Polycystic ovary syndrome.
Journal
Nature reviews. Disease primers
ISSN: 2056-676X
Titre abrégé: Nat Rev Dis Primers
Pays: England
ID NLM: 101672103
Informations de publication
Date de publication:
18 Apr 2024
18 Apr 2024
Historique:
accepted:
18
03
2024
medline:
19
4
2024
pubmed:
19
4
2024
entrez:
18
4
2024
Statut:
epublish
Résumé
Despite affecting ~11-13% of women globally, polycystic ovary syndrome (PCOS) is a substantially understudied condition. PCOS, possibly extending to men's health, imposes a considerable health and economic burden worldwide. Diagnosis in adults follows the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome, requiring two out of three criteria - clinical or biochemical hyperandrogenism, ovulatory dysfunction, and/or specific ovarian morphological characteristics or elevated anti-Müllerian hormone. However, diagnosing adolescents omits ovarian morphology and anti-Müllerian hormone considerations. PCOS, marked by insulin resistance and hyperandrogenism, strongly contributes to early-onset type 2 diabetes, with increased odds for cardiovascular diseases. Reproduction-related implications include irregular menstrual cycles, anovulatory infertility, heightened risks of pregnancy complications and endometrial cancer. Beyond physiological manifestations, PCOS is associated with anxiety, depression, eating disorders, psychosexual dysfunction and negative body image, collectively contributing to diminished health-related quality of life in patients. Despite its high prevalence persisting into menopause, diagnosing PCOS often involves extended timelines and multiple health-care visits. Treatment remains ad hoc owing to limited understanding of underlying mechanisms, highlighting the need for research delineating the aetiology and pathophysiology of the syndrome. Identifying factors contributing to PCOS will pave the way for personalized medicine approaches. Additionally, exploring novel biomarkers, refining diagnostic criteria and advancing treatment modalities will be crucial in enhancing the precision and efficacy of interventions that will positively impact the lives of patients.
Identifiants
pubmed: 38637590
doi: 10.1038/s41572-024-00511-3
pii: 10.1038/s41572-024-00511-3
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
27Informations de copyright
© 2024. Springer Nature Limited.
Références
Teede, H. J. et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Fertil. Steril. https://doi.org/10.1016/j.fertnstert.2023.07.025 (2023).
doi: 10.1016/j.fertnstert.2023.07.025
pubmed: 37589624
Azziz, R., Marin, C., Hoq, L., Badamgarav, E. & Song, P. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J. Clin. Endocrinol. Metab. 90, 4650–4658 (2005).
pubmed: 15944216
doi: 10.1210/jc.2005-0628
Riestenberg, C., Jagasia, A., Markovic, D., Buyalos, R. P. & Azziz, R. Health care-related economic burden of polycystic ovary syndrome in the United States: pregnancy-related and long-term health consequences. J. Clin. Endocrinol. Metab. 107, 575–585 (2022). This paper highlights that early diagnosis and interventions could possibly reduce the risk of developing comorbidities and the health-care-related economic burden of PCOS.
pubmed: 34546364
doi: 10.1210/clinem/dgab613
Yadav, S. et al. Direct economic burden of mental health disorders associated with Polycystic ovary syndrome: systematic review and meta-analysis. eLife 12, e85338 (2023).
pubmed: 37534878
pmcid: 10471160
doi: 10.7554/eLife.85338
Liu, Q. et al. A genome-wide cross-trait analysis identifies shared loci and causal relationships of type 2 diabetes and glycaemic traits with polycystic ovary syndrome. Diabetologia 65, 1483–1494 (2022).
pubmed: 35771237
pmcid: 9345824
doi: 10.1007/s00125-022-05746-x
Ruth, K. S. et al. Using human genetics to understand the disease impacts of testosterone in men and women. Nat. Med. 26, 252–258 (2020).
pubmed: 32042192
pmcid: 7025895
doi: 10.1038/s41591-020-0751-5
Long, C. et al. Prevalence of polycystic ovary syndrome in patients with type 2 diabetes: a systematic review and meta-analysis. Front. Endocrinol. 13, 980405 (2022).
doi: 10.3389/fendo.2022.980405
Cooney, L. G. & Dokras, A. Cardiometabolic risk in polycystic ovary syndrome: current guidelines. Endocrinol. Metab. Clin. North Am. 50, 83–95 (2021).
pubmed: 33518188
doi: 10.1016/j.ecl.2020.11.001
Hoeger, K. M., Dokras, A. & Piltonen, T. Update on PCOS: consequences, challenges, and guiding treatment. J. Clin. Endocrinol. Metab. 106, e1071–e1083 (2021).
pubmed: 33211867
doi: 10.1210/clinem/dgaa839
Zhuang, C. et al. Cardiovascular risk according to body mass index in women of reproductive age with polycystic ovary syndrome: a systematic review and meta-analysis. Front. Cardiovasc. Med. 9, 822079 (2022).
pubmed: 35252398
pmcid: 8893173
doi: 10.3389/fcvm.2022.822079
Ollila, M. M., Hoek, A. & Piltonen, T. T. The association between polycystic ovary syndrome and early cardiovascular disease morbidity strengthens. Eur. J. Endocrinol. 189, R4–R5 (2023).
pubmed: 37461221
doi: 10.1093/ejendo/lvad083
Berni, T. R., Morgan, C. L. & Rees, D. A. Women with polycystic ovary syndrome have an increased risk of major cardiovascular events: a population study. J. Clin. Endocrinol. Metab. 106, e3369–e3380 (2021). This study shows that women with PCOS have a higher incidence of myocardial infarction, angina pectoris and revascularization.
pubmed: 34061968
pmcid: 8372630
doi: 10.1210/clinem/dgab392
Millan-de-Meer, M., Luque-Ramirez, M., Nattero-Chavez, L. & Escobar-Morreale, H. F. PCOS during the menopausal transition and after menopause: a systematic review and meta-analysis. Hum. Reprod. Update 29, 741–772 (2023).
pubmed: 37353908
doi: 10.1093/humupd/dmad015
van der Ham, K. et al. Change in androgenic status and cardiometabolic profile of middle-aged women with polycystic ovary syndrome. J. Clin. Med. 12, 5226 (2023).
pubmed: 37629271
pmcid: 10455407
doi: 10.3390/jcm12165226
Johnson, J. E., Daley, D., Tarta, C. & Stanciu, P. I. Risk of endometrial cancer in patients with polycystic ovarian syndrome: a meta-analysis. Oncol. Lett. 25, 168 (2023). This study shows that women with PCOS have a fivefold increased risk of developing endometrial cancer.
pubmed: 36960190
pmcid: 10028221
doi: 10.3892/ol.2023.13754
Hanna, F., Wu, P., Heald, A. & Fryer, A. Diabetes detection in women with gestational diabetes and polycystic ovarian syndrome. BMJ 382, e071675 (2023).
pubmed: 37402524
doi: 10.1136/bmj-2022-071675
Mills, G., Badeghiesh, A., Suarthana, E., Baghlaf, H. & Dahan, M. H. Polycystic ovary syndrome as an independent risk factor for gestational diabetes and hypertensive disorders of pregnancy: a population-based study on 9.1 million pregnancies. Hum. Reprod. 35, 1666–1674 (2020). This study shows that women with PCOS have an increased risk for pregnancy complications, including gestational diabetes and hypertension, independent of coexisting metabolic conditions.
pubmed: 32535629
doi: 10.1093/humrep/deaa099
Gibson-Helm, M., Teede, H., Dunaif, A. & Dokras, A. Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 102, 604–612 (2017).
pubmed: 27906550
Dapas, M. & Dunaif, A. Deconstructing a syndrome: genomic insights into PCOS causal mechanisms and classification. Endocr. Rev. 43, 927–965 (2022).
pubmed: 35026001
pmcid: 9695127
doi: 10.1210/endrev/bnac001
Leinonen, J. T. et al. Genetic analyses implicate complex links between adult testosterone levels and health and disease. Commun. Med. 3, 4 (2023).
pubmed: 36653534
pmcid: 9849476
doi: 10.1038/s43856-022-00226-0
Xue, A. et al. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat. Commun. 9, 2941 (2018).
pubmed: 30054458
pmcid: 6063971
doi: 10.1038/s41467-018-04951-w
Davitadze, M. et al. Body image concerns in women with polycystic ovary syndrome: a systematic review and meta-analysis. Eur. J. Endocrinol. 189, R1–R9 (2023).
pubmed: 37619990
doi: 10.1093/ejendo/lvad110
Nasiri-Amiri, F., Faramarzi, M., Omidvar, S. & Alizadeh-Navaei, R. Depression and anxiety in adolescents and young women with polycystic ovary syndrome: a systematic review and meta-analysis. Int. J. Adolesc. Med. Health 35, 233–242 (2023).
pubmed: 37158791
doi: 10.1515/ijamh-2022-0065
Mousa, A., Thien Tay, C. & Teede, H. Technical Report for the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome https://doi.org/10.26180/23625288.v1 (Monash University, 2023).
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril. 81, 19–25 (2004).
doi: 10.1016/j.fertnstert.2003.10.004
Lizneva, D. et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil. Steril. 106, 6–15 (2016).
pubmed: 27233760
doi: 10.1016/j.fertnstert.2016.05.003
March, W. A. et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum. Reprod. 25, 544–551 (2010).
pubmed: 19910321
doi: 10.1093/humrep/dep399
Piltonen, T. T. et al. AMH as part of the diagnostic PCOS workup in large epidemiological studies. Eur. J. Endocrinol. 188, 547–554 (2023).
pubmed: 37294941
doi: 10.1093/ejendo/lvad065
Wu, Q., Gao, J., Bai, D., Yang, Z. & Liao, Q. The prevalence of polycystic ovarian syndrome in Chinese women: a meta-analysis. Ann. Palliat. Med. 10, 74–87 (2021).
pubmed: 33545750
doi: 10.21037/apm-20-1893
Moran, C., Arriaga, M., Rodriguez, G. & Moran, S. Obesity differentially affects phenotypes of polycystic ovary syndrome. Int. J. Endocrinol. 2012, 317241 (2012).
pubmed: 22829818
pmcid: 3399368
doi: 10.1155/2012/317241
Teede, H. J. et al. Longitudinal weight gain in women identified with polycystic ovary syndrome: results of an observational study in young women. Obesity 21, 1526–1532 (2013).
pubmed: 23818329
doi: 10.1002/oby.20213
Kataoka, J. et al. Prevalence of polycystic ovary syndrome in women with severe obesity — effects of a structured weight loss programme. Clin. Endocrinol. 91, 750–758 (2019). This study demonstrates that the prevalence of PCOS increases up to 25% with severe obesity.
doi: 10.1111/cen.14098
van Keizerswaard, J., Dietz de Loos, A. L. P., Louwers, Y. V. & Laven, J. S. E. Changes in individual polycystic ovary syndrome phenotypical characteristics over time: a long-term follow-up study. Fertil. Steril. 117, 1059–1066 (2022).
pubmed: 35219451
doi: 10.1016/j.fertnstert.2022.01.014
Kujanpaa, L. et al. Women with polycystic ovary syndrome are burdened with multimorbidity and medication use independent of body mass index at late fertile age: a population-based cohort study. Acta Obstet. Gynecol. Scand. 101, 728–736 (2022).
pubmed: 35673942
pmcid: 9564432
doi: 10.1111/aogs.14382
Ollila, M. M. et al. Women with PCOS have an increased risk for cardiovascular disease regardless of diagnostic criteria-a prospective population-based cohort study. Eur. J. Endocrinol. 189, 96–105 (2023).
pubmed: 37436934
doi: 10.1093/ejendo/lvad077
Ollila, M. M. et al. Weight gain and dyslipidemia in early adulthood associate with polycystic ovary syndrome: prospective cohort study. J. Clin. Endocrinol. Metab. 101, 739–747 (2016).
pubmed: 26652764
doi: 10.1210/jc.2015-3543
Hagberg, C. E. & Spalding, K. L. White adipocyte dysfunction and obesity-associated pathologies in humans. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-023-00680-1 (2023).
doi: 10.1038/s41580-023-00680-1
pubmed: 38086922
Lim, S. S., Davies, M. J., Norman, R. J. & Moran, L. J. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update 18, 618–637 (2012).
pubmed: 22767467
doi: 10.1093/humupd/dms030
Koivuaho, E. et al. Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood-longitudinal analysis of BMI data from birth to age 46 in cases of PCOS. Int. J. Obes. 43, 1370–1379 (2019). This study demonstrates that early weight gain in childhood plays a crucial role in the emerging PCOS, highlighting the importance of early preventive interventions against metabolic disorders.
doi: 10.1038/s41366-019-0318-z
Kakoly, N. S., Earnest, A., Moran, L. J., Teede, H. J. & Joham, A. E. Group-based developmental BMI trajectories, polycystic ovary syndrome, and gestational diabetes: a community-based longitudinal study. BMC Med. 15, 195 (2017).
pubmed: 29110650
pmcid: 5674239
doi: 10.1186/s12916-017-0957-7
Sendur, S. N. & Yildiz, B. O. Influence of ethnicity on different aspects of polycystic ovary syndrome: a systematic review. Reprod. Biomed. Online 42, 799–818 (2021).
pubmed: 33487557
doi: 10.1016/j.rbmo.2020.12.006
Kim, J. J. & Choi, Y. M. Phenotype and genotype of polycystic ovary syndrome in Asia: ethnic differences. J. Obstet. Gynaecol. Res. 45, 2330–2337 (2019).
pubmed: 31588677
doi: 10.1111/jog.14132
Ramezani Tehrani, F., Behboudi-Gandevani, S., Bidhendi Yarandi, R., Saei Ghare Naz, M. & Carmina, E. Prevalence of acne vulgaris among women with polycystic ovary syndrome: a systemic review and meta-analysis. Gynecol. Endocrinol. 37, 392–405 (2021).
pubmed: 33355023
doi: 10.1080/09513590.2020.1859474
Carmina, E. et al. Female pattern hair loss and androgen excess: a report from the multidisciplinary androgen excess and PCOS committee. J. Clin. Endocrinol. Metab. 104, 2875–2891 (2019).
pubmed: 30785992
doi: 10.1210/jc.2018-02548
Karjula, S. et al. Psychological distress is more prevalent in fertile age and premenopausal women with PCOS symptoms: 15-year follow-up. J. Clin. Endocrinol. Metab. 102, 1861–1869 (2017).
pubmed: 28323926
pmcid: 5470769
doi: 10.1210/jc.2016-3863
Cassar, S. et al. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies. Hum. Reprod. 31, 2619–2631 (2016).
pubmed: 27907900
doi: 10.1093/humrep/dew243
Stepto, N. K. et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum. Reprod. 28, 777–784 (2013). Although insulin resistance is present independently of BMI, this study highlights that insulin resistance worsens by increased BMI irrespective of visceral fat accumulation, supporting inherent insulin resistance.
pubmed: 23315061
doi: 10.1093/humrep/des463
Pelanis, R. et al. The prevalence of type 2 diabetes is not increased in normal-weight women with PCOS. Hum. Reprod. 32, 2279–2286 (2017).
pubmed: 29040530
doi: 10.1093/humrep/dex294
Wekker, V. et al. Long-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis. Hum. Reprod. Update 26, 942–960 (2020).
pubmed: 32995872
pmcid: 7600286
doi: 10.1093/humupd/dmaa029
Ollila, M. M. et al. OR35-06 polycystic ovary syndrome is associated with an increased mortality risk. J. Endocr. Soc. 7, bvad114.1712 (2023).
pmcid: 10554621
doi: 10.1210/jendso/bvad114.1712
Kasarinaite, A., Sinton, M., Saunders, P. T. K. & Hay, D. C. The influence of sex hormones in liver function and disease. Cells 12, 1604 (2023).
pubmed: 37371074
pmcid: 10296738
doi: 10.3390/cells12121604
Rinella, M. E. et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J. Hepatol. 79, 1542–1556 (2023).
pubmed: 37364790
doi: 10.1016/j.jhep.2023.06.003
Manzano-Nunez, R. et al. Non-alcoholic fatty liver disease in patients with polycystic ovary syndrome: a systematic review, meta-analysis, and meta-regression. J. Clin. Med. 12, 856 (2023). This study shows that women with PCOS already at a young age have an increased prevalence of MASLD.
pubmed: 36769504
pmcid: 9917911
doi: 10.3390/jcm12030856
Joham, A. E., Teede, H. J., Ranasinha, S., Zoungas, S. & Boyle, J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. J. Womens Health 24, 299–307 (2015).
doi: 10.1089/jwh.2014.5000
West, S. et al. The impact of self-reported oligo-amenorrhea and hirsutism on fertility and lifetime reproductive success: results from the Northern Finland Birth Cohort 1966. Hum. Reprod. 29, 628–633 (2014).
pubmed: 24324025
doi: 10.1093/humrep/det437
Persson, S. et al. Fecundity among women with polycystic ovary syndrome (PCOS) — a population-based study. Hum. Reprod. 34, 2052–2060 (2019).
pubmed: 31504532
doi: 10.1093/humrep/dez159
Haase, C. L., Varbo, A., Laursen, P. N., Schnecke, V. & Balen, A. H. Association between body mass index, weight loss and the chance of pregnancy in women with polycystic ovary syndrome and overweight or obesity: a retrospective cohort study in the UK. Hum. Reprod. 38, 471–481 (2023).
pubmed: 36637246
pmcid: 9977115
doi: 10.1093/humrep/deac267
Bahri Khomami, M. et al. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity-a systematic review, meta-analysis, and meta-regression. Obes. Rev. 20, 659–674 (2019).
pubmed: 30674081
doi: 10.1111/obr.12829
Ahmed, M., Shellenberger, J. & Velez, M. P. Polycystic ovary syndrome, gestational diabetes mellitus, and the mediating role of obesity: a population-based cohort study. J. Obstet. Gynaecol. Can. 46, 102238 (2023).
pubmed: 37827332
doi: 10.1016/j.jogc.2023.102238
Chen, X., Gissler, M. & Lavebratt, C. Association of maternal polycystic ovary syndrome and diabetes with preterm birth and offspring birth size: a population-based cohort study. Hum. Reprod. 37, 1311–1323 (2022).
pubmed: 35348682
pmcid: 9156851
doi: 10.1093/humrep/deac050
Alur-Gupta, S., Boland, M. R., Barnhart, K. T., Sammel, M. D. & Dokras, A. Postpartum complications increased in women with polycystic ovary syndrome. Am. J. Obstet. Gynecol. 224, 280.e1–280.e13 (2021).
pubmed: 32835722
doi: 10.1016/j.ajog.2020.08.048
Pastoor, H., Both, S., Laan, E. T. M. & Laven, J. S. E. Sexual dysfunction in women with PCOS: a case control study. Hum. Reprod. 38, 2230–2238 (2023). This study shows that women with the syndrome suffer from impaired sexual function with minimal impact of endocrine dysfunction, highlighting the importance of psychosexual counselling.
pubmed: 37776157
pmcid: 10628505
doi: 10.1093/humrep/dead193
Glintborg, D., Hass Rubin, K., Nybo, M., Abrahamsen, B. & Andersen, M. Morbidity and medicine prescriptions in a nationwide Danish population of patients diagnosed with polycystic ovary syndrome. Eur. J. Endocrinol. 172, 627–638 (2015).
pubmed: 25656495
doi: 10.1530/EJE-14-1108
Beavis, A. L. et al. Identifying women 45 years and younger at elevated risk for endometrial hyperplasia or cancer. Gynecol. Oncol. 174, 98–105 (2023).
pubmed: 37172411
doi: 10.1016/j.ygyno.2023.04.019
Lu, L., Luo, J., Deng, J., Huang, C. & Li, C. Polycystic ovary syndrome is associated with a higher risk of premalignant and malignant endometrial polyps in premenopausal women: a retrospective study in a tertiary teaching hospital. BMC Womens Health 23, 127 (2023).
pubmed: 36964546
pmcid: 10037815
doi: 10.1186/s12905-023-02269-4
Zhu, T., Cui, J. & Goodarzi, M. O. Polycystic ovary syndrome and breast cancer subtypes: a Mendelian randomization study. Am. J. Obstet. Gynecol. 225, 99–101 (2021).
pubmed: 33771497
doi: 10.1016/j.ajog.2021.03.020
Wu, P. F. et al. Polycystic ovary syndrome is causally associated with estrogen receptor-positive instead of estrogen receptor-negative breast cancer: a Mendelian randomization study. Am. J. Obstet. Gynecol. 223, 583–585 (2020).
pubmed: 32413428
doi: 10.1016/j.ajog.2020.05.016
Amiri, M., Bidhendi-Yarandi, R., Fallahzadeh, A., Marzban, Z. & Ramezani Tehrani, F. Risk of endometrial, ovarian, and breast cancers in women with polycystic ovary syndrome: a systematic review and meta-analysis. Int. J. Reprod. Biomed. 20, 893–914 (2022).
pubmed: 36618838
pmcid: 9806243
Barry, J. A., Azizia, M. M. & Hardiman, P. J. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update 20, 748–758 (2014).
pubmed: 24688118
pmcid: 4326303
doi: 10.1093/humupd/dmu012
Greenwood, E. A., Yaffe, K., Wellons, M. F., Cedars, M. I. & Huddleston, H. G. Depression over the lifespan in a population-based cohort of women with polycystic ovary syndrome: longitudinal analysis. J. Clin. Endocrinol. Metab. 104, 2809–2819 (2019).
pubmed: 30985868
pmcid: 6534493
doi: 10.1210/jc.2019-00234
Dwivedi, A. K., Vishwakarma, D., Dubey, P. & Reddy, S. Association of polycystic ovary syndrome with cardiovascular disease among female hospitalizations in the United States. Eur. J. Endocrinol. 188, 555–563 (2023).
pubmed: 37307574
doi: 10.1093/ejendo/lvad067
Zhang, J., Xu, J. H., Qu, Q. Q. & Zhong, G. Q. Risk of cardiovascular and cerebrovascular events in polycystic ovarian syndrome women: a meta-analysis of cohort studies. Front. Cardiovasc. Med. 7, 552421 (2020).
pubmed: 33282917
pmcid: 7690560
doi: 10.3389/fcvm.2020.552421
Forslund, M., Schmidt, J., Brannstrom, M., Landin-Wilhelmsen, K. & Dahlgren, E. Morbidity and mortality in PCOS: a prospective follow-up up to a mean age above 80 years. Eur. J. Obstet. Gynecol. Reprod. Biol. 271, 195–203 (2022).
pubmed: 35220175
doi: 10.1016/j.ejogrb.2022.02.020
Merz, C. N. et al. Cardiovascular disease and 10-year mortality in postmenopausal women with clinical features of polycystic ovary syndrome. J. Womens Health 25, 875–881 (2016).
doi: 10.1089/jwh.2015.5441
Legro, R. S. et al. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc. Natl Acad. Sci. USA 95, 14956–14960 (1998).
pubmed: 9843997
pmcid: 24557
doi: 10.1073/pnas.95.25.14956
Vink, J. M., Sadrzadeh, S., Lambalk, C. B. & Boomsma, D. I. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J. Clin. Endocrinol. Metab. 91, 2100–2104 (2006). This study demonstrates a strong contribution of familial factors to PCOS by using data from monozygotic twins.
pubmed: 16219714
doi: 10.1210/jc.2005-1494
Laven, J. S. E. Follicle stimulating hormone receptor (FSHR) polymorphisms and polycystic ovary syndrome (PCOS). Front. Endocrinol. 10, 23 (2019).
doi: 10.3389/fendo.2019.00023
Chen, Z. J. et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat. Genet. 43, 55–59 (2011).
pubmed: 21151128
doi: 10.1038/ng.732
Day, F. R. et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat. Commun. 6, 8464 (2015).
pubmed: 26416764
doi: 10.1038/ncomms9464
Hayes, M. G. et al. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat. Commun. 6, 7502 (2015).
pubmed: 26284813
doi: 10.1038/ncomms8502
Shi, Y. et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat. Genet. 44, 1020–1025 (2012).
pubmed: 22885925
doi: 10.1038/ng.2384
Day, F. et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet. 14, e1007813 (2018).
pubmed: 30566500
pmcid: 6300389
doi: 10.1371/journal.pgen.1007813
Zhang, Y. et al. A genome-wide association study of polycystic ovary syndrome identified from electronic health records. Am. J. Obstet. Gynecol. 223, 559.e1–559.e21 (2020).
pubmed: 32289280
doi: 10.1016/j.ajog.2020.04.004
Tyrmi, J. S. et al. Leveraging Northern European population history: novel low-frequency variants for polycystic ovary syndrome. Hum. Reprod. 37, 352–365 (2022).
pubmed: 34791234
doi: 10.1093/humrep/deab250
Alan Harris, R. et al. Loci on chromosome 12q13.2 encompassing ERBB3, PA2G4 and RAB5B are associated with polycystic ovary syndrome. Gene 852, 147062 (2023).
pubmed: 36423778
doi: 10.1016/j.gene.2022.147062
Waterbury, J. S. et al. The PCOS GWAS candidate gene ZNF217 influences theca cell expression of DENND1A.V2, CYP17A1, and androgen production. J. Endocr. Soc. 6, bvac078 (2022).
pubmed: 35668995
pmcid: 9155636
doi: 10.1210/jendso/bvac078
Zhu, T. & Goodarzi, M. O. Causes and consequences of polycystic ovary syndrome: insights from mendelian randomization. J. Clin. Endocrinol. Metab. 107, e899–e911 (2022).
pubmed: 34669940
doi: 10.1210/clinem/dgab757
Brower, M. A. et al. Bidirectional Mendelian randomization to explore the causal relationships between body mass index and polycystic ovary syndrome. Hum. Reprod. 34, 127–136 (2019).
pubmed: 30496407
doi: 10.1093/humrep/dey343
Zhao, Y. et al. Body mass index and polycystic ovary syndrome: a 2-sample bidirectional mendelian randomization study. J. Clin. Endocrinol. Metab. 105, dgaa125 (2020).
pubmed: 32163573
doi: 10.1210/clinem/dgaa125
Liu, Q. et al. Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis. BMC Med. 20, 66 (2022).
pubmed: 35144605
pmcid: 8832782
doi: 10.1186/s12916-022-02238-y
Zhu, T., Cui, J. & Goodarzi, M. O. Polycystic ovary syndrome and risk of type 2 diabetes, coronary heart disease, and stroke. Diabetes 70, 627–637 (2021).
pubmed: 33158931
doi: 10.2337/db20-0800
Harris, H. R. et al. Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study. Int. J. Epidemiol. 48, 822–830 (2019).
pubmed: 31211375
pmcid: 6659359
doi: 10.1093/ije/dyz113
Goodarzi, M. O. Genetics of common endocrine disease: the present and the future. J. Clin. Endocrinol. Metab. 101, 787–794 (2016).
pubmed: 26908105
pmcid: 4803177
doi: 10.1210/jc.2015-3640
Dapas, M. et al. Distinct subtypes of polycystic ovary syndrome with novel genetic associations: an unsupervised, phenotypic clustering analysis. PLoS Med. 17, e1003132 (2020). Using unsupervised cluster analyses, two distinct subtypes, one reproductive and one metabolic, were identified and they were associated with novel susceptible loci.
pubmed: 32574161
pmcid: 7310679
doi: 10.1371/journal.pmed.1003132
Burns, K. et al. Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry. BMC Genomics 25, 208 (2024).
pubmed: 38408933
pmcid: 10895801
doi: 10.1186/s12864-024-09990-w
Zhu, J. et al. Evidence from men for ovary-independent effects of genetic risk factors for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 107, e1577–e1587 (2022). This study showed that applying a polygenic risk score for PCOS has distinct phenotypic consequences in men.
pubmed: 34969092
doi: 10.1210/clinem/dgab838
Cesta, C. E. et al. Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding? Psychol. Med. 50, 616–624 (2020).
pubmed: 30857571
doi: 10.1017/S0033291719000424
Stener-Victorin, E. & Deng, Q. Epigenetic inheritance of polycystic ovary syndrome — challenges and opportunities for treatment. Nat. Rev. Endocrinol. 17, 521–533 (2021).
pubmed: 34234312
doi: 10.1038/s41574-021-00517-x
Kent, J. et al. Gestational weight gain in women with polycystic ovary syndrome: a controlled study. J. Clin. Endocrinol. Metab. 103, 4315–4323 (2018).
pubmed: 30085187
pmcid: 6194806
doi: 10.1210/jc.2017-02764
Tata, B. et al. Elevated prenatal anti-Mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nat. Med. 24, 834–846 (2018).
pubmed: 29760445
pmcid: 6098696
doi: 10.1038/s41591-018-0035-5
Maliqueo, M. et al. Placental steroidogenesis in pregnant women with polycystic ovary syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 166, 151–155 (2013).
pubmed: 23122578
doi: 10.1016/j.ejogrb.2012.10.015
Maliqueo, M. et al. Placental STAT3 signaling is activated in women with polycystic ovary syndrome. Hum. Reprod. 30, 692–700 (2015).
pubmed: 25609240
doi: 10.1093/humrep/deu351
Gautam, R., Prambil, A. M., Patel, A. K. & Arora, T. Emerging pollutants in etiology and pathophysiology of polycystic ovary syndrome. Reprod. Toxicol. 123, 108515 (2024).
pubmed: 38000646
doi: 10.1016/j.reprotox.2023.108515
Barker, D. J., Osmond, C. & Law, C. M. The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis. J. Epidemiol. Commun. Health 43, 237–240 (1989).
doi: 10.1136/jech.43.3.237
Barrett, E. S. et al. Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure. J. Dev. Orig. Health Dis. 9, 307–314 (2018).
pubmed: 29310733
pmcid: 5997496
doi: 10.1017/S2040174417001118
Risal, S. et al. Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat. Med. 25, 1894–1904 (2019).
pubmed: 31792459
doi: 10.1038/s41591-019-0666-1
Mimouni, N. E. H. et al. Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process. Cell Metab. 33, 513–530.e8 (2021).
pubmed: 33539777
pmcid: 7928942
doi: 10.1016/j.cmet.2021.01.004
Chen, X., Koivuaho, E., Piltonen, T. T., Gissler, M. & Lavebratt, C. Association of maternal polycystic ovary syndrome or anovulatory infertility with obesity and diabetes in offspring: a population-based cohort study. Hum. Reprod. 36, 2345–2357 (2021).
pubmed: 34046665
pmcid: 8289324
doi: 10.1093/humrep/deab112
Risal, S. et al. Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome. Cell Rep. Med. 4, 101035 (2023).
pubmed: 37148878
pmcid: 10213875
doi: 10.1016/j.xcrm.2023.101035
Lambertini, L. et al. Intrauterine reprogramming of the polycystic ovary syndrome: evidence from a pilot study of cord blood global methylation analysis. Front. Endocrinol. 8, 352 (2017).
doi: 10.3389/fendo.2017.00352
Risal, S. et al. Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders. Transl. Psychiatry 11, 45 (2021).
pubmed: 33441551
pmcid: 7806675
doi: 10.1038/s41398-020-01183-9
Dubey, P. et al. A systematic review and meta-analysis of the association between maternal polycystic ovary syndrome and neuropsychiatric disorders in children. Transl. Psychiatry 11, 569 (2021).
pubmed: 34750348
pmcid: 8575994
doi: 10.1038/s41398-021-01699-8
Stener-Victorin, E. et al. Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome? J. Clin. Endocrinol. Metab. 95, 810–819 (2010).
pubmed: 20016048
doi: 10.1210/jc.2009-1908
Chappell, N. R., Gibbons, W. E. & Blesson, C. S. Pathology of hyperandrogenemia in the oocyte of polycystic ovary syndrome. Steroids 180, 108989 (2022).
pubmed: 35189133
pmcid: 8920773
doi: 10.1016/j.steroids.2022.108989
Gilling-Smith, C., Willis, D. S., Beard, R. W. & Franks, S. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J. Clin. Endocrinol. Metab. 79, 1158–1165 (1994).
pubmed: 7962289
Comim, F. V., Teerds, K., Hardy, K. & Franks, S. Increased protein expression of LHCG receptor and 17α-hydroxylase/17-20-lyase in human polycystic ovaries. Hum. Reprod. 28, 3086–3092 (2013).
pubmed: 24014605
doi: 10.1093/humrep/det352
McAllister, J. M. et al. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc. Natl Acad. Sci. USA 111, E1519–E1527 (2014).
pubmed: 24706793
pmcid: 3992676
doi: 10.1073/pnas.1400574111
Nisenblat, V. & Norman, R. J. Androgens and polycystic ovary syndrome. Curr. Opin. Endocrinol. Diabetes Obes. 16, 224–231 (2009).
pubmed: 19390322
doi: 10.1097/MED.0b013e32832afd4d
Baillargeon, J. P. & Carpentier, A. Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity. Fertil. Steril. 88, 886–893 (2007).
pubmed: 17559844
pmcid: 3846535
doi: 10.1016/j.fertnstert.2006.12.055
di Clemente, N., Racine, C., Pierre, A. & Taieb, J. Anti-mullerian hormone in female reproduction. Endocr. Rev. 42, 753–782 (2021).
pubmed: 33851994
doi: 10.1210/endrev/bnab012
Norman, R. J., Milner, C. R., Groome, N. P. & Robertson, D. M. Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome. Hum. Reprod. 16, 668–672 (2001).
pubmed: 11278215
doi: 10.1093/humrep/16.4.668
Walters, K. A., Allan, C. M. & Handelsman, D. J. Androgen actions and the ovary. Biol. Reprod. 78, 380–389 (2008).
pubmed: 18003945
doi: 10.1095/biolreprod.107.064089
Tropea, A. et al. Estrogens and androgens affect human luteal cell function. Fertil. Steril. 94, 2257–2263 (2010).
pubmed: 20307879
doi: 10.1016/j.fertnstert.2010.02.009
Pea, J. et al. Ultrasonographic criteria in the diagnosis of polycystic ovary syndrome: a systematic review and diagnostic meta-analysis. Hum. Reprod. Update 30, 109–130 (2023).
doi: 10.1093/humupd/dmad027
Wildt, L. et al. Frequency and amplitude of gonadotropin-releasing hormone stimulation and gonadotropin secretion in the rhesus monkey. Endocrinology 109, 376–385 (1981).
pubmed: 6788538
doi: 10.1210/endo-109-2-376
Patel, B. et al. The emerging therapeutic potential of kisspeptin and neurokinin B. Endocr. Rev. 45, 30–68 (2023).
pmcid: 10765167
doi: 10.1210/endrev/bnad023
Koysombat, K., Dhillo, W. S. & Abbara, A. Assessing hypothalamic pituitary gonadal function in reproductive disorders. Clin. Sci. 137, 863–879 (2023).
doi: 10.1042/CS20220146
Burt Solorzano, C. M. et al. Neuroendocrine dysfunction in polycystic ovary syndrome. Steroids 77, 332–337 (2012).
pubmed: 22172593
doi: 10.1016/j.steroids.2011.12.007
Barbotin, A. L. et al. Hypothalamic neuroglial plasticity is regulated by anti-Mullerian hormone and disrupted in polycystic ovary syndrome. EBioMedicine 90, 104535 (2023).
pubmed: 37001236
pmcid: 10070524
doi: 10.1016/j.ebiom.2023.104535
Blank, S. K. et al. Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls–implications for regulation of pubertal maturation. J. Clin. Endocrinol. Metab. 94, 2360–2366 (2009).
pubmed: 19351732
pmcid: 2708962
doi: 10.1210/jc.2008-2606
Palomba, S., Piltonen, T. T. & Giudice, L. C. Endometrial function in women with polycystic ovary syndrome: a comprehensive review. Hum. Reprod. Update 27, 584–618 (2021). This comprehensive review highlights that endometrial dysfunction in PCOS can predispose to miscarriage and pregnancy complications.
pubmed: 33302299
doi: 10.1093/humupd/dmaa051
Wang, A. et al. Expression of GPR30, ERα and ERβ in endometrium during window of implantation in patients with polycystic ovary syndrome: a pilot study. Gynecol. Endocrinol. 27, 251–255 (2011).
pubmed: 21269226
doi: 10.3109/09513590.2010.487584
Apparao, K. B., Lovely, L. P., Gui, Y., Lininger, R. A. & Lessey, B. A. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol. Reprod. 66, 297–304 (2002).
pubmed: 11804942
doi: 10.1095/biolreprod66.2.297
Orostica, L., Poblete, C., Romero, C. & Vega, M. Pro-Inflammatory markers negatively regulate IRS1 in endometrial cells and endometrium from women with obesity and PCOS. Reprod. Sci. 27, 290–300 (2020).
pubmed: 32046436
doi: 10.1007/s43032-019-00026-3
Gibson, D. A., Simitsidellis, I., Collins, F. & Saunders, P. T. K. Androgens, oestrogens and endometrium: a fine balance between perfection and pathology. J. Endocrinol. 246, R75–R93 (2020).
pubmed: 32544881
doi: 10.1530/JOE-20-0106
Piltonen, T. T. et al. Mesenchymal stem/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential. J. Clin. Endocrinol. Metab. 98, 3765–3775 (2013).
pubmed: 23824412
pmcid: 3763978
doi: 10.1210/jc.2013-1923
Piltonen, T. T. et al. Endometrial stromal fibroblasts from women with polycystic ovary syndrome have impaired progesterone-mediated decidualization, aberrant cytokine profiles and promote enhanced immune cell migration in vitro. Hum. Reprod. 30, 1203–1215 (2015).
pubmed: 25750105
pmcid: 4400200
doi: 10.1093/humrep/dev055
Meltsov, A. et al. Targeted gene expression profiling for accurate endometrial receptivity testing. Sci. Rep. 13, 13959 (2023).
pubmed: 37633957
pmcid: 10460380
doi: 10.1038/s41598-023-40991-z
Khatun, M. et al. Decidualized endometrial stromal cells present with altered androgen response in PCOS. Sci. Rep. 11, 16287 (2021).
pubmed: 34381107
pmcid: 8357821
doi: 10.1038/s41598-021-95705-0
Zhou, M. et al. Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization. J. Adv. Res. 30, 15–25 (2021).
pubmed: 34026283
doi: 10.1016/j.jare.2020.09.002
Kangasniemi, M. H. et al. Artificial intelligence deep learning model assessment of leukocyte counts and proliferation in endometrium from women with and without polycystic ovary syndrome. F S Sci. 3, 174–186 (2022).
pubmed: 35560015
Liu, S. et al. Evaluation of endometrial immune status of polycystic ovary syndrome. J. Reprod. Immunol. 144, 103282 (2021).
pubmed: 33607547
doi: 10.1016/j.jri.2021.103282
Ge, X., Zhang, J., Shi, H. & Bu, Z. Polycystic ovary syndrome increases the rate of early spontaneous miscarriage in women who have undergone single vitrified euploid blastocyst transfer. Reprod. Biomed. Online 47, 103223 (2023).
pubmed: 37248146
doi: 10.1016/j.rbmo.2023.04.014
Joshi, A. et al. PCOS and the risk of pre-eclampsia. Reprod. Biomed. Online 45, 961–969 (2022).
pubmed: 35953416
pmcid: 9637709
doi: 10.1016/j.rbmo.2022.05.026
Shetty, C. et al. Risk of gynecological cancers in women with polycystic ovary syndrome and the pathophysiology of association. Cureus 15, e37266 (2023).
pubmed: 37162768
pmcid: 10164440
Zhang, Y. et al. Landscape of PCOS co-expression gene and its role in predicting prognosis and assisting immunotherapy in endometrial cancer. J. Ovarian Res. 16, 129 (2023).
pubmed: 37393293
pmcid: 10315044
doi: 10.1186/s13048-023-01201-6
Dunaif, A., Segal, K. R., Futterweit, W. & Dobrjansky, A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38, 1165–1174 (1989).
pubmed: 2670645
doi: 10.2337/diab.38.9.1165
Dunaif, A. et al. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 41, 1257–1266 (1992).
pubmed: 1397698
doi: 10.2337/diab.41.10.1257
Manneras-Holm, L. et al. Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance. J. Clin. Endocrinol. Metab. 96, E304–E311 (2011). This study demonstrates that enlarged adipocytes together with low adiponectin and increased waist circumference are strong drivers of insulin resistance in women with PCOS.
pubmed: 21084397
doi: 10.1210/jc.2010-1290
Pasquali, R. et al. Insulin and C-peptide levels in obese patients with polycystic ovaries. Horm. Metab. Res. 14, 284–287 (1982).
pubmed: 6749626
doi: 10.1055/s-2007-1018996
Dunaif, A., Xia, J., Book, C. B., Schenker, E. & Tang, Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J. Clin. Invest. 96, 801–810 (1995).
pubmed: 7635975
pmcid: 185266
doi: 10.1172/JCI118126
Caro, J. F., Dohm, L. G., Pories, W. J. & Sinha, M. K. Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab. Rev. 5, 665–689 (1989).
pubmed: 2693017
doi: 10.1002/dmr.5610050804
Corbould, A., Zhao, H., Mirzoeva, S., Aird, F. & Dunaif, A. Enhanced mitogenic signaling in skeletal muscle of women with polycystic ovary syndrome. Diabetes 55, 751–759 (2006).
pubmed: 16505239
doi: 10.2337/diabetes.55.03.06.db05-0453
Skov, V. et al. Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome. Diabetes 56, 2349–2355 (2007).
pubmed: 17563058
doi: 10.2337/db07-0275
Nilsson, E. et al. Transcriptional and epigenetic changes influencing skeletal muscle metabolism in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 103, 4465–4477 (2018).
pubmed: 30113663
doi: 10.1210/jc.2018-00935
Stepto, N. K. et al. Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis. Endocr. Connect. 9, 346–359 (2020).
pubmed: 32229703
pmcid: 7219141
doi: 10.1530/EC-19-0551
Manti, M., Stener-Victorin, E. & Benrick, A. Skeletal muscle immunometabolism in women with polycystic ovary syndrome: a meta-analysis. Front. Physiol. 11, 573505 (2020).
pubmed: 33192572
pmcid: 7642984
doi: 10.3389/fphys.2020.573505
Stener-Victorin, E. et al. Proteomic analysis shows decreased type I fibers and ectopic fat accumulation in skeletal muscle from women with PCOS. eLife 12, e87592 (2024). This study showed that PCOS leads to a shift in muscle fibre type resulting in fewer insulin-sensitive type 1 muscle fibres and an increased accumulation of fat in skeletal muscles.
doi: 10.7554/eLife.87592
Barber, T. M. et al. Global adiposity rather than abnormal regional fat distribution characterizes women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 999–1004 (2008).
pubmed: 18089693
doi: 10.1210/jc.2007-2117
Tchernof, A. et al. Androgens and the regulation of adiposity and body fat distribution in humans. Compr. Physiol. 8, 1253–1290 (2018).
pubmed: 30215860
doi: 10.1002/cphy.c170009
Raeisi, T. et al. Circulating resistin and follistatin levels in obese and non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis. PLoS ONE 16, e0246200 (2021).
pubmed: 33740002
pmcid: 7978365
doi: 10.1371/journal.pone.0246200
Schuler-Toprak, S., Ortmann, O., Buechler, C. & Treeck, O. The complex roles of adipokines in polycystic ovary syndrome and endometriosis. Biomedicines 10, 2503 (2022).
pubmed: 36289764
pmcid: 9598769
doi: 10.3390/biomedicines10102503
Echiburu, B. et al. Enlarged adipocytes in subcutaneous adipose tissue associated to hyperandrogenism and visceral adipose tissue volume in women with polycystic ovary syndrome. Steroids 130, 15–21 (2018).
pubmed: 29273198
doi: 10.1016/j.steroids.2017.12.009
Chazenbalk, G. et al. Androgens inhibit adipogenesis during human adipose stem cell commitment to preadipocyte formation. Steroids 78, 920–926 (2013).
pubmed: 23707571
pmcid: 3951890
doi: 10.1016/j.steroids.2013.05.001
Blouin, K. et al. Effects of androgens on adipocyte differentiation and adipose tissue explant metabolism in men and women. Clin. Endocrinol. 72, 176–188 (2010).
doi: 10.1111/j.1365-2265.2009.03645.x
Fisch, S. C. et al. Precocious subcutaneous abdominal stem cell development to adipocytes in normal-weight women with polycystic ovary syndrome. Fertil. Steril. 110, 1367–1376 (2018).
pubmed: 30503136
pmcid: 6287278
doi: 10.1016/j.fertnstert.2018.08.042
Dumesic, D. A. et al. Accelerated subcutaneous abdominal stem cell adipogenesis predicts insulin sensitivity in normal-weight women with polycystic ovary syndrome. Fertil. Steril. 116, 232–242 (2021).
pubmed: 33341231
doi: 10.1016/j.fertnstert.2020.10.003
Ezeh, U., Chen, I. Y., Chen, Y. H. & Azziz, R. Adipocyte expression of glucose transporter 1 and 4 in PCOS: relationship to insulin-mediated and non-insulin-mediated whole-body glucose uptake. Clin. Endocrinol. 90, 542–552 (2019).
doi: 10.1111/cen.13931
Ezeh, U., Chen, I. Y., Chen, Y. H. & Azziz, R. Adipocyte insulin resistance in PCOS: relationship with GLUT-4 expression and whole-body glucose disposal and β-cell function. J. Clin. Endocrinol. Metab. 105, e2408-20 (2020).
doi: 10.1210/clinem/dgaa235
Faulds, G., Ryden, M., Ek, I., Wahrenberg, H. & Arner, P. Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 88, 2269–2273 (2003).
pubmed: 12727985
doi: 10.1210/jc.2002-021573
Arner, P. Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome. Biochimie 87, 39–43 (2005).
pubmed: 15733735
doi: 10.1016/j.biochi.2004.11.012
Ek, I. et al. A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes 51, 484–492 (2002).
pubmed: 11812759
doi: 10.2337/diabetes.51.2.484
Morigny, P., Boucher, J., Arner, P. & Langin, D. Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics. Nat. Rev. Endocrinol. 17, 276–295 (2021).
pubmed: 33627836
doi: 10.1038/s41574-021-00471-8
Ek, I., Arner, P., Bergqvist, A., Carlstrom, K. & Wahrenberg, H. Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J. Clin. Endocrinol. Metab. 82, 1147–1153 (1997).
pubmed: 9100587
Bril, F. et al. Adipose tissue dysfunction in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 109, 10–24 (2023).
pubmed: 37329216
doi: 10.1210/clinem/dgad356
Chazenbalk, G. et al. Regulation of adiponectin secretion by adipocytes in the polycystic ovary syndrome: role of tumor necrosis factor-α. J. Clin. Endocrinol. Metab. 95, 935–942 (2010).
pubmed: 20089616
pmcid: 2840865
doi: 10.1210/jc.2009-1158
O’Reilly, M. W. et al. AKR1C3-mediated adipose androgen generation drives lipotoxicity in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 102, 3327–3339 (2017). This study demonstrates that adipose tissue in PCOS has intra-adipose androgen activation contributing to adipose tissue remodelling with lipid accumulation and insulin resistance.
pubmed: 28645211
pmcid: 5587066
doi: 10.1210/jc.2017-00947
Huang, Z. H. et al. PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity. J. Clin. Endocrinol. Metab. 98, E17–24 (2013).
pubmed: 23118428
doi: 10.1210/jc.2012-2697
Chazenbalk, G. et al. Abnormal expression of genes involved in inflammation, lipid metabolism, and Wnt signaling in the adipose tissue of polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 97, E765–E770 (2012).
pubmed: 22344199
pmcid: 3339894
doi: 10.1210/jc.2011-2377
Jones, M. R. et al. Systems genetics reveals the functional context of PCOS loci and identifies genetic and molecular mechanisms of disease heterogeneity. PLoS Genet. 11, e1005455 (2015).
pubmed: 26305227
pmcid: 4549292
doi: 10.1371/journal.pgen.1005455
Kokosar, M. et al. Epigenetic and transcriptional alterations in human adipose tissue of polycystic ovary syndrome. Sci. Rep. 6, e1022883 (2016).
Velez, L. M., Seldin, M. & Motta, A. B. Inflammation and reproductive function in women with polycystic ovary syndrome. Biol. Reprod. 104, 1205–1217 (2021).
pubmed: 33739372
pmcid: 8785941
doi: 10.1093/biolre/ioab050
Wu, Z. et al. Association of circulating monocyte chemoattractant protein-1 levels with polycystic ovary syndrome: a meta-analysis. Am. J. Reprod. Immunol. 86, e13407 (2021).
pubmed: 33638245
doi: 10.1111/aji.13407
Vasyukova, E. et al. Inflammatory and anti-inflammatory parameters in PCOS patients depending on body mass index: a case-control study. Biomedicines 11, 2791 (2023).
pubmed: 37893164
pmcid: 10604137
doi: 10.3390/biomedicines11102791
Aboeldalyl, S. et al. The role of chronic inflammation in polycystic ovarian syndrome-a systematic review and meta-analysis. Int. J. Mol. Sci. 22, 2734 (2021).
pubmed: 33800490
pmcid: 7962967
doi: 10.3390/ijms22052734
He, S. et al. Peripheral blood inflammatory-immune cells as a predictor of infertility in women with polycystic ovary syndrome. J. Inflamm. Res. 13, 441–450 (2020).
pubmed: 32884325
pmcid: 7443446
doi: 10.2147/JIR.S260770
Juan, C. C. et al. Increased regulated on activation, normal T-cell expressed and secreted levels and cysteine-cysteine chemokine receptor 5 upregulation in omental adipose tissue and peripheral blood mononuclear cells are associated with testosterone level and insulin resistance in polycystic ovary syndrome. Fertil. Steril. 116, 1139–1146 (2021).
pubmed: 34119324
doi: 10.1016/j.fertnstert.2021.05.093
Kem, D. C. et al. The role of GnRH receptor autoantibodies in polycystic ovary syndrome. J. Endocr. Soc. 4, bvaa078 (2020).
pubmed: 32803090
pmcid: 7417878
doi: 10.1210/jendso/bvaa078
Xiao, N. et al. Altered subsets and activities of B lymphocytes in polycystic ovary syndrome. J. Allergy Clin. Immunol. 143, 1943–1945.e4 (2019).
pubmed: 30677479
doi: 10.1016/j.jaci.2019.01.007
Ascani, A. et al. The role of B cells in immune cell activation in polycystic ovary syndrome. eLife 12, e86454 (2023). Although this study highlights that B cells are affected in PCOS, potentially contributing to an increased susceptibility to certain comorbidities, the findings suggest that B cells do not themselves cause PCOS.
pubmed: 37401759
pmcid: 10359092
doi: 10.7554/eLife.86454
Yildirim, E. et al. Echocardiographic evaluation of diastolic functions in patients with polycystic ovary syndrome: a comperative study of diastolic functions in sub-phenotypes of polycystic ovary syndrome. Cardiol. J. 24, 364–373 (2017).
pubmed: 28353313
doi: 10.5603/CJ.a2017.0032
Berbrier, D. E. et al. Effects of androgen excess and body mass index on endothelial function in women with polycystic ovary syndrome. J. Appl. Physiol. 134, 868–878 (2023).
pubmed: 36861670
doi: 10.1152/japplphysiol.00583.2022
Talbott, E. O. et al. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 89, 5454–5461 (2004).
pubmed: 15531497
doi: 10.1210/jc.2003-032237
Lakhani, K., Hardiman, P. & Seifalian, A. M. Intima-media thickness of elastic and muscular arteries of young women with polycystic ovaries. Atherosclerosis 175, 353–359 (2004).
pubmed: 15262192
doi: 10.1016/j.atherosclerosis.2004.04.007
Manneras-Holm, L. et al. Coagulation and fibrinolytic disturbances in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 96, 1068–1076 (2011).
pubmed: 21252248
doi: 10.1210/jc.2010-2279
Shoemaker, J. K., Klassen, S. A., Badrov, M. B. & Fadel, P. J. Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans. J. Neurophysiol. 119, 1731–1744 (2018).
pubmed: 29412776
pmcid: 6008088
doi: 10.1152/jn.00841.2017
Lambert, E. A. et al. Sympathetic activation and endothelial dysfunction in polycystic ovary syndrome are not explained by either obesity or insulin resistance. Clin. Endocrinol. 83, 812–819 (2015).
doi: 10.1111/cen.12803
Shorakae, S. et al. Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS. Clin. Endocrinol. 89, 628–633 (2018).
doi: 10.1111/cen.13808
Sverrisdottir, Y. B., Mogren, T., Kataoka, J., Janson, P. O. & Stener-Victorin, E. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am. J. Physiol. Endocrinol. Metab. 294, E576–E581 (2008). This study was the first to demonstrate that women with PCOS have increased muscle sympathetic nerve activity with testosterone and cholesterol as independent predictors for the elevated activity, which may contribute to the increased cardiovascular risk in the syndrome.
pubmed: 18198350
doi: 10.1152/ajpendo.00725.2007
Manneras, L., Cajander, S., Lonn, M. & Stener-Victorin, E. Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R1124–1131 (2009).
pubmed: 19158405
doi: 10.1152/ajpregu.90947.2008
Stener-Victorin, E., Jedel, E., Janson, P. O. & Sverrisdottir, Y. B. Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R387–395 (2009).
pubmed: 19494176
doi: 10.1152/ajpregu.00197.2009
Ely, B. R. et al. Heat therapy reduces sympathetic activity and improves cardiovascular risk profile in women who are obese with polycystic ovary syndrome. Am. J. Physiol. Regul. Integr. Comp. Physiol. 317, R630–R640 (2019).
pubmed: 31483156
pmcid: 8424543
doi: 10.1152/ajpregu.00078.2019
Mahfoud, F. et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation 123, 1940–1946 (2011).
pubmed: 21518978
doi: 10.1161/CIRCULATIONAHA.110.991869
Schlaich, M. P. et al. Renal denervation: a potential new treatment modality for polycystic ovary syndrome? J. Hypertens. 29, 991–996 (2011).
pubmed: 21358414
doi: 10.1097/HJH.0b013e328344db3a
Young, C. N., Deo, S. H., Chaudhary, K., Thyfault, J. P. & Fadel, P. J. Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans. J. Physiol. 588, 3593–3603 (2010).
pubmed: 20643774
pmcid: 2988520
doi: 10.1113/jphysiol.2010.191866
Ketel, I. J. et al. Greater arterial stiffness in polycystic ovary syndrome (PCOS) is an obesity–but not a PCOS-associated phenomenon. J. Clin. Endocrinol. Metab. 95, 4566–4575 (2010).
pubmed: 20660051
doi: 10.1210/jc.2010-0868
Ollila, M. M. et al. Effect of polycystic ovary syndrome on cardiac autonomic function at a late fertile age: a prospective Northern Finland Birth Cohort 1966 study. BMJ Open 9, e033780 (2019).
pubmed: 31843853
pmcid: 6924836
doi: 10.1136/bmjopen-2019-033780
Philbois, S. V. et al. Women with polycystic ovarian syndrome exhibit reduced baroreflex sensitivity that may be associated with increased body fat. Arq. Bras. Cardiol. 112, 424–429 (2019).
pubmed: 30843930
pmcid: 6459434
Qu, X. & Donnelly, R. Sex hormone-binding globulin (SHBG) as an early biomarker and therapeutic target in polycystic ovary syndrome. Int. J. Mol. Sci. 21, 8191 (2020).
pubmed: 33139661
pmcid: 7663738
doi: 10.3390/ijms21218191
Rock, K. L., Latz, E., Ontiveros, F. & Kono, H. The sterile inflammatory response. Annu. Rev. Immunol. 28, 321–342 (2010).
pubmed: 20307211
pmcid: 4315152
doi: 10.1146/annurev-immunol-030409-101311
Polderman, T. J. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702–709 (2015).
pubmed: 25985137
doi: 10.1038/ng.3285
Jiang, X., Deng, Q. & Stener-Victorin, E. Is there a shared genetic basis and causal relationship between polycystic ovary syndrome and psychiatric disorders: evidence from a comprehensive genetic analysis. Hum. Reprod. 36, 2382–2391 (2021).
pubmed: 34051085
doi: 10.1093/humrep/deab119
Hu, M. et al. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring. Proc. Natl Acad. Sci. USA 112, 14348–14353 (2015).
pubmed: 26578781
pmcid: 4655563
doi: 10.1073/pnas.1507514112
Manti, M. et al. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring. FASEB J. 32, 4158–4171 (2018).
pubmed: 29565738
doi: 10.1096/fj.201701263RR
Fitzgerald, E., Hor, K. & Drake, A. J. Maternal influences on fetal brain development: the role of nutrition, infection and stress, and the potential for intergenerational consequences. Early Hum. Dev. 150, 105190 (2020).
pubmed: 32948364
pmcid: 7481314
doi: 10.1016/j.earlhumdev.2020.105190
Palm, C. V. B. et al. Prenatal androgen exposure and traits of autism spectrum disorder in the offspring: Odense child cohort. J. Autism Dev. Disord. 53, 1053–1065 (2023).
pubmed: 35124780
doi: 10.1007/s10803-022-05446-w
Dalgaard, C. M. et al. Maternal polycystic ovary syndrome and attention deficit hyperactivity disorder in offspring at 3 years of age: Odense child cohort. Acta Obstet. Gynecol. Scand. 100, 2053–2065 (2021).
pubmed: 34490610
doi: 10.1111/aogs.14259
Chen, X., Kong, L., Piltonen, T. T., Gissler, M. & Lavebratt, C. Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study. Hum. Reprod. 35, 2336–2347 (2020).
pubmed: 32866965
pmcid: 7518708
doi: 10.1093/humrep/deaa192
Robinson, S. L. et al. The associations of maternal polycystic ovary syndrome and hirsutism with behavioral problems in offspring. Fertil. Steril. 113, 435–443 (2020).
pubmed: 32106995
pmcid: 7185046
doi: 10.1016/j.fertnstert.2019.09.034
Tian, X. et al. Sexual function in Chinese women with different clinical phenotypes of polycystic ovary syndrome. Gynecol. Endocrinol. 39, 2221736 (2023).
pubmed: 37302412
doi: 10.1080/09513590.2023.2221736
Mojahed, B. S., Ghajarzadeh, M., Khammar, R. & Shahraki, Z. Depression, sexual function and sexual quality of life in women with polycystic ovary syndrome (PCOS) and healthy subjects. J. Ovarian Res. 16, 105 (2023).
pubmed: 37254195
pmcid: 10228014
doi: 10.1186/s13048-023-01171-9
Noroozzadeh, M., Ramezani Tehrani, F., Bahri Khomami, M. & Azizi, F. A comparison of sexual function in women with polycystic ovary syndrome (PCOS) whose mothers had PCOS during their pregnancy period with those without PCOS. Arch. Sex. Behav. 46, 2033–2042 (2017).
pubmed: 28070801
doi: 10.1007/s10508-016-0919-8
Silva, M. S. B. et al. Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway. Proc. Natl Acad. Sci. USA 119, e2203503119 (2022).
pubmed: 35867816
pmcid: 9335209
doi: 10.1073/pnas.2203503119
Joham, A. E. et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 10, 668–680 (2022).
pubmed: 35934017
doi: 10.1016/S2213-8587(22)00163-2
Teede, H. J. et al. Recommendations from the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Fertil. Steril. 110, 364–379 (2018).
pubmed: 30033227
pmcid: 6939856
doi: 10.1016/j.fertnstert.2018.05.004
Pena, A. S. et al. Adolescent polycystic ovary syndrome according to the international evidence-based guideline. BMC Med. 18, 72 (2020).
pubmed: 32204714
pmcid: 7092491
doi: 10.1186/s12916-020-01516-x
Tay, C. T. et al. Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood. BMC Med. 18, 389 (2020).
pubmed: 33302955
pmcid: 7731536
doi: 10.1186/s12916-020-01861-x
Dong, J. & Rees, D. A. Polycystic ovary syndrome: pathophysiology and therapeutic opportunities. BMJ Med. 2, e000548 (2023).
pubmed: 37859784
pmcid: 10583117
doi: 10.1136/bmjmed-2023-000548
Urakami, T. Maturity-onset diabetes of the young (MODY): current perspectives on diagnosis and treatment. Diabetes Metab. Syndr. Obes. 12, 1047–1056 (2019).
pubmed: 31360071
pmcid: 6625604
doi: 10.2147/DMSO.S179793
Kataoka, J. et al. Weight management interventions in women with and without PCOS: a systematic review. Nutrients 9, 996 (2017).
pubmed: 28885578
pmcid: 5622756
doi: 10.3390/nu9090996
Lim, S. S. et al. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst. Rev. 3, CD007506 (2019).
pubmed: 30921477
Moran, L. J. et al. C-reactive protein before and after weight loss in overweight women with and without polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92, 2944–2951 (2007).
pubmed: 17504892
doi: 10.1210/jc.2006-2336
American Diabetes Association Professional Practice Committee. 3. Prevention or delay of type 2 diabetes and associated comorbidities: standards of medical care in diabetes-2022. Diabetes Care 45, S39–S45 (2022).
doi: 10.2337/dc22-S003
Chiavaroli, L. et al. DASH dietary pattern and cardiometabolic outcomes: an umbrella review of systematic reviews and meta-analyses. Nutrients 11, 338 (2019).
pubmed: 30764511
pmcid: 6413235
doi: 10.3390/nu11020338
Ge, L. et al. Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials. BMJ 369, m696 (2020).
pubmed: 32238384
pmcid: 7190064
doi: 10.1136/bmj.m696
Papadaki, A., Nolen-Doerr, E. & Mantzoros, C. S. The effect of the Mediterranean diet on metabolic health: a systematic review and meta-analysis of controlled trials in adults. Nutrients 12, 3342 (2020).
pubmed: 33143083
pmcid: 7692768
doi: 10.3390/nu12113342
Sievenpiper, J. L. Low-carbohydrate diets and cardiometabolic health: the importance of carbohydrate quality over quantity. Nutr. Rev. 78, 69–77 (2020).
pubmed: 32728757
pmcid: 7390653
doi: 10.1093/nutrit/nuz082
Benham, J. L. et al. Exercise training and reproductive outcomes in women with polycystic ovary syndrome: a pilot randomized controlled trial. Clin. Endocrinol. 95, 332–343 (2021).
doi: 10.1111/cen.14452
Ribeiro, V. B. et al. Effects of continuous and intermittent aerobic physical training on hormonal and metabolic profile, and body composition in women with polycystic ovary syndrome: a randomized controlled trial. Clin. Endocrinol. 93, 173–186 (2020).
doi: 10.1111/cen.14194
Carlsson, L. M. S. et al. Life expectancy after bariatric surgery in the Swedish obese subjects study. N. Engl. J. Med. 383, 1535–1543 (2020).
pubmed: 33053284
pmcid: 7580786
doi: 10.1056/NEJMoa2002449
Eisenberg, D. et al. 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): indications for metabolic and bariatric surgery. Surg. Obes. Relat. Dis. 18, 1345–1356 (2022).
pubmed: 36280539
doi: 10.1016/j.soard.2022.08.013
Hu, L. et al. Efficacy of bariatric surgery in the treatment of women with obesity and polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 107, e3217–e3229 (2022).
pubmed: 35554540
pmcid: 9282367
doi: 10.1210/clinem/dgac294
Tatarchuk, T. et al. The effect of gastric sleeve resection on menstrual pattern and ovulation in premenopausal women with classes III-IV obesity. Obes. Surg. 32, 599–606 (2022).
pubmed: 34817794
doi: 10.1007/s11695-021-05820-0
Melin, J. et al. The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Eur. J. Endocrinol. 189, S37–S63 (2023).
pubmed: 37536294
doi: 10.1093/ejendo/lvad098
Ge, J. J., Wang, D. J., Song, W., Shen, S. M. & Ge, W. H. The effectiveness and safety of liraglutide in treating overweight/obese patients with polycystic ovary syndrome: a meta-analysis. J. Endocrinol. Invest. 45, 261–273 (2022).
pubmed: 34455568
doi: 10.1007/s40618-021-01666-6
Teede, H. et al. Effect of the combined oral contraceptive pill and/or metformin in the management of polycystic ovary syndrome: a systematic review with meta-analyses. Clin. Endocrinol. 91, 479–489 (2019).
doi: 10.1111/cen.14013
Elkind-Hirsch, K. E., Chappell, N., Shaler, D., Storment, J. & Bellanger, D. Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study. Fertil. Steril. 118, 371–381 (2022). This study showed that GLP1 analogue is superior to placebo in reducing body weight and hyperandrogenism as well as improving cardiometabolic variables in women with PCOS.
pubmed: 35710599
doi: 10.1016/j.fertnstert.2022.04.027
Carmina, E. & Longo, R. A. Semaglutide treatment of excessive body weight in obese PCOS patients unresponsive to lifestyle programs. J. Clin. Med. 12, 5921 (2023).
pubmed: 37762862
pmcid: 10531549
doi: 10.3390/jcm12185921
Fonseka, S. et al. Effectiveness of low-dose ethinylestradiol/cyproterone acetate and ethinylestradiol/desogestrel with and without metformin on hirsutism in polycystic ovary syndrome: a randomized, double-blind, triple-dummy study. J. Clin. Aesthet. Dermatol. 13, 18–23 (2020).
pubmed: 32983332
pmcid: 7492016
Forslund, M. et al. Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis. Eur. J. Endocrinol. 189, S1–S16 (2023).
pubmed: 37440702
doi: 10.1093/ejendo/lvad082
Melin, J. et al. Metformin and combined oral contraceptive pills in the management of polycystic ovary syndrome: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 109, e817–e836 (2023).
pmcid: 10795934
doi: 10.1210/clinem/dgad465
Bhandari, M. et al. Effects of bariatric surgery on people with obesity and polycystic ovary syndrome: a large single center study from India. Obes. Surg. 32, 3305–3312 (2022).
pubmed: 35882755
doi: 10.1007/s11695-022-06209-3
Lullo, J. J. et al. Incidence of androgenic dermatologic side effects following placement of a levonorgestrel intrauterine device for menorrhagia: a survey-based study. J. Am. Acad. Dermatol. 79, 364–365 (2018).
pubmed: 29288103
doi: 10.1016/j.jaad.2017.12.051
King, L., Gajarawala, S. & McCrary, M. D. Endometrial cancer and obesity: addressing the awkward silence. JAAPA 36, 28–31 (2023).
pubmed: 36573814
doi: 10.1097/01.JAA.0000902884.01725.a3
Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil. Steril. 89, 505–522 (2008).
doi: 10.1016/j.fertnstert.2007.09.041
Benito, E. et al. Fertility and pregnancy outcomes in women with polycystic ovary syndrome following bariatric surgery. J. Clin. Endocrinol. Metab. 105, dgaa439 (2020).
pubmed: 32754732
doi: 10.1210/clinem/dgaa439
Legro, R. S. et al. Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 100, 4048–4058 (2015).
pubmed: 26401593
pmcid: 4702450
doi: 10.1210/jc.2015-2778
Boomsma, C. M. et al. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum. Reprod. Update 12, 673–683 (2006).
pubmed: 16891296
doi: 10.1093/humupd/dml036
de Wilde, M. A. et al. Increased rates of complications in singleton pregnancies of women previously diagnosed with polycystic ovary syndrome predominantly in the hyperandrogenic phenotype. Fertil. Steril. 108, 333–340 (2017).
pubmed: 28778282
doi: 10.1016/j.fertnstert.2017.06.015
Wang, R. et al. First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis. Hum. Reprod. Update 25, 717–732 (2019).
pubmed: 31647106
doi: 10.1093/humupd/dmz029
Wang, R. Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. BMJ 356, j138 (2017); erratum 379, o2436 (2022).
Legro, R. S. et al. Letrozole or clomiphene for infertility in the polycystic ovary syndrome. N. Engl. J. Med. 371, 1463–1464 (2014).
pubmed: 25295506
doi: 10.1056/NEJMoa1313517
Pundir, J. et al. Risk of foetal harm with letrozole use in fertility treatment: a systematic review and meta-analysis. Hum. Reprod. Update 27, 474–485 (2021).
pubmed: 33374012
doi: 10.1093/humupd/dmaa055
Bordewijk, E. M. et al. Long-term outcomes of switching to gonadotrophins versus continuing with clomiphene citrate, with or without intrauterine insemination, in women with normogonadotropic anovulation and clomiphene failure: follow-up study of a factorial randomized clinical trial. Hum. Reprod. 38, 421–429 (2023).
pubmed: 36622200
pmcid: 9977112
doi: 10.1093/humrep/deac268
Chen, Z. J. et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N. Engl. J. Med. 375, 523–533 (2016).
pubmed: 27509101
doi: 10.1056/NEJMoa1513873
Chen, N. et al. Risk factors associated with monozygotic twinning in offspring conceived by assisted reproductive technology. Hum. Reprod. Open 2023, hoad035 (2023).
pubmed: 37840637
pmcid: 10570986
doi: 10.1093/hropen/hoad035
Zhang, B. et al. Obstetric complications after frozen versus fresh embryo transfer in women with polycystic ovary syndrome: results from a randomized trial. Fertil. Steril. 109, 324–329 (2018).
pubmed: 29338857
doi: 10.1016/j.fertnstert.2017.10.020
Magnusson, A. et al. Endometrial preparation protocols prior to frozen embryo transfer — convenience or safety? Reprod. Biomed. Online 48, 103587 (2023).
pubmed: 37949762
doi: 10.1016/j.rbmo.2023.103587
Gilchrist, R. B. et al. A fresh start for IVM: capacitating the oocyte for development using pre-IVM. Hum. Reprod. Update 30, 3–25 (2023).
doi: 10.1093/humupd/dmad023
Pham, H. H. et al. Cumulative live birth rate after oocyte in vitro maturation with a pre-maturation step in women with polycystic ovary syndrome or high antral follicle count. J. Assist. Reprod. Genet. 40, 827–835 (2023).
pubmed: 36821006
pmcid: 10224896
doi: 10.1007/s10815-023-02752-9
Stein, I. F. Multiple pregnancy following wedge resection in the Stein-Leventhal syndrome. Int. J. Fertil. 9, 343–350 (1964).
pubmed: 14145796
Nahuis, M. J. et al. Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation. Hum. Reprod. 27, 3577–3582 (2012).
pubmed: 23001778
doi: 10.1093/humrep/des336
Bayram, N., van Wely, M., Kaaijk, E. M., Bossuyt, P. M. & van der Veen, F. Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial. BMJ 328, 192 (2004).
pubmed: 14739186
pmcid: 318481
doi: 10.1136/bmj.328.7433.192
Baradwan, S. et al. Transvaginal needle versus laparoscopic ovarian drilling in hormonal profile and pregnancy outcomes of polycystic ovary syndrome: a systematic review and meta-analysis. J. Gynecol. Obstet. Hum. Reprod. 52, 102606 (2023).
pubmed: 37207714
doi: 10.1016/j.jogoh.2023.102606
Dokras, A. et al. Weight loss and lowering androgens predict improvements in health-related quality of life in women with PCOS. J. Clin. Endocrinol. Metab. 101, 2966–2974 (2016). Weight loss and oral contraceptives improve HRQoL as well as depressive and anxiety symptoms and when combined they offer further benefits in women with overweight and obesity and PCOS.
pubmed: 27253669
pmcid: 4971336
doi: 10.1210/jc.2016-1896
Jiskoot, G. et al. Long-term effects of a three-component lifestyle intervention on emotional well-being in women with polycystic ovary syndrome (PCOS): a secondary analysis of a randomized controlled trial. PLoS ONE 15, e0233876 (2020).
pubmed: 32479544
pmcid: 7263605
doi: 10.1371/journal.pone.0233876
Cooney, L. G. et al. Cognitive-behavioral therapy improves weight loss and quality of life in women with polycystic ovary syndrome: a pilot randomized clinical trial. Fertil. Steril. 110, 161–171 e161 (2018).
pubmed: 29908771
pmcid: 6443091
doi: 10.1016/j.fertnstert.2018.03.028
Melson, E. et al. A systematic review of models of care for polycystic ovary syndrome highlights the gap in the literature, especially in developing countries. Front. Endocrinol. 14, 1217468 (2023).
doi: 10.3389/fendo.2023.1217468
Behboodi Moghadam, Z., Fereidooni, B., Saffari, M. & Montazeri, A. Measures of health-related quality of life in PCOS women: a systematic review. Int. J. Womens Health 10, 397–408 (2018).
pubmed: 30123008
pmcid: 6078086
doi: 10.2147/IJWH.S165794
Karjula, S. et al. Population-based data at ages 31 and 46 show decreased HRQoL and life satisfaction in women with PCOS symptoms. J. Clin. Endocrinol. Metab. 105, 1814–1826 (2020).
pubmed: 31970392
pmcid: 7150615
doi: 10.1210/clinem/dgz256
Cronin, L. et al. Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS). J. Clin. Endocrinol. Metab. 83, 1976–1987 (1998).
pubmed: 9626128
Guyatt, G., Weaver, B., Cronin, L., Dooley, J. A. & Azziz, R. Health-related quality of life in women with polycystic ovary syndrome, a self-administered questionnaire, was validated. J. Clin. Epidemiol. 57, 1279–1287 (2004).
pubmed: 15617954
doi: 10.1016/j.jclinepi.2003.10.018
Williams, S., Sheffield, D. & Knibb, R. C. The polycystic ovary syndrome quality of life scale (PCOSQOL): development and preliminary validation. Health Psychol. Open 5, 2055102918788195 (2018).
pubmed: 30038788
pmcid: 6053872
doi: 10.1177/2055102918788195
Saei Ghare Naz, M. et al. Adolescents’ polycystic ovary syndrome health-related quality of life questionnaire (APQ-20): development and psychometric properties. Eur. J. Pediatr. 182, 2393–2407 (2023).
pubmed: 36907946
doi: 10.1007/s00431-023-04875-8
Azziz, R. et al. Recommendations for epidemiologic and phenotypic research in polycystic ovary syndrome: an androgen excess and PCOS society resource. Hum. Reprod. 34, 2254–2265 (2019).
pubmed: 31751476
doi: 10.1093/humrep/dez185
Al Wattar, B. H. et al. Harmonising research outcomes for polycystic ovary syndrome: an international multi-stakeholder core outcome set. Hum. Reprod. 35, 404–412 (2020).
pubmed: 32020203
doi: 10.1093/humrep/dez272
Kiconco, S. et al. PCOS phenotype in unselected populations study (P-PUP): protocol for a systematic review and defining PCOS diagnostic features with pooled individual participant data. Diagnostics 11, 1953 (2021).
pubmed: 34829300
pmcid: 8618006
doi: 10.3390/diagnostics11111953
Gibson-Helm, M., Dokras, A., Karro, H., Piltonen, T. & Teede, H. J. Knowledge and practices regarding polycystic ovary syndrome among physicians in Europe, North America, and internationally: an online questionnaire-based study. Semin. Reprod. Med. 36, 19–27 (2018).
pubmed: 30189447
doi: 10.1055/s-0038-1667155
Schünemann, H., Brożek, J., Guyatt, G. & Oxman, A. (eds) GRADE Handbook (GRADE Working Group, 2013).
James, D. E., Stockli, J. & Birnbaum, M. J. The aetiology and molecular landscape of insulin resistance. Nat. Rev. Mol. Cell Biol. 22, 751–771 (2021).
pubmed: 34285405
doi: 10.1038/s41580-021-00390-6
Di Guardo, F., Ciotta, L., Monteleone, M. & Palumbo, M. Male equivalent polycystic ovarian syndrome: hormonal, metabolic, and clinical aspects. Int. J. Fertil. Steril. 14, 79–83 (2020).
pubmed: 32681618
pmcid: 7382675
Lunde, O., Magnus, P., Sandvik, L. & Hoglo, S. Familial clustering in the polycystic ovarian syndrome. Gynecol. Obstet. Invest. 28, 23–30 (1989).
pubmed: 2777131
doi: 10.1159/000293493
Sanke, S., Chander, R., Jain, A., Garg, T. & Yadav, P. A comparison of the hormonal profile of early androgenetic alopecia in men with the phenotypic equivalent of polycystic ovarian syndrome in women. JAMA Dermatol. 152, 986–991 (2016).
pubmed: 27304785
doi: 10.1001/jamadermatol.2016.1776
Starka, L., Duskova, M., Cermakova, I., Vrbikova, J. & Hill, M. Premature androgenic alopecia and insulin resistance. Male equivalent of polycystic ovary syndrome? Endocr. Regul. 39, 127–131 (2005).
pubmed: 16552990
Crisosto, N. et al. Reproductive and metabolic features during puberty in sons of women with polycystic ovary syndrome. Endocr. Connect. 6, 607–613 (2017). This study further supports that not only daughters but also sons of women with PCOS present with metabolic and minor reproductive dysfunctions.
pubmed: 28912339
pmcid: 5640572
doi: 10.1530/EC-17-0218
Liu, D. M. et al. Evidence for gonadotrophin secretory and steroidogenic abnormalities in brothers of women with polycystic ovary syndrome. Hum. Reprod. 29, 2764–2772 (2014).
pubmed: 25336708
pmcid: 4227582
doi: 10.1093/humrep/deu282
Torchen, L. C. et al. Increased antimullerian hormone levels and other reproductive endocrine changes in adult male relatives of women with polycystic ovary syndrome. Fertil. Steril. 106, 50–55 (2016).
pubmed: 27042970
pmcid: 4930891
doi: 10.1016/j.fertnstert.2016.03.029
Baillargeon, J. P. & Carpentier, A. C. Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects. Diabetologia 50, 2424–2432 (2007).
pubmed: 17898989
pmcid: 3846531
doi: 10.1007/s00125-007-0831-9
Sam, S., Coviello, A. D., Sung, Y. A., Legro, R. S. & Dunaif, A. Metabolic phenotype in the brothers of women with polycystic ovary syndrome. Diabetes Care 31, 1237–1241 (2008).
pubmed: 18332151
doi: 10.2337/dc07-2190
Sam, S., Sung, Y. A., Legro, R. S. & Dunaif, A. Evidence for pancreatic β-cell dysfunction in brothers of women with polycystic ovary syndrome. Metabolism 57, 84–89 (2008).
pubmed: 18078863
pmcid: 2710887
doi: 10.1016/j.metabol.2007.08.010
Karthik, S. et al. Cardiovascular disease risk in the siblings of women with polycystic ovary syndrome. Hum. Reprod. 34, 1559–1566 (2019).
pubmed: 31299073
doi: 10.1093/humrep/dez104
Subramaniam, K., Tripathi, A. & Dabadghao, P. Familial clustering of metabolic phenotype in brothers of women with polycystic ovary syndrome. Gynecol. Endocrinol. 35, 601–603 (2019).
pubmed: 30727783
doi: 10.1080/09513590.2019.1566451
Joham, A. E., Boyle, J. A., Ranasinha, S., Zoungas, S. & Teede, H. J. Contraception use and pregnancy outcomes in women with polycystic ovary syndrome: data from the Australian Longitudinal Study on Women’s Health. Hum. Reprod. 29, 802–808 (2014).
pubmed: 24549213
doi: 10.1093/humrep/deu020
Dokras, A. et al. Androgen excess- polycystic ovary syndrome society: position statement on depression, anxiety, quality of life, and eating disorders in polycystic ovary syndrome. Fertil. Steril. 109, 888–899 (2018).
pubmed: 29778388
doi: 10.1016/j.fertnstert.2018.01.038