胰岛素抵抗对多囊卵巢综合征生殖内分泌及代谢的影响

doi:10.12280/gjfckx.20230032

摘要/Abstract

摘要：

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是育龄期妇女最常见的内分泌功能障碍性疾病，具有多种生殖和代谢表型。其中约50%~70%的PCOS患者合并胰岛素抵抗（insulin resistance，IR）。IR在PCOS的发生及发展过程中起着重要作用，其不仅影响PCOS患者的生殖内分泌功能，还可增加PCOS患者代谢紊乱的发生风险。IR与高雄激素血症相互影响，共同推动PCOS的发展。IR与月经紊乱程度相关，PCOS患者子宫内膜局部的IR可降低子宫内膜容受性。IR加剧PCOS患者脂代谢紊乱，推动非酒精性脂肪性肝病的发生和发展。IR影响脂肪组织的发育和功能，肥胖亦影响机体对胰岛素的敏感性。IR还可减少骨形成，阻碍骨吸收，增加骨质疏松的发生风险，对PCOS患者骨代谢产生不利影响。对以上方面进行阐述，以期为改善PCOS伴IR患者的代谢紊乱及生殖功能提供参考。

关键词: 多囊卵巢综合征, 多囊卵巢综合征, 胰岛素抵抗, 胰岛素抵抗, 雄激素类, 雄激素类, 月经周期, 月经周期, 子宫内膜, 子宫内膜, 脂代谢障碍, 脂代谢障碍, 骨和骨组织, 骨和骨组织

Abstract:

Polycystic ovary syndrome (PCOS) represents the most common disease with endocrine dysfunctional in women of reproductive age with multiple reproductive and metabolic phenotypes. About 50%-70% of the PCOS patients have combined insulin resistance (IR). IR plays a significant role in the occurrence and development of PCOS. Not only does IR affect the reproductive endocrine function of PCOS patients, but also increases the risk of metabolic disorders in PCOS patients. IR and hyperandrogenism interact with each other to promote the development of PCOS. IR is associated with the degree of menstrual disorder. IR in partial endometrium of PCOS patients decreases endometrial receptivity. IR aggravates PCOS patients′ disorder of lipid metabolism，promoting the occurrence and development of non-alcoholic fatty liver disease. IR affects the development and function of adipose tissue. Obesity also affects insulin sensitivity. IR can reduce bone formation, hinder bone resorption, and aggravate the risk of osteoporosis, and adversely affects bone metabolism in patients with PCOS. This article elaborating from the above aspects, is expected to provide reference for improving the metabolic disorder and reproductive function of PCOS patients with IR.

Key words: Polycystic ovary syndrome, Polycystic ovary syndrome, Insulin resistance, Insulin resistance, Androgens, Androgens, Menstrual cycle, Menstrual cycle, Endometrium, Endometrium, Lipid metabolism disorders, Lipid metabolism disorders, Bone and bones, Bone and bones

刘音, 鲁娣, 宋殿荣. 胰岛素抵抗对多囊卵巢综合征生殖内分泌及代谢的影响[J]. 国际妇产科学杂志, 2023, 50(2): 190-195.

LIU Yin, LU Di, SONG Dian-rong. The Effect of Insulin Resistance on Reproductive Endocrine and Metabolism of Polycystic Ovary Syndrome[J]. Journal of International Obstetrics and Gynecology, 2023, 50(2): 190-195.

参考文献 44

[1]	Joham AE, Norman RJ, Stener-Victorin E, et al. Polycystic ovary syndrome[J]. Lancet Diabetes Endocrinol, 2022, 10(9):668-680. doi: 10.1016/S2213-8587(22)00163-2. doi: 10.1016/S2213-8587(22)00163-2
	Joham AE, Norman RJ, Stener-Victorin E, et al. Polycystic ovary syndrome[J]. Lancet Diabetes Endocrinol, 2022, 10(9):668-680. doi: 10.1016/S2213-8587(22)00163-2. doi: 10.1016/S2213-8587(22)00163-2
[2]	乔杰, 李蓉, 李莉, 等. 多囊卵巢综合征——多囊卵巢综合征流行病学研究[J]. 中国实用妇科与产科杂志, 2013, 29(11):849-852.
	乔杰, 李蓉, 李莉, 等. 多囊卵巢综合征——多囊卵巢综合征流行病学研究[J]. 中国实用妇科与产科杂志, 2013, 29(11):849-852.
[3]	Pani A, Gironi I, Di Vieste G, et al. From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management[J]. Int J Endocrinol, 2020, 2020:6276187. doi: 10.1155/2020/6276187. doi: 10.1155/2020/6276187
	Pani A, Gironi I, Di Vieste G, et al. From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management[J]. Int J Endocrinol, 2020, 2020:6276187. doi: 10.1155/2020/6276187. doi: 10.1155/2020/6276187
[4]	Pérez-López FR, Ornat L, López-Baena MT, et al. Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression[J]. Eur J Obstet Gynecol Reprod Biol, 2021, 260:85-98. doi: 10.1016/j.ejogrb.2021.03.007. doi: 10.1016/j.ejogrb.2021.03.007 pmid: 33744505
	Pérez-López FR, Ornat L, López-Baena MT, et al. Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression[J]. Eur J Obstet Gynecol Reprod Biol, 2021, 260:85-98. doi: 10.1016/j.ejogrb.2021.03.007. doi: 10.1016/j.ejogrb.2021.03.007 pmid: 33744505
[5]	Cassar S, Misso ML, Hopkins WG, et al. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies[J]. Hum Reprod, 2016, 31(11):2619-2631. doi: 10.1093/humrep/dew243. doi: 10.1093/humrep/dew243
	Cassar S, Misso ML, Hopkins WG, et al. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies[J]. Hum Reprod, 2016, 31(11):2619-2631. doi: 10.1093/humrep/dew243. doi: 10.1093/humrep/dew243
[6]	Maffazioli G, Lopes CP, Heinrich-Oliveira V, et al. Prevalence of metabolic disturbances among women with polycystic ovary syndrome in different regions of Brazil[J]. Int J Gynaecol Obstet, 2020, 151(3):383-391. doi: 10.1002/ijgo.13374. doi: 10.1002/ijgo.13374
	Maffazioli G, Lopes CP, Heinrich-Oliveira V, et al. Prevalence of metabolic disturbances among women with polycystic ovary syndrome in different regions of Brazil[J]. Int J Gynaecol Obstet, 2020, 151(3):383-391. doi: 10.1002/ijgo.13374. doi: 10.1002/ijgo.13374
[7]	Kim JJ, Hwang KR, Oh SH, et al. Prevalence of insulin resistance in Korean women with polycystic ovary syndrome according to various homeostasis model assessment for insulin resistance cutoff values[J]. Fertil Steril, 2019, 112(5):959-966.e1. doi: 10.1016/j.fertnstert.2019.06.035. doi: S0015-0282(19)30575-8 pmid: 31542165
	Kim JJ, Hwang KR, Oh SH, et al. Prevalence of insulin resistance in Korean women with polycystic ovary syndrome according to various homeostasis model assessment for insulin resistance cutoff values[J]. Fertil Steril, 2019, 112(5):959-966.e1. doi: 10.1016/j.fertnstert.2019.06.035. doi: S0015-0282(19)30575-8 pmid: 31542165
[8]	Zippl AL, Seeber B, Wildt L. Insulin resistance: still an underestimated factor in polycystic ovary syndrome?[J]. Fertil Steril, 2021, 115(6):1447-1448. doi: 10.1016/j.fertnstert.2021.03.020. doi: 10.1016/j.fertnstert.2021.03.020 pmid: 33863552
	Zippl AL, Seeber B, Wildt L. Insulin resistance: still an underestimated factor in polycystic ovary syndrome?[J]. Fertil Steril, 2021, 115(6):1447-1448. doi: 10.1016/j.fertnstert.2021.03.020. doi: 10.1016/j.fertnstert.2021.03.020 pmid: 33863552
[9]	Belenkaia LV, Lazareva LM, Walker W, et al. Criteria, phenotypes and prevalence of polycystic ovary syndrome[J]. Minerva Ginecol, 2019, 71(3):211-223. doi: 10.23736/S0026-4784.19.04404-6. doi: 10.23736/S0026-4784.19.04404-6 pmid: 31089072
	Belenkaia LV, Lazareva LM, Walker W, et al. Criteria, phenotypes and prevalence of polycystic ovary syndrome[J]. Minerva Ginecol, 2019, 71(3):211-223. doi: 10.23736/S0026-4784.19.04404-6. doi: 10.23736/S0026-4784.19.04404-6 pmid: 31089072
[10]	Huang-Doran I, Kinzer AB, Jimenez-Linan M, et al. Ovarian Hyperandrogenism and Response to Gonadotropin-releasing Hormone Analogues in Primary Severe Insulin Resistance[J]. J Clin Endocrinol Metab, 2021, 106(8):2367-2383. doi: 10.1210/clinem/dgab275. doi: 10.1210/clinem/dgab275
	Huang-Doran I, Kinzer AB, Jimenez-Linan M, et al. Ovarian Hyperandrogenism and Response to Gonadotropin-releasing Hormone Analogues in Primary Severe Insulin Resistance[J]. J Clin Endocrinol Metab, 2021, 106(8):2367-2383. doi: 10.1210/clinem/dgab275. doi: 10.1210/clinem/dgab275
[11]	徐芳, 孙淼, 郝松莉, 等. 多囊卵巢综合征不孕症患者胰岛素抵抗和临床特征的相关性分析[J]. 辽宁中医杂志, 2022, 49(7):13-16. doi: 10.13192/j.issn.1000-1719.2022.07.004. doi: 10.13192/j.issn.1000-1719.2022.07.004
	徐芳, 孙淼, 郝松莉, 等. 多囊卵巢综合征不孕症患者胰岛素抵抗和临床特征的相关性分析[J]. 辽宁中医杂志, 2022, 49(7):13-16. doi: 10.13192/j.issn.1000-1719.2022.07.004. doi: 10.13192/j.issn.1000-1719.2022.07.004
[12]	Chien YJ, Chang CY, Wu MY, et al. Effects of Curcumin on Glycemic Control and Lipid Profile in Polycystic Ovary Syndrome: Systematic Review with Meta-Analysis and Trial Sequential Analysis[J]. Nutrients, 2021, 13(2):684. doi: 10.3390/nu13020684. doi: 10.3390/nu13020684
	Chien YJ, Chang CY, Wu MY, et al. Effects of Curcumin on Glycemic Control and Lipid Profile in Polycystic Ovary Syndrome: Systematic Review with Meta-Analysis and Trial Sequential Analysis[J]. Nutrients, 2021, 13(2):684. doi: 10.3390/nu13020684. doi: 10.3390/nu13020684
[13]	吴亚妹, 马宁, 黄兹宝, 等. 胰岛素抵抗影响多囊卵巢综合征发病及机制的研究进展[J]. 生殖医学杂志, 2021, 30(9):1247-1251. doi: 10.3969/j.issn.1004-3845.2021.09.023. doi: 10.3969/j.issn.1004-3845.2021.09.023
	吴亚妹, 马宁, 黄兹宝, 等. 胰岛素抵抗影响多囊卵巢综合征发病及机制的研究进展[J]. 生殖医学杂志, 2021, 30(9):1247-1251. doi: 10.3969/j.issn.1004-3845.2021.09.023. doi: 10.3969/j.issn.1004-3845.2021.09.023
[14]	陆新虹, 杨海燕, 罗佐杰, 等. 不同胰岛素抵抗状态下多囊卵巢综合征患者内分泌指标与卵巢超声特征的相关性研究[J]. 中国糖尿病杂志, 2015, 23(1):40-42. doi: 10.3969/j.issn.1006-6187.2015.01.011. doi: 10.3969/j.issn.1006-6187.2015.01.011
	陆新虹, 杨海燕, 罗佐杰, 等. 不同胰岛素抵抗状态下多囊卵巢综合征患者内分泌指标与卵巢超声特征的相关性研究[J]. 中国糖尿病杂志, 2015, 23(1):40-42. doi: 10.3969/j.issn.1006-6187.2015.01.011. doi: 10.3969/j.issn.1006-6187.2015.01.011
[15]	Li X, Yang D, Pan P, et al. The Degree of Menstrual Disturbance Is Associated With the Severity of Insulin Resistance in PCOS[J]. Front Endocrinol(Lausanne), 2022, 13:873726. doi: 10.3389/fendo.2022.873726. doi: 10.3389/fendo.2022.873726
	Li X, Yang D, Pan P, et al. The Degree of Menstrual Disturbance Is Associated With the Severity of Insulin Resistance in PCOS[J]. Front Endocrinol(Lausanne), 2022, 13:873726. doi: 10.3389/fendo.2022.873726. doi: 10.3389/fendo.2022.873726
[16]	Kicińska AM, Stachowska A, Kajdy A, et al. Successful Implementation of Menstrual Cycle Biomarkers in the Treatment of Infertility in Polycystic Ovary Syndrome-Case Report[J]. Healthcare(Basel), 2023, 11(4):616. doi: 10.3390/healthcare11040616. doi: 10.3390/healthcare11040616
	Kicińska AM, Stachowska A, Kajdy A, et al. Successful Implementation of Menstrual Cycle Biomarkers in the Treatment of Infertility in Polycystic Ovary Syndrome-Case Report[J]. Healthcare(Basel), 2023, 11(4):616. doi: 10.3390/healthcare11040616. doi: 10.3390/healthcare11040616
[17]	Niu J, Lu M, Liu B. Association between insulin resistance and abnormal menstrual cycle in Chinese patients with polycystic ovary syndrome[J]. J Ovarian Res, 2023, 16(1):45. doi: 10.1186/s13048-023-01122-4. doi: 10.1186/s13048-023-01122-4
	Niu J, Lu M, Liu B. Association between insulin resistance and abnormal menstrual cycle in Chinese patients with polycystic ovary syndrome[J]. J Ovarian Res, 2023, 16(1):45. doi: 10.1186/s13048-023-01122-4. doi: 10.1186/s13048-023-01122-4
[18]	Brower M, Brennan K, Pall M, et al. The severity of menstrual dysfunction as a predictor of insulin resistance in PCOS[J]. J Clin Endocrinol Metab, 2013, 98(12): E1967-E1971. doi: 10.1210/jc.2013-2815. doi: 10.1210/jc.2013-2815
	Brower M, Brennan K, Pall M, et al. The severity of menstrual dysfunction as a predictor of insulin resistance in PCOS[J]. J Clin Endocrinol Metab, 2013, 98(12): E1967-E1971. doi: 10.1210/jc.2013-2815. doi: 10.1210/jc.2013-2815
[19]	童一希. 多囊卵巢综合征患者月经周期异常与糖脂代谢及胰岛功能相关性[J]. 中国计划生育学杂志, 2021, 29(9):1902-1906. doi: 10.3969/j.issn.1004-8189.2021.09.028. doi: 10.3969/j.issn.1004-8189.2021.09.028
	童一希. 多囊卵巢综合征患者月经周期异常与糖脂代谢及胰岛功能相关性[J]. 中国计划生育学杂志, 2021, 29(9):1902-1906. doi: 10.3969/j.issn.1004-8189.2021.09.028. doi: 10.3969/j.issn.1004-8189.2021.09.028
[20]	Ezeh U, Pisarska MD, Azziz R. Association of severity of menstrual dysfunction with hyperinsulinemia and dysglycemia in polycystic ovary syndrome[J]. Hum Reprod, 2022, 37(3):553-564. doi: 10.1093/humrep/deac001. doi: 10.1093/humrep/deac001
	Ezeh U, Pisarska MD, Azziz R. Association of severity of menstrual dysfunction with hyperinsulinemia and dysglycemia in polycystic ovary syndrome[J]. Hum Reprod, 2022, 37(3):553-564. doi: 10.1093/humrep/deac001. doi: 10.1093/humrep/deac001
[21]	尹丽红, 焦琳, 陈裕, 等. 多囊卵巢综合征大鼠子宫内膜中PI3K/AKT通路相关蛋白表达异常与胰岛素抵抗的关系[J]. 中国实验动物学报, 2022, 30(6):777-783. doi: 10.3969/j.issn.1005-4847.2022.06.006. doi: 10.3969/j.issn.1005-4847.2022.06.006
	尹丽红, 焦琳, 陈裕, 等. 多囊卵巢综合征大鼠子宫内膜中PI3K/AKT通路相关蛋白表达异常与胰岛素抵抗的关系[J]. 中国实验动物学报, 2022, 30(6):777-783. doi: 10.3969/j.issn.1005-4847.2022.06.006. doi: 10.3969/j.issn.1005-4847.2022.06.006
[22]	金婕, 熊文倩, 刘义. 上皮-间质转化和蜕膜化与子宫内膜容受性[J]. 国际妇产科学杂志, 2022, 49(3):325-329. doi: 10.12280/gjfckx.20210881. doi: 10.12280/gjfckx.20210881
	金婕, 熊文倩, 刘义. 上皮-间质转化和蜕膜化与子宫内膜容受性[J]. 国际妇产科学杂志, 2022, 49(3):325-329. doi: 10.12280/gjfckx.20210881. doi: 10.12280/gjfckx.20210881
[23]	Zhang C, Yang C, Li N, et al. Elevated insulin levels compromise endometrial decidualization in mice with decrease in uterine apoptosis in early-stage pregnancy[J]. Arch Toxicol, 2019, 93(12):3601-3615. doi: 10.1007/s00204-019-02601-8. doi: 10.1007/s00204-019-02601-8 pmid: 31642978
	Zhang C, Yang C, Li N, et al. Elevated insulin levels compromise endometrial decidualization in mice with decrease in uterine apoptosis in early-stage pregnancy[J]. Arch Toxicol, 2019, 93(12):3601-3615. doi: 10.1007/s00204-019-02601-8. doi: 10.1007/s00204-019-02601-8 pmid: 31642978
[24]	Sumarac-Dumanovic M, Apostolovic M, Janjetovic K, et al. Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome[J]. Mol Cell Endocrinol, 2017, 440:116-124. doi: 10.1016/j.mce.2016.11.009. doi: S0303-7207(16)30469-5 pmid: 27845161
	Sumarac-Dumanovic M, Apostolovic M, Janjetovic K, et al. Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome[J]. Mol Cell Endocrinol, 2017, 440:116-124. doi: 10.1016/j.mce.2016.11.009. doi: S0303-7207(16)30469-5 pmid: 27845161
[25]	Bai X, Zheng L, Li D, et al. Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review[J]. Reprod Biol Endocrinol, 2021, 19(1):122. doi: 10.1186/s12958-021-00802-4. doi: 10.1186/s12958-021-00802-4
	Bai X, Zheng L, Li D, et al. Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review[J]. Reprod Biol Endocrinol, 2021, 19(1):122. doi: 10.1186/s12958-021-00802-4. doi: 10.1186/s12958-021-00802-4
[26]	Chang EM, Han JE, Seok HH, et al. Insulin resistance does not affect early embryo development but lowers implantation rate in in vitro maturation-in vitro fertilization-embryo transfer cycle[J]. Clin Endocrinol(Oxf), 2013, 79(1):93-99. doi: 10.1111/cen.12099. doi: 10.1111/cen.12099
	Chang EM, Han JE, Seok HH, et al. Insulin resistance does not affect early embryo development but lowers implantation rate in in vitro maturation-in vitro fertilization-embryo transfer cycle[J]. Clin Endocrinol(Oxf), 2013, 79(1):93-99. doi: 10.1111/cen.12099. doi: 10.1111/cen.12099
[27]	Guo F, Gong Z, Fernando T, et al. The Lipid Profiles in Different Characteristics of Women with PCOS and the Interaction Between Dyslipidemia and Metabolic Disorder States: A Retrospective Study in Chinese Population[J]. Front Endocrinol(Lausanne), 2022, 13:892125. doi: 10.3389/fendo.2022.892125. doi: 10.3389/fendo.2022.892125
	Guo F, Gong Z, Fernando T, et al. The Lipid Profiles in Different Characteristics of Women with PCOS and the Interaction Between Dyslipidemia and Metabolic Disorder States: A Retrospective Study in Chinese Population[J]. Front Endocrinol(Lausanne), 2022, 13:892125. doi: 10.3389/fendo.2022.892125. doi: 10.3389/fendo.2022.892125
[28]	赵红莉, 韦洪江, 贾晓江, 等. 多囊卵巢综合征伴与不伴胰岛素抵抗患者糖脂代谢情况比较[J]. 中国妇幼保健, 2020, 35(12):2183-2185. doi: 10.19829/j.zgfybj.issn.1001-4411.2020.12.012. doi: 10.19829/j.zgfybj.issn.1001-4411.2020.12.012
	赵红莉, 韦洪江, 贾晓江, 等. 多囊卵巢综合征伴与不伴胰岛素抵抗患者糖脂代谢情况比较[J]. 中国妇幼保健, 2020, 35(12):2183-2185. doi: 10.19829/j.zgfybj.issn.1001-4411.2020.12.012. doi: 10.19829/j.zgfybj.issn.1001-4411.2020.12.012
[29]	Sakurai Y, Kubota N, Yamauchi T, et al. Role of Insulin Resistance in MAFLD[J]. Int J Mol Sci, 2021, 22(8):4156. doi: 10.3390/ijms22084156. doi: 10.3390/ijms22084156
	Sakurai Y, Kubota N, Yamauchi T, et al. Role of Insulin Resistance in MAFLD[J]. Int J Mol Sci, 2021, 22(8):4156. doi: 10.3390/ijms22084156. doi: 10.3390/ijms22084156
[30]	Manzano-Nunez R, Santana-Dominguez M, Rivera-Esteban J, et al. Non-Alcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome: A Systematic Review, Meta-Analysis, and Meta-Regression[J]. J Clin Med, 2023, 12(3):856. doi: 10.3390/jcm12030856. doi: 10.3390/jcm12030856
	Manzano-Nunez R, Santana-Dominguez M, Rivera-Esteban J, et al. Non-Alcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome: A Systematic Review, Meta-Analysis, and Meta-Regression[J]. J Clin Med, 2023, 12(3):856. doi: 10.3390/jcm12030856. doi: 10.3390/jcm12030856
[31]	Harsha Varma S, Tirupati S, Pradeep T, et al. Insulin resistance and hyperandrogenemia independently predict nonalcoholic fatty liver disease in women with polycystic ovary syndrome[J]. Diabetes Metab Syndr, 2019, 13(2):1065-1069. doi: 10.1016/j.dsx.2018.12.020. doi: S1871-4021(18)30595-2 pmid: 31336445
	Harsha Varma S, Tirupati S, Pradeep T, et al. Insulin resistance and hyperandrogenemia independently predict nonalcoholic fatty liver disease in women with polycystic ovary syndrome[J]. Diabetes Metab Syndr, 2019, 13(2):1065-1069. doi: 10.1016/j.dsx.2018.12.020. doi: S1871-4021(18)30595-2 pmid: 31336445
[32]	Macut D, Tziomalos K, Božić-Antić I, et al. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome[J]. Hum Reprod, 2016, 31(6):1347-1353. doi: 10.1093/humrep/dew076. doi: 10.1093/humrep/dew076
	Macut D, Tziomalos K, Božić-Antić I, et al. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome[J]. Hum Reprod, 2016, 31(6):1347-1353. doi: 10.1093/humrep/dew076. doi: 10.1093/humrep/dew076
[33]	Giannouli A, Efthymiou V, Konidari M, et al. The Burden of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study[J]. J Clin Med, 2023, 12(2):557. doi: 10.3390/jcm12020557. doi: 10.3390/jcm12020557
	Giannouli A, Efthymiou V, Konidari M, et al. The Burden of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study[J]. J Clin Med, 2023, 12(2):557. doi: 10.3390/jcm12020557. doi: 10.3390/jcm12020557
[34]	Shengir M, Chen T, Guadagno E, et al. Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis[J]. JGH Open, 2021, 5(4):434-445. doi: 10.1002/jgh3.12512. doi: 10.1002/jgh3.12512 pmid: 33860093
	Shengir M, Chen T, Guadagno E, et al. Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis[J]. JGH Open, 2021, 5(4):434-445. doi: 10.1002/jgh3.12512. doi: 10.1002/jgh3.12512 pmid: 33860093
[35]	袁莹莹, 赵君利. 多囊卵巢综合征流行病学特点[J]. 中国实用妇科与产科杂志, 2019, 35(3):261-264. doi: 10.19538/j.fk2019030102. doi: 10.19538/j.fk2019030102
	袁莹莹, 赵君利. 多囊卵巢综合征流行病学特点[J]. 中国实用妇科与产科杂志, 2019, 35(3):261-264. doi: 10.19538/j.fk2019030102. doi: 10.19538/j.fk2019030102
[36]	Ezeh U, Chen IY, Chen YH, et al. Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell Function[J]. J Clin Endocrinol Metab, 2020, 105(7):e2408-e2420. doi: 10.1210/clinem/dgaa235. doi: 10.1210/clinem/dgaa235
	Ezeh U, Chen IY, Chen YH, et al. Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell Function[J]. J Clin Endocrinol Metab, 2020, 105(7):e2408-e2420. doi: 10.1210/clinem/dgaa235. doi: 10.1210/clinem/dgaa235
[37]	Cardoso NS, Ribeiro VB, Dutra S, et al. Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin[J]. Arch Endocrinol Metab, 2020, 64(1):4-10. doi: 10.20945/2359-3997000000197. doi: S2359-39972020000100004 pmid: 32187268
	Cardoso NS, Ribeiro VB, Dutra S, et al. Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin[J]. Arch Endocrinol Metab, 2020, 64(1):4-10. doi: 10.20945/2359-3997000000197. doi: S2359-39972020000100004 pmid: 32187268
[38]	Behboudi-Gandevani S, Ramezani Tehrani F, Rostami Dovom M, et al. Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies[J]. Gynecol Endocrinol, 2016, 32(5):343-353. doi: 10.3109/09513590.2015.1117069. doi: 10.3109/09513590.2015.1117069 pmid: 27052492
	Behboudi-Gandevani S, Ramezani Tehrani F, Rostami Dovom M, et al. Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies[J]. Gynecol Endocrinol, 2016, 32(5):343-353. doi: 10.3109/09513590.2015.1117069. doi: 10.3109/09513590.2015.1117069 pmid: 27052492
[39]	Oguz SH, İdilman I, Helvaci N, et al. Tissue fat quantification by magnetic resonance imaging: proton density fat fraction in polycystic ovary syndrome[J]. Reprod Biomed Online, 2020, 41(2):329-334. doi: 10.1016/j.rbmo.2020.04.024. doi: S1472-6483(20)30266-2 pmid: 32576491
	Oguz SH, İdilman I, Helvaci N, et al. Tissue fat quantification by magnetic resonance imaging: proton density fat fraction in polycystic ovary syndrome[J]. Reprod Biomed Online, 2020, 41(2):329-334. doi: 10.1016/j.rbmo.2020.04.024. doi: S1472-6483(20)30266-2 pmid: 32576491
[40]	Pereira-Eshraghi CF, Chiuzan C, Zhang Y, et al. Obesity and Insulin Resistance, Not Polycystic Ovary Syndrome, Are Independent Predictors of Bone Mineral Density in Adolescents and Young Women[J]. Horm Res Paediatr, 2019, 92(6):365-371. doi: 10.1159/000507079. doi: 10.1159/000507079
	Pereira-Eshraghi CF, Chiuzan C, Zhang Y, et al. Obesity and Insulin Resistance, Not Polycystic Ovary Syndrome, Are Independent Predictors of Bone Mineral Density in Adolescents and Young Women[J]. Horm Res Paediatr, 2019, 92(6):365-371. doi: 10.1159/000507079. doi: 10.1159/000507079
[41]	Salari-Moghaddam A, Sadeghi O, Keshteli AH, et al. Metformin use and risk of fracture: a systematic review and meta-analysis of observational studies[J]. Osteoporos Int, 2019, 30(6):1167-1173. doi: 10.1007/s00198-019-04948-1. doi: 10.1007/s00198-019-04948-1 pmid: 30927035
	Salari-Moghaddam A, Sadeghi O, Keshteli AH, et al. Metformin use and risk of fracture: a systematic review and meta-analysis of observational studies[J]. Osteoporos Int, 2019, 30(6):1167-1173. doi: 10.1007/s00198-019-04948-1. doi: 10.1007/s00198-019-04948-1 pmid: 30927035
[42]	Piovezan JM, Premaor MO, Comim FV. Negative impact of polycystic ovary syndrome on bone health: a systematic review and meta-analysis[J]. Hum Reprod Update, 2019, 25(5):633-645. doi: 10.1093/humupd/dmz020. doi: 10.1093/humupd/dmz020 pmid: 31374576
	Piovezan JM, Premaor MO, Comim FV. Negative impact of polycystic ovary syndrome on bone health: a systematic review and meta-analysis[J]. Hum Reprod Update, 2019, 25(5):633-645. doi: 10.1093/humupd/dmz020. doi: 10.1093/humupd/dmz020 pmid: 31374576
[43]	Karadağ C, Yoldemir T, Gogas Yavuz D. Determinants of low bone mineral density in premenopausal polycystic ovary syndrome patients[J]. Gynecol Endocrinol, 2017, 33(3):234-237. doi: 10.1080/09513590.2016.1250256. doi: 10.1080/09513590.2016.1250256 pmid: 27908213
	Karadağ C, Yoldemir T, Gogas Yavuz D. Determinants of low bone mineral density in premenopausal polycystic ovary syndrome patients[J]. Gynecol Endocrinol, 2017, 33(3):234-237. doi: 10.1080/09513590.2016.1250256. doi: 10.1080/09513590.2016.1250256 pmid: 27908213
[44]	Aldhafiri FK, Abdelgawad FE, Mohamed Bakri GM, et al. Insulin Resistance and Bone Metabolism Markers in Women with Polycystic Ovary Syndrome: A Cross-Sectional Study on Females from the Islamic University Medical Center[J]. Medicina(Kaunas), 2023, 59(3):593. doi: 10.3390/medicina59030593. doi: 10.3390/medicina59030593
	Aldhafiri FK, Abdelgawad FE, Mohamed Bakri GM, et al. Insulin Resistance and Bone Metabolism Markers in Women with Polycystic Ovary Syndrome: A Cross-Sectional Study on Females from the Islamic University Medical Center[J]. Medicina(Kaunas), 2023, 59(3):593. doi: 10.3390/medicina59030593. doi: 10.3390/medicina59030593