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DOI: 10.1055/a-1463-3198
The Impact of Subclinical Hypothyroidism on Patients with Polycystic Ovary Syndrome: A Meta-Analysis
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Abstract
The association between subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) has been shown in many studies. These findings are still controversial, however. It is unclear whether the co-incidence of subclinical hypothyroidism and polycystic ovary syndrome will affect the severity of metabolism. Therefore, we performed this meta-analysis to investigate the association. A comprehensive search strategy was developed to obtain all relevant studies published in PubMed, EMBASE, Cochrane Library, and Chinese Academic Journal Full-text Database (CNKI) up to 31 December 2020. We adopted the standardized mean difference (SMD) with 95% confidence intervals (CI) for evaluation, and sensitivity analysis was performed. Publication bias was analyzed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger’s test. Twenty-seven studies with 4821 participants (1300 PCOS patients with SCH, 3521 PCOS patients without SCH) were included in the present meta-analysis,among which 71.31% chinese patients out of the total. The results showed that PCOS patients with SCH had higher levels of HOMA-IR, TG, TC, LDL, FBG, FCP, PRL and lower levels of HDL, LH and T. It also recognized the limitation of the lack of a consistent definition of hypothyroidism in the 27 studies included. The results of this study indicated that SCH may aggravate lipid and glucose metabolism in patients with PCOS.
Publication History
Received: 05 March 2021
Accepted after revision: 11 March 2021
Article published online:
21 June 2021
© 2021. Thieme. All rights reserved.
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References
- 1 March WA, Moore VM, Willson KJ. et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod (Oxford, England) 2010; 25: 544-551
- 2 Devru N, Dharmshaktu P, Kumar G. et al. Phenotypic presentation of adolescents with overt primary hypothyroidism. J Pediatr Endocrinol Metab 2018; 31: 415-420
- 3 Dumesic DA, Oberfield SE, Stener-Victorin E. et al. Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome. Endocr Rev 2015; 36: 487-525
- 4 Surks MI, Ortiz E, Daniels GH. et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291: 228-238
- 5 Cooper DS. Clinical practice. Subclinical hypothyroidism. N Engl J Med 2001; 345: 260-265
- 6 Ganie MA, Laway BA, Wani TA. et al. Association of subclinical hypothyroidism and phenotype, insulin resistance, and lipid parameters in young women with polycystic ovary syndrome. Fertil Steril 2011; 95: 2039-2043
- 7 Du D, Li X. The relationship between thyroiditis and polycystic ovary syndrome: a meta-analysis. Int J Clin Exp Med 2013; 6: 880-889
- 8 Rotondi M, Cappelli C, Magri F. et al. Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2011; 75: 378-381
- 9 Muderris II, Boztosun A, Oner G. et al. Effect of thyroid hormone replacement therapy on ovarian volume and androgen hormones in patients with untreated primary hypothyroidism. Ann Saudi Med 2011; 31: 145-151
- 10 Celik C, Abali R, Tasdemir N. et al. Is subclinical hypothyroidism contributing dyslipidemia and insulin resistance in women with polycystic ovary syndrome?. Gynecol Endocrinol 2012; 28: 615-618
- 11 Benetti-Pinto CL, Berini Piccolo VRS. et al. Subclinical hypothyroidism in young women with polycystic ovary syndrome: An analysis of clinical, hormonal, and metabolic parameters. Fertil Steril 2013; 99: 588-592
- 12 Yu Q, Wang JB. Subclinical hypothyroidism in PCOS: Impact on presentation, insulin resistance, and cardiovascular risk. BioMed Res Int. 2016 2067087.
- 13 Pei YJ, Wang AM, Zhao Y. et al. Studies of cardiovascular risk factors in polycystic ovary syndrome patients combined with subclinical hypothyroidism. Gynecol Endocrinol 2014; 30: 553-556
- 14 Lu YH, Xia ZL, Ma YY. et al. Subclinical hypothyroidism is associated with metabolic syndrome and clomiphene citrate resistance in women with polycystic ovary syndrome. Gynecol Endocrinol 2016; 32: 852-855
- 15 Enzevaei A, Salehpour S, Tohidi M. et al. Subclinical hypothyroidism and insulin resistance in polycystic ovary syndrome: Is there a relationship?. Iran J Reprod Med 2014; 12: 481-486
- 16 Trakakis E, Pergialiotis V, Hatziagelaki E. et al. Subclinical hypothyroidism does not influence the metabolic and hormonal profile of women with PCOS. Horm Mol Biol. Clin Invest 2017; 31 (03) DOI: 10.1515/hmbci-2016-0058.
- 17 Bedaiwy MA, Abdel-Rahman MY, Tan J. et al. Clinical, Hormonal, and Metabolic Parameters in Women with Subclinical Hypothyroidism and Polycystic Ovary Syndrome: A Cross-Sectional Study. J Wom Health (2002) 2018; 27: 659-664
- 18 de-Medeiros SF, Yamamoto MMW, de-Medeiros MAS. et al. Should Subclinical Hypothyroidism Be an Exclusion Criterion for the Diagnosis of Polycystic Ovary Syndrome?. J Reprod Infertil 2017; 18: 242-250
- 19 Yanni X, Yi W, Ruixin M. Study on the difference of endocrine and metabolic indexes in patients with polycystic ovary syndrome with or without subclinical hypothyroidism. Chin J Endocrinol Metab 2014; 30: 187-191
- 20 Haiying C. Thyroxine in the Treatment of Polycystic Ovary Syndrome with Subclinical Hypothyroidism. Master. Nanhua University. 2013
- 21 Wenhui G. Study on the relationship between polycystic ovary syndrome and subclinical hypothyroidism. Master. Jilin University. 2017
- 22 Yan J. Analysis of the correlation between subclinical hypothyroidism and polycystic ovary syndrome. Chin J Wom Child Health 2019; 10: 61-63
- 23 Lifeng L, Xiaoxiao H, Ruohan W. et al. The therapeutic effect of levothyroxine on ovulation disorders and metabolic abnormalities in patients with polycystic ovary syndrome and subclinical hypothyroidism. Chin J Gen Pract 2017; 15: 1856-1859
- 24 Youjuan P, Aiming W, Yong Z. et al. The study of insulin levels and blood lipid changes in patients with polycystic ovary syndrome and subclinical hypothyroidism. J Reprod Med 2013; 22: 285-290
- 25 Shibin D. Study on the difference of endocrine and metabolism indicators in patients with polycystic ovary syndrome with or without subclinical hypothyroidism. Int Med Health Guid News 2015; 21: 9
- 26 Jing W, Haixiang S, Yan B. et al. The relationship between subclinical hypothyroidism and body composition and insulin resistance in overweight and obese patients with polycystic ovary syndrome,Chinese Journal of Clin Nutr 2017; 25: 366-371
- 27 Dongmei Y, Xiangyan R, Xuanxuan T. et al. The effect of subclinical hypothyroidism on insulin resistance and lipid metabolism in patients with polycystic ovary syndrome. Chin Med Herald 2018; 15: 68-71
- 28 Junrong Z. The Effect of Subclinical Hypothyroidism on the Metabolism of Polycystic Ovary Syndrome. Master Zhengzhou University. 2018
- 29 Xiaoping Z, Jianing Z, Haizhen Y. et al. Changes in hormone and glycolipid levels in patients with POCS and subclinical hypothyroidism. J Shanxi Med Uni 2015; 46: 920-923
- 30 Fangzhi Y, Dongmei Z, Fei G. et al. The relationship between subclinical hypothyroidism and endocrine and metabolism characteristics in patients with polycystic ovary syndrome. J Central South Univ (Medical Science) 2017; 42: 940-946
- 31 Xiong P, Xiuyi H, Aizhong C. To explore the interaction between polycystic ovary syndrome and subclinical hypothyroidism. J Hunan Norm University (Medical Sciences) 2018; 15: 174-177
- 32 Rong H, Jun Z, Shengxian L. et al. Subclinical hypothyroidism in patients with polycystic ovary syndrome: distribution and its association with lipid profiles. Pubmed. 2014 177.
- 33 Na Y, Xin L. A study on the correlation between subclinical hypothyroidism and metabolic abnormalities in PCOS patients. Chin Mod Doctor 2019; 57: 30-33 38
- 34 Dittrich R, Kajaia N, Cupisti S. et al. Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS. Reprod Biomed Online 2009; 19: 319-325
- 35 Ying Z, Xiaoping K, Lichun N. et al. Study on the correlation between subclinical hypothyroidism and abnormal glucose and lipid metabolism in patients with polycystic ovary syndrome. Shaanxi Med J 2015; 44: 662-663 666
- 36 Ding X, Yang L, Wang J. et al. Subclinical hypothyroidism in polycystic ovary syndrome: A Systematic review and meta-analysis. Front Endocrinol 2018; 9: 700.39
- 37 Garelli S, Masiero S, Plebani M. et al. High prevalence of chronic thyroiditis in patients with polycystic ovary syndrome. Eur J Obstetr Gynecol Reprod Biol 2013; 169: 248-251
- 38 Effraimidis G, Wiersinga WM. Mechanisms in endocrinology: Autoimmune thyroid disease: old and new players. Eur J Endocrinol 2014; 170: R241-R252
- 39 Mutinati M, Desantis S, Rizzo A. et al. Localization of thyrotropin receptor and thyroglobulin in the bovine corpus luteum. Anim Reprod Sci 2010; 118: 1-6
- 40 Bagavandoss P, England B, Asirvatham A. et al. Transient induction of polycystic ovary-like syndrome in immature hypothyroid rats. Proceedings of the Society for Experimental Biology and Medicine Society for Experimental Biol Med (New York, NY) 1998; 219: 77-84
- 41 Morteza TS, Rokni H, Fatemi S. Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism. Diabetes Vascul Dis Res 2011; 8: 47-48
- 42 Krysiak R, Okopien B. The effect of metformin on the hypothalamic-pituitary-thyroid axis in women with polycystic ovary syndrome and subclinical hypothyroidism. J Clin Pharmacol 2015; 55: 45-49
- 43 Rizos CV, Elisaf MS, Liberopoulos EN. et al. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J 2011; 5: 76-84
- 44 Gullberg H, Rudling M, Saltó C. et al. Requirement for thyroid hormone receptor beta in T3 regulation of cholesterol metabolism in mice. Mol Endocrinol (Baltimore. Md) 2002; 16: 1767-1777
- 45 Chang YC, Hua SC, Chang CH. et al. High TSH Level within Normal Range Is Associated with Obesity, Dyslipidemia, Hypertension, Inflammation, Hypercoagulability, and the Metabolic Syndrome: A Novel Cardiometabolic Marker. J Clin Med 2019; 8: 817
- 46 Zhou L, Ding S, Li Y. et al. Endoplasmic Reticulum stress may play a pivotal role in lipid metabolic disorders in a novel mouse model of subclinical hypothyroidism. Sci Rep 2016; 6: 31381
- 47 Bakker SJ, ter Maaten JC, Popp-Snijders C. et al. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab 2001; 86: 1206-1211
- 48 Ness GC, Chambers CM. Feedback and hormonal regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase: the concept of cholesterol buffering capacity. Proc Soc Exp Biol Med (New York, NY) 2000; 224: 8-19
- 49 Michalopoulou G, Alevizaki M, Piperingos G. et al. High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?. Eur J Endocrinol 1998; 138: 141-145
- 50 Guzel S, Seven A, Guzel EC. et al. Visfatin, Leptin, and TNF-α: Interrelated Adipokines in Insulin-Resistant Clinical and Subclinical Hypothyroidism. Endocr Res 2013; 38: 184-194
- 51 Koritschoner NP, Alvarez-Dolado M, Kurz SM. et al. Thyroid hormone regulates the obesity gene tub. EMBO Rep 2001; 2: 499-504
- 52 Dimitriadis G, Mitrou P, Lambadiari V. et al. Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab 2006; 91: 4930-4937
- 53 Maratou E, Hadjidakis DJ, Kollias A. et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol 2009; 160: 785-790
- 54 Mullur R, Liu YY, Brent GA. et al. Thyroid hormone regulation of metabolism. Physiol Rev 2014; 94: 355-382
- 55 Torrance CJ, Devente JE, Jones JP. et al. Effects of thyroid hormone on GLUT4 glucose transporter gene expression and NIDDM in rats. Endocrinology 1997; 138: 1204-1214
- 56 Xu C, Zhou L, Wu K. et al. Abnormal Glucose Metabolism and Insulin Resistance Are Induced via the IRE1α/XBP-1 Pathway in Subclinical Hypothyroidism. Front Endocrinol 2019; 10: 303
- 57 Tuzcu A, Bahceci M, Gokalp D. et al. Subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr J 2005; 52: 89-94
- 58 Reis FM, Reis AM, Coimbra CC. et al. Effects of hyperprolactinaemia on glucose tolerance and insulin release in male and female rats. J Endocrinol 1997; 153: 423-428
- 59 Bauer DC, Ettinger B, Browner WS. et al. Thyroid functions and serum lipids in older women: A population-based study. Am J Med 1998; 104: 546-551