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Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis
Abstract
BACKGROUND: Conflicting results regarding adiponectin levels in women with polycystic ovary syndrome (PCOS) have been reported. To evaluate adiponectin levels in PCOS, a systematic review of all studies comparing adiponectin levels in women with PCOS with healthy controls and a meta-analysis of those involving women with similar body mass index (BMI) were performed. The influence of possible effect modifiers, such as insulin resistance (IR) and testosterone, was investigated. The influence of obesity was investigated through a 'nested' meta-analysis after within-study BMI stratification and appropriate pooling. METHODS: Literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL (through June 2008), references from relevant studies and personal contact with the authors. Thirty-one studies, reporting data on 3469 subjects, were reviewed and 16 included in the main meta-analysis. RESULTS: Women with PCOS demonstrated significantly lower adiponectin values [weighted mean difference (95% confidence interval) -1.71 (-2.82 to -0.6), P < 10(-4)], yet with significant between-study heterogeneity. Lower adiponectin levels are associated with the IR observed in women with PCOS, compared with controls. IR, but not total testosterone, was found significant among biological parameters explored in the meta-regression model. Hypoadiponectinaemia was present in both lean and obese women with PCOS when compared with non-PCOS counterparts. Data on high molecular weight (HMW) adiponectin are limited (three studies). CONCLUSIONS: After controlling for BMI-related effects, adiponectin levels seem to be lower in women with PCOS compared with non-PCOS controls. Low levels of adiponectin in PCOS are probably related to IR but not to testosterone. Total adiponectin should not be used as a biomarker of PCOS severity. Further investigation is needed for HMW adiponectin levels in PCOS.
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“after controlling for BMI-related effects, adiponectin levels appear to be lower in women with PCOS than in controls without PCOS [44].”
From PCOS and nutritional approaches: Differences between lean and obese phenotype (2021) · cites this paper as [44]
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Adipocyte biology in polycystic ovary syndrome
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“…that following adjustment for BMI-related effects, serum levels of adiponectin are indeed lower in women with PCOS compared with control women, and that low levels of adiponectin in PCOS are likely to be related to the insulin resistance associated with this condition (Toulis et al., 2009).”
BackgroundImmunological and Metabolic Causes of Infertility in Polycystic Ovary Syndrome
Kicińska, A. M., Maksym, R., Zabielska-Kaczorowska, M. A., Stachowska, A., & Babińska, A. (2023) · Biomedicines · doi:10.3390/biomedicines11061567 · Cited by 108
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Vryonidou, A., Paschou, S. A., Muscogiuri, G., Orio, F., & Goulis, D. G. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0275 · Cited by 88
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“When PCOS and non-PCOS NAFLD groups were compared, no difference in the levels of resistin, adiponectin and insulin were observed, thus, confirming the findings of others [29,30] and pointing to the fact that the levels of these hormones are defined by underlying metabolic states and patient’s BMI, rather than by PCOS.”
ResultThe use of metformin in women with polycystic ovary syndrome: an updated review
Notaro, A. L. G., & Neto, F. T. L. (2022) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-022-02429-9 · Cited by 83
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Paris, V. R., Solon‐Biet, S. M., Senior, A. M., Edwards, M. C., Desai, R., Tedla, N. T., Cox, M. J., Ledger, W. J., Gilchrist, R. B., Simpson, S. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19003-5 · Cited by 86
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“Ameta-analysis has demonstrated that adiponectin levels are lower in PCOS women than in control women of comparable BMI [98].”
BackgroundAdiponectin and the Control of Female Reproductive Functions
Palin, M., Bordignon, V., & Murphy, B. D. (2012) · Vitamins and hormones · doi:10.1016/b978-0-12-398313-8.00010-5 · Cited by 83
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“Adiponectin tends to be lower in women with anovulatory PCOS compared with weight-matched controls or women with ovulatory PCOS (Carmina et al., 2009; Toulis et al., 2009).”
BackgroundSex-gender-related therapeutic approaches for cardiovascular complications associated with diabetes
Campesi, I., Franconi, F., Seghieri, G., & Meloni, M. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.01.023 · Cited by 80
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ResultLuque‐Ramírez, M., Martínez-García, M. Á., Montes‐Nieto, R., Fernández‐Durán, E., Insenser, M. R., Alpañés, M., & Escobar-Morreale, H. F. (2013) · Human Reproduction · doi:10.1093/humrep/det097 · Cited by 73
“Furthermore, hyperandrogenic women present with hypoadiponectinemia irrespective of weight excess (Toulis et al., 2009) and the amelioration of androgen excess by using an antiandrogenic contraceptive pill increases serum adiponectin levels in obese patients with androgen excess (Luque-Ramı́rez et al.”
BackgroundWang, D., Zhu, W., Jie-ming, L., An, C., & Wang, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081190 · Cited by 73
“Moreover, according to one meta-analysis [39], adiponectin levels were lower in PCOS women compared with healthy control subjects of a similar BMI.”
Abasian, Z., Rostamzadeh, A., Mohammadi, M., Hosseini, M., & Rafieian‐Kopaei, M. (2018) · Middle East Fertility Society Journal · doi:10.1016/j.mefs.2018.04.005 · Cited by 72
Metabolic hormones are integral regulators of female reproductive health and function
Athar, F., Karmani, M., & Templeman, N. M. (2023) · Bioscience Reports · doi:10.1042/bsr20231916 · Cited by 82
“Women with PCOS also have significantly lower adiponectin levels that correlate with lower metabolic health, compared with individuals matched for body mass index [586,587].”
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Adipose expression of adipocytokines in women with polycystic ovary syndrome
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“The role of plasma adiponectin levels in the pathophysiology of PCOS is controversial, but a meta-analysis has suggested that there are lower circulating levels of adiponectin in women with PCOS (9).”
BackgroundChazenbalk, G. D., Trivax, B., Yıldız, B. O., Bertolotto, C., Mathur, R., Heneidi, S. G., & Azziz, R. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1158 · Cited by 66
“significant heterogeneity across individual studies (32).”
Sarray, S., Madan, S., Saleh, L. R., Mahmoud, N., & Almawi, W. Y. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.05.007 · Cited by 62
Androgen signaling pathways driving reproductive and metabolic phenotypes in a PCOS mouse model
Aflatounian, A., Edwards, M. C., Paris, V. R., Bertoldo, M. J., Desai, R., Gilchrist, R. B., Ledger, W. J., Handelsman, D. J., & Walters, K. A. (2020) · Journal of Endocrinology · doi:10.1530/joe-19-0530 · Cited by 61
Testosterone a key factor in gender related metabolic syndrome
Bianchi, V. E., & Locatelli, V. (2018) · Obesity Reviews · doi:10.1111/obr.12633 · Cited by 65
“In PCOS women, adiponectin level is lower compared with non-PCOS women, and it seems more correlated with body fat mass rather that androgens level (84).”
BackgroundDokras, A. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.10.027 · Cited by 60
Implications of adiponectin in linking metabolism to testicular function
Martin, L. J. (2013) · Endocrine · doi:10.1007/s12020-013-0102-0 · Cited by 60
Cloix, L., Reverchon, M., Cornuau, M., Froment, P., Ramé, C., Costa, C., Froment, G., Lecomte, P., Chen, W., Royère, D., et al. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.114.120410 · Cited by 59
“A metaanalysis revealed that serum ADIPOQ levels are lower in women with PCOS than in BMI-matched healthy controls [25].”
BackgroundLow Circulating Adiponectin Levels in Women with Polycystic Ovary Syndrome: An Updated Meta-Analysis
Li, S., Huang, X., Zhong, H., Peng, Q., Chen, S., Xie, Y., Qin, X., & Qin, A. (2014) · Tumor Biology · doi:10.1007/s13277-013-1595-0 · Cited by 58
“[24] published a meta-analysis comparing circulating adiponectin levels in women with PCOS and non-PCOS controls matched for similar body mass index (BMI).”
BackgroundAssociation between circulating adiponectin levels and polycystic ovarian syndrome
Mirza, S. S., Shafique, K., Shaikh, A. R., Khan, N. A., & Qureshi, M. A. (2014) · Journal of Ovarian Research · doi:10.1186/1757-2215-7-18 · Cited by 58
“Clinical features of PCOS namely hirsutism, acne, and alopecia originate from high circulating levels of androgens, menstrual irregularities from anovulatory cycles [2], and obesity is thought to originate from both the underlying IR [1] and high androgen levels in these patients [3].”
BackgroundResultThe roles of leptin and adiponectin at the fetal-maternal interface in humans
Dos Santos, E., Duval, F., Vialard, F., & Dieudonné, M.-N. (2015) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2015-0031 · Cited by 52
Sun, Y., Li, S., Liu, H., Bai, H., Hu, K., Zhang, R., Liu, Q., & Fan, P. (2021) · Fertility and Sterility · doi:10.1016/j.fertnstert.2021.07.1203 · Cited by 52
Obesity and Polycystic Ovary Syndrome
Kim, J. (2024) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes24035 · Cited by 53
“69 Additionally, diminished adiponectin levels could lead to hyperandro-genemia as adiponectin inhibits sex steroid production by thecal cells.”
Kominiarek, M. A., Jungheim, E. S., Hoeger, K. M., Rogers, A. M., Kahan, S. I., & Kim, J. J. (2017) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2017.02.006 · Cited by 50
“Lower adiponectin levels are associated with IR observed in women with PCOS compared with controls [27].”
BackgroundBehboudi‐Gandevani, S., Tehrani, F. R., Yarandi, R. B., Noroozzadeh, M., Hedayati, M., & Azizi, F. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0650-x · Cited by 49
Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise
Covington, J. D., Tam, C. S., Pasarica, M., & Redman, L. M. (2014) · Biochimie · doi:10.1016/j.biochi.2014.10.028 · Cited by 48
“with PCOS have been conflicting, with some showing lower levels and others showing no differences [44-46].”
BackgroundPolycystic ovary syndrome and its management: In view of oxidative stress
Bhattacharya, K., Dey, R., Sen, D., Paul, N., Basak, A. K., Purkait, M. P., Shukla, N., Chaudhuri, G. R., Bhattacharya, A., Maiti, R., et al. (2024) · BioMolecular Concepts · doi:10.1515/bmc-2022-0038 · Cited by 52
“FSH impact on GCs regulates these conversion processes [28,29].”
BackgroundBaldani, D. P., Škrgatić, L., Kasum, M., Zlopaša, G., Oguić, S. K., & Herman, M. (2019) · Gynecological Endocrinology · doi:10.1080/09513590.2018.1534096 · Cited by 46
“Several reports have described associations of adiponectin levels with indicators of IR [17–19] which were further supported by a meta-analysis published in 2009 [17].”
ResultChoi, Y. S., Yang, H. I., Cho, S., Jung, J. A., Jeon, Y. E., Kim, H. Y., Seo, S. K., & Lee, B. S. (2012) · Steroids · doi:10.1016/j.steroids.2012.08.005 · Cited by 46
Mannerås-Holm, L., Benrick, A., & Stener‐Victorin, E. (2014) · Adipocyte · doi:10.4161/adip.28731 · Cited by 43
Polycystic Ovary Syndrome: Impact of Lipotoxicity on Metabolic and Reproductive Health
Brennan, K. M., Kroener, L. L., Chazenbalk, G. D., & Dumesic, D. A. (2019) · Obstetrical & Gynecological Survey · doi:10.1097/ogx.0000000000000661 · Cited by 44
Yan, S., Ding, J., Zhang, Y., Wang, J., Zhang, S., Yin, T., & Yang, J. (2021) · Biology of Reproduction · doi:10.1093/biolre/ioab094 · Cited by 43
Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome
Sadeghi, A., Fadaei, R., Moradi, N., Fouani, F. Z., Roozbehkia, M., Zandieh, Z., Ansaripour, S., Vatannejad, A., & Doustimotlagh, A. H. (2020) · IUBMB Life · doi:10.1002/iub.2272 · Cited by 41
Raeisi, T., Rezaie, H., Darand, M., Taheri, A., Garousi, N., Razi, B., Roever, L., Mohseni, R., Mohammed, S. H., & Alizadeh, S. (2021) · PLoS ONE · doi:10.1371/journal.pone.0246200 · Cited by 41
“Recently, there has been an increasing interest in exploring the changes in circulating adipokines in PCOS patients; meta-analysis of changes in many important adipokines in context of PCOS such as omentin-1 [18], leptin [19, 20], interleukin-6(IL-6) [21], visfatin [22], tumor necrosis factor-alpha (TNF-a) [23], adipo…”
BackgroundPCOS in Adolescence and Type 2 Diabetes
Carreau, A.-M., & Baillargeon, J.-P. (2015) · Current Diabetes Reports · doi:10.1007/s11892-014-0564-3 · Cited by 40
Mehrabani, S., Arab, A., Karimi, E., Nouri, M., & Mansourian, M. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00709-w · Cited by 40
“Moreover, the possible role of these adipokines in the etiopathology of PCOS has been also suggested [13, 14].”
Backgroundde Resende, L. O. T., Vireque, A. A., Santana, L. F., Moreno, D. A., Silva, A. C. J. D. S. R. E., Ferriani, R. A., Scrideli, C. A., & dos Reis, R. M. (2012) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-012-9825-8 · Cited by 39
“This syndrome presents defects in primary cellular control mechanisms that result in the expression of chronic anovulation, hyperandrogenism, and polycystic ovaries [2, 3].”
BackgroundFactors determining the risk of the metabolic syndrome: is there a central role for adiponectin?
Calton, E. K., Miller, V. S., & Soares, M. J. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.1 · Cited by 39
Uyanıkoğlu, H., Sabuncu, T., Dursun, H., Sezen, H., & Aksoy, N. (2016) · Biomarkers · doi:10.1080/1354750x.2016.1265004 · Cited by 38
Rondanelli, M., Perna, S., Faliva, M. A., Monteferrario, F., Repaci, E., & Allieri, F. (2014) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-014-3433-z · Cited by 44
“meta-analysis [69] revealed that serum adiponectin levels are lower in women with PCOS compared with BMI-”
Result
Metadata
- Authors
- Toulis, K. A., Goulis, D. G., Farmakiotis, D., Georgopoulos, N. A., Katsikis, I., Tarlatzis, B. C., Papadimas, I., & Panidis, D.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- University of Patras (GR)
- Venue
- Human Reproduction Update
- Publisher
- Oxford University Press (OUP)
- Published
- 2009
- Volume
- 15
- Issue
- 3
- Pages
- 297-307
- ISSN
- 1355-4786 (ISSN-L)
- 1460-2369
- OpenAlex
- W2131241159
- Cited by
- 262
- References
- 72
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 14 · 2021: 20 · 2020: 19 · 2019: 13 · 2018: 12 · 2017: 17 · 2016: 10 · 2015: 21 · 2014: 17 · 2013: 23 · 2012: 25
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction Update (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Warwick
- University of Adelaide
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- polycystic ovary syndrome, adiponectin, insulin resistance, testosterone, obesity, body mass index, high molecular weight adiponectin
- MeSH terms
- Female, Humans, Insulin Resistance, Obesity, Polycystic Ovary Syndrome, Regression Analysis, Testosterone, Adiponectin
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