
Murawska-Ciałowicz, E., Wiatr, M., Ciałowicz, M., Gomes de Assis, G., Borowicz, W., Rocha-Rodrigues, S., Paprocka-Borowicz, M., & Marques, A. (2021). BDNF impact on biological markers of depression—Role of physical exercise and training. International Journal of Environmental Research and Public Health, 18(14), 7553. https://doi.org/10.3390/ijerph18147553
Mouawad, M., Nabipur, L., & Agrawal, D. K. (2025). Impact of antidepressants on weight gain: Underlying mechanisms and mitigation strategies. Archives of Clinical and Biomedical Research, 9(3), 183–195.
U.S. Preventive Services Task Force. (2023). Screening for depression and suicide risk in adults: US Preventive Services Task Force recommendation statement. JAMA, 329(23), 2057–2067. https://doi.org/10.1001/jama.2023.9297
Bachega, F. S., Turri, J. A. O., Baracat, M. C. P., Simões, R. S., Maciel, G. A. R., Lobo, R. A., Soares, J. M., Jr., & Baracat, E. C. (2025). New comprehension on polycystic ovary syndrome and sexual function: A systematic review and meta-analysis. Journal of Sexual Medicine, 22(9), 1612–1628. https://doi.org/10.1093/jsxmed/qdaf163
Daescu, A., Daescu, A.-M. C., Dehelean, L., Navolan, D.-B., Gaitoane, A.-I., & Stoian, D. (2025). Multivariate profiles of female sexual function: A cluster analysis of FSFI domains in women with and without PCOS. Biomedicines, 13(12), 3069. https://doi.org/10.3390/biomedicines13123069
Coffey, S., Bano, G., & Mason, H. D. (2006). Health-related quality of life in women with polycystic ovary syndrome: A comparison with the general population using the Polycystic Ovary Syndrome Questionnaire (PCOSQ) and the Short Form-36 (SF-36). Gynecological Endocrinology, 22(2), 80–86. https://doi.org/10.1080/09513590600604541
Alberta Health Services. (2025). Provincial PCOS primary care clinical pathway. https://www.albertahealthservices.ca/assets/info/aph/if-aph-prov-pcos-primary-care-clinical-pathway.pdf
Markowicz-Piasecka, M., Sikora, J., Szydłowska, A., Skupień, A., Mikiciuk-Olasik, E., & Huttunen, K. M. (2017). Metformin—A future therapy for neurodegenerative diseases. Pharmaceutical Research, 34(12), 2614–2627. https://doi.org/10.1007/s11095-017-2199-y
Demaré, S., Kothari, A., Calcutt, N. A., & Fernyhough, P. (2021). Metformin as a potential therapeutic for neurological disease: Mobilizing AMPK to repair the nervous system. Expert Review of Neurotherapeutics, 21(1), 45–63. https://doi.org/10.1080/14737175.2021.1847645
Brand, K. M., Gottwald-Hostalek, U., & Andag-Silva, A. (2025). Update on the therapeutic role of metformin in the management of polycystic ovary syndrome: Effects on pathophysiologic process and fertility outcomes. Women’s Health, 21, 17455057241311759. https://doi.org/10.1177/17455057241311759
Saadati, S., Mason, T., Godini, R., Vanky, E., Teede, H., & Mousa, A. (2025). Metformin use in women with polycystic ovary syndrome (PCOS): Opportunities, benefits, and clinical challenges. Diabetes, Obesity and Metabolism, 27(Suppl. 3), 31–47. https://doi.org/10.1111/dom.16422
Zeng, W., Luo, Y., Ou, J., Gan, D., Huang, M., Tomlinson, B., & Jiang, Y. (2025). Metformin in polycystic ovary syndrome: Unraveling multi-stage therapeutic mechanisms from puberty to long-term health outcomes. Frontiers in Pharmacology, 16, 1654372. https://doi.org/10.3389/fphar.2025.1654372
Unfer, V., Facchinetti, F., Orrù, B., Giordani, B., & Nestler, J. (2017). Myo-inositol effects in women with PCOS: A meta-analysis of randomized controlled trials. Endocrine Connections, 6(8), 647–658. https://doi.org/10.1530/EC-17-0243
Cantelmi, T., Lambiase, E., Unfer, V. R., Gambioli, R., & Unfer, V. (2021). Inositol treatment for psychological symptoms in polycystic ovary syndrome women. European Review for Medical and Pharmacological Sciences, 25(5), 2383–2389. https://doi.org/10.26355/eurrev_202103_25278
Greff, D., Juhász, A. E., Váncsa, S., Váradi, A., Sipos, Z., Szinte, J., Park, S., Hegyi, P., Nyirády, P., Ács, N., Várbíró, S., & Horváth, E. M. (2023). Inositol is an effective and safe treatment in polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials. Reproductive Biology and Endocrinology, 21(1), 10. https://doi.org/10.1186/s12958-023-01055-z
Chengappa, K. N., Levine, J., Gershon, S., Mallinger, A. G., Hardan, A., Vagnucci, A., Pollock, B., Luther, J., Buttenfield, J., Verfaille, S., & Kupfer, D. J. (2000). Inositol as an add-on treatment for bipolar depression. Bipolar Disorders, 2(1), 47–55. https://doi.org/10.1034/j.1399-5618.2000.020107.x
Ciarcia, J., & Huckins, L. M. (2024). Oral contraceptives and the risk of psychiatric side effects: A review. Complex Psychiatry, 10(1–4), 36–44. https://doi.org/10.1159/000539515
Mengelkoch, S., Afshar, K., & Slavich, G. M. (2025). Hormonal contraceptive use and affective disorders: An updated review. Open Access Journal of Contraception, 16, 1–29. https://doi.org/10.2147/OAJC.S431365
Mouawad, M., Nabipur, L., & Agrawal, D. K. (2025). Impact of antidepressants on weight gain: Underlying mechanisms and mitigation strategies. Archives of Clinical and Biomedical Research, 9(3), 183–195.
Masoudi, M., Ansari, S., Kashani, L., Tavolinejad, H., Hossein Rashidi, B., Esalatmanesh, S., Ghazizadeh-Hashemi, M., Noorbala, A. A., & Akhondzadeh, S. (2021). Effect of sertraline on depression severity and prolactin levels in women with polycystic ovary syndrome: A placebo-controlled randomized trial. International Clinical Psychopharmacology, 36(5), 238–243. https://doi.org/10.1097/YIC.0000000000000367
Bashir, R., Asrar, M. M., Shah, I. A., Wani, I. A., & Ganie, M. A. (2023). Do pleiotropic effects of spironolactone in women with PCOS make it more than an anti-androgen? Evidence from a systematic review and meta-analysis. Current Pharmaceutical Design, 29(19), 1486–1496. https://doi.org/10.2174/1381612829666230331093912
Vargas-Mora, P., & Morgado-Carrasco, D. (2020). Spironolactone in dermatology: Uses in acne, hidradenitis suppurativa, female pattern baldness, and hirsutism. Actas Dermo-Sifiliográficas, 111(8), 639–649. https://doi.org/10.1016/j.ad.2020.03.001
Leelaphiwat, S., Jongwutiwes, T., Lertvikool, S., Tabcharoen, C., Sukprasert, M., Rattanasiri, S., & Weerakiet, S. (2015). Comparison of desogestrel/ethinyl estradiol plus spironolactone versus cyproterone acetate/ethinyl estradiol in the treatment of polycystic ovary syndrome: A randomized controlled trial. Journal of Obstetrics and Gynaecology Research, 41(3), 402–410. https://doi.org/10.1111/jog.12543
Shams, M., Sattarinezhad, A., Rostamipour, H., Purkhosrow, A., & Sattarinezhad, E. (2025). Comparison of the effects of cyproterone compound-spironolactone, metformin and pioglitazone on serum levels of high sensitivity C-reactive protein and complement system in polycystic ovarian syndrome: A randomized double-blind clinical trial. Reviews in Clinical Medicine, 12(1), 41–48. https://doi.org/10.22038/rcm.2025.84411.1518
Kar, S. (2012). Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial. Journal of Human Reproductive Sciences, 5(3), 262–265. https://doi.org/10.4103/0974-1208.106338
Vajna, R. Z., Géczi, A. M., Meznerics, F. A., Ács, N., Hegyi, P., Feig, E. Z., Fehérvári, P., Kiss-Dala, S., Várbíró, S., Hetthessy, J. R., & Sára, L. (2024). Strong early impact of letrozole on ovulation induction outperforms clomiphene citrate in polycystic ovary syndrome. Pharmaceuticals, 17(7), 971. https://doi.org/10.3390/ph17070971
Wasim, T., Nasrin, T., Zunair, J., & Irshad, S. (2024). Efficacy of letrozole vs clomiphene citrate for induction of ovulation in women with polycystic ovarian syndrome. Pakistan Journal of Medical Sciences, 40(1, Part I), 78–83. https://doi.org/10.12669/pjms.40.1.7971
Legro, R. S., Brzyski, R. G., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Casson, P., Christman, G. M., Huang, H., Yan, Q., Alvero, R., Haisenleder, D. J., Barnhart, K. T., Bates, G. W., Usadi, R., Lucidi, S., Baker, V., Trussell, J. C., Krawetz, S. A., Snyder, P., ... NICHD Reproductive Medicine Network. (2014). Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. New England Journal of Medicine, 371(2), 119–129. https://doi.org/10.1056/NEJMoa1313517
Kar, S. (2012). Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial. Journal of Human Reproductive Sciences, 5(3), 262–265. https://doi.org/10.4103/0974-1208.106338
Karam, R. A., Gharib, A. F., Alrehaili, A. A., Bakhuraysah, M. M., Alhuthali, H. M., Saber, T., & Abdelrahman, T. M. (2025). Association of vitamin D with depression and anxiety in polycystic ovary syndrome in Saudi Arabia. Journal of Family Medicine and Primary Care, 14(9), 3703–3710. https://doi.org/10.4103/jfmpc.jfmpc_1991_24
Kelaiditis, C. F., Gibson, E. L., & Dyall, S. C. (2023). Effects of long-chain omega-3 polyunsaturated fatty acids on reducing anxiety and/or depression in adults: A systematic review and meta-analysis of randomised controlled trials. Prostaglandins, Leukotrienes and Essential Fatty Acids, 192, 102572. https://doi.org/10.1016/j.plefa.2023.102572
Yang, K., Zeng, L., Bao, T., & Ge, J. (2018). Effectiveness of omega-3 fatty acid for polycystic ovary syndrome: A systematic review and meta-analysis. Reproductive Biology and Endocrinology, 16(1), 27. https://doi.org/10.1186/s12958-018-0346-x
Viña, I., Viña, J. R., Carranza, M., & Mariscal, G. (2025). Efficacy of N-acetylcysteine in polycystic ovary syndrome: Systematic review and meta-analysis. Nutrients, 17(2), 284. https://doi.org/10.3390/nu17020284
Thakker, D., Raval, A., Patel, I., & Walia, R. (2015). N-acetylcysteine for polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled clinical trials. Obstetrics and Gynecology International, 2015, 817849. https://doi.org/10.1155/2015/817849
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Maciej Ficek, Wojciech Gawęda, Wiktoria Łobodzińska, Zuzanna Hamouta, Justyna Adamczyk

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

