Non-alcoholic fatty liver disease (NAFLD) is a chronic non-communicable disease. It is a metabolic syndrome (MS) in the liver. Menopause is a physiological phenomenon of women due to the decline of ovarian function, which is characterized by the deterioration of hypothalamic-pituitary function. Clinical and epidemiological studies have shown that the incidence trend of NAFLD has gender differences and is related to metabolic parameters such as glucose, lipids, and blood uric acid. The incidence of NAFLD in premenopausal women is lower than that in males, while the incidence of NAFLD in postmenopausal women gradually increases to the same as that in males. The mechanism may be mainly related to the changes of sex hormones in postmenopausal women (mainly the decrease of estrogen). The changes of sex hormones such as the decreased levels of estrogen and sex hormone binding globulin (SHBG) and the relatively increased level of androgen can increase the incidence of MS components such as abdominal obesity, abnormal blood lipid metabolism and insulin resistance (IR), making menopause an important independent risk factor for NAFLD in women. Estrogen, androgen receptor antagonists and phytoestrogens can improve hepatic steatosis and IR through many ways, reduce the severity of NAFLD and delay its progression to liver fibrosis, which have certain therapeutic significance for postmenopausal women with NAFLD, but also have some limitations. This paper reviews the research progress in the relationship between menopause and NAFLD in recent years, so as to provide ideas and reference for the prevention and treatment of NAFLD in postmenopausal women.
LIU Weiwei, WANG Long. Research progress in the correlation and treatment of menopause and non-alcoholic fatty liver disease in women. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2023, 43(1): 125-131 doi:10.3969/j.issn.1674-8115.2023.01.017
绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍。女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］。此外，绝经影响女性骨代谢。绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素。有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加。维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一。雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］。研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高。绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］。高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用。肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］。过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压。
LIU Weiwei proposed the idea of drafting the article, collected the literature and completed the writing. WANG Long was in charge of the content design and revision of the article. Both authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
Both authors disclose no relevant conflict of interests.
WANG Z L, XU M, HU Z G, et al. Sex-specific prevalence of fatty liver disease and associated metabolic factors in Wuhan, south central China[J]. Eur J Gastroenterol Hepatol, 2014, 26(9): 1015-1021.
LONG M T, PEDLEY A, MASSARO J M, et al. A simple clinical model predicts incident hepatic steatosis in a community-based cohort: the Framingham Heart Study[J]. Liver Int, 2018, 38(8): 1495-1503.
KLAIR J S, YANG J D, ABDELMALEK M F, et al. A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease[J]. Hepatology, 2016, 64(1): 85-91.
PARK S H, PARK Y E, LEE J, et al. Lack of association between early menopause and non-alcoholic fatty liver disease in postmenopausal women[J]. Climacteric, 2020, 23(2): 173-177.
JABALLAH A, SOLTANI I, BAHIA W, et al. The relationship between menopause and metabolic syndrome: experimental and bioinformatics analysis[J]. Biochem Genet, 2021, 59(6): 1558-1581.
CHUNG S I, RYU S N, KANG M Y. Changes in bone metabolism and antioxidant defense systems in menopause-induced rats fed bran extract from dark purple rice (Oryza sativa L. Cv. Superjami)[J]. Nutrients, 2021, 13(9): 2926.
DUPUIS M L, PAGANO M T, PIERDOMINICI M, et al. The role of vitamin D in autoimmune diseases: could sex make the difference?[J]. Biol Sex Differ, 2021, 12(1): 12.
WAN H, ZHANG K, WANG Y Y, et al. The associations between gonadal hormones and serum uric acid levels in men and postmenopausal women with diabetes[J]. Front Endocrinol (Lausanne), 2020, 11: 55.
WANG X H, JIANG W R, ZHANG M Y, et al. The visceral fat area to leg muscle mass ratio is significantly associated with the risk of hyperuricemia among women: a cross-sectional study[J]. Biol Sex Differ, 2021, 12(1): 17.
LIU Q, NIU C Y. From "two hit theory" to "multiple hit theory": implications of evolution of pathogenesis concepts for treatment of non-alcoholic fatty liver disease[J]. World Chinese Journal of Digestology, 2019, 27(19): 1171-1178.
YARIBEYGI H, FARROKHI F R, BUTLER A E, et al. Insulin resistance: review of the underlying molecular mechanisms[J]. J Cell Physiol, 2019, 234(6): 8152-8161.
VENETSANAKI V, POLYZOS S A. Menopause and non-alcoholic fatty liver disease: a review focusing on therapeutic perspectives[J]. Curr Vasc Pharmacol, 2019, 17(6): 546-555.
DE MUTSERT R, GAST K, WIDYA R, et al. Associations of abdominal subcutaneous and visceral fat with insulin resistance and secretion differ between men and women: the Netherlands epidemiology of obesity study[J]. Metab Syndr Relat Disord, 2018, 16(1): 54-63.
ZENG X, XIE Y J, LIU Y T, et al. Polycystic ovarian syndrome: correlation between hyperandrogenism, insulin resistance and obesity[J]. Clin Chim Acta, 2020, 502: 214-221.
WANG J, WU D C, GUO H, et al. Hyperandrogenemia and insulin resistance: the chief culprit of polycystic ovary syndrome[J]. Life Sci, 2019, 236: 116940.
KUR P, KOLASA-WOŁOSIUK A, MISIAKIEWICZ-HAS K, et al. Sex hormone-dependent physiology and diseases of liver[J]. Int J Environ Res Public Health, 2020, 17(8): 2620.
XIA F Z, XU X, ZHAI H L, et al. Castration-induced testosterone deficiency increases fasting glucose associated with hepatic and extra-hepatic insulin resistance in adult male rats[J]. Reprod Biol Endocrinol, 2013, 11: 106.
QU X Q, DONNELLY R. Sex hormone-binding globulin (SHBG) as an early biomarker and therapeutic target in polycystic ovary syndrome[J]. Int J Mol Sci, 2020, 21(21): 8191.
SOWERS M, DERBY C, JANNAUSCH M L, et al. Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN[J]. J Clin Endocrinol Metab, 2003, 88(10): 4904-4910.
YAMAZAKI H, KUSHIYAMA A, SAKODA H, et al. Protective effect of sex hormone-binding globulin against metabolic syndrome: in vitro evidence showing anti-inflammatory and lipolytic effects on adipocytes and macrophages[J]. Mediators Inflamm, 2018, 2018: 3062319.
YANG M, LIU Q L, HUANG T L, et al. Dysfunction of estrogen-related receptor α-dependent hepatic VLDL secretion contributes to sex disparity in NAFLD/NASH development[J]. Theranostics, 2020, 10(24): 10874-10891.
BITIRIM C V, OZER Z B, AKCALI K C. Estrogen receptor α regulates the expression of adipogenic genes genetically and epigenetically in rat bone marrow-derived mesenchymal stem cells[J]. Peer J, 2021, 9: e12071.
LI F J, WEI S N, WANG L Y, et al. Estrogen reduces lipid deposition in liver cells by inhibiting perilipin 2[J]. Journal of Cardiovascular and Pulmonary Diseases, 2018, 37(7): 687-691.
IWASA T, MATSUZAKI T, MAYILA Y, et al. Oxytocin treatment reduced food intake and body fat and ameliorated obesity in ovariectomized female rats[J]. Neuropeptides, 2019, 75: 49-57.
MA H, SPRECHER H W, KOLATTUKUDY P E. Estrogen-induced production of a peroxisome proliferator-activated receptor (PPAR) ligand in a PPARγ-expressing tissue[J]. J Biol Chem, 1998, 273(46): 30131-30138.
NIRANJAN M K, KOIRI R K, SRIVASTAVA R. Expression of estrogen receptor α in response to stress and estrogen antagonist tamoxifen in the shell gland of Gallus gallus domesticus: involvement of anti-oxidant system and estrogen[J]. Stress, 2021, 24(3): 261-272.
BESSE-PATIN A, LÉVEILLÉ M, OROPEZA D, et al. Estrogen signals through peroxisome proliferator-activated receptor‑γ coactivator 1α to reduce oxidative damage associated with diet-induced fatty liver disease[J]. Gastroenterology, 2017, 152(1): 243-256.
CORTES E, LACHOWSKI D, RICE A, et al. Tamoxifen mechanically deactivates hepatic stellate cells via the G protein-coupled estrogen receptor[J]. Oncogene, 2019, 38(16): 2910-2922.
LEE Y H, SON J Y, KIM K S, et al. Estrogen deficiency potentiates thioacetamide-induced hepatic fibrosis in sprague-dawley rats[J]. Int J Mol Sci, 2019, 20(15): 3709.
SHIMIZU I, MIZOBUCHI Y, YASUDA M, et al. Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro[J]. Gut, 1999, 44(1): 127-136.
PAPAEFTHYMIOU A, DOULBERIS M, KARAFYLLIDOU K, et al. Effect of spironolactone on pharmacological treatment of nonalcoholic fatty liver disease[J]. Minerva Endocrinol (Torino), 2021. DOI: 10. 23736/S2724-6507.21.03564-8.
ZAMANI-GARMSIRI F, HASHEMNIA S M R, SHABANI M, et al. Combination of metformin and genistein alleviates non-alcoholic fatty liver disease in high-fat diet-fed mice[J]. J Nutr Biochem, 2021, 87: 108505.
LUO Z H, LIU Z W, MAO Y, et al. Cajanolactone A, a stilbenoid from Cajanus cajan, prevents ovariectomy-induced obesity and liver steatosis in mice fed a regular diet[J]. Phytomedicine, 2020, 78: 153290.
CHEN Y R, QUE R Y, ZHANG N, et al. Saikosaponin-d alleviates hepatic fibrosis through regulating GPER1/autophagy signaling[J]. Mol Biol Rep, 2021, 48(12): 7853-7863.
LIN L B, ZHOU M G, QUE R Y, et al. Saikosaponin-d protects against liver fibrosis by regulating the estrogen receptor‑β/NLRP3 inflammasome pathway[J]. Biochem Cell Biol, 2021, 99(5): 666-674.
... 绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍.女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］.此外，绝经影响女性骨代谢.绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素.有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加.维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一.雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］.研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高.绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］.高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用.肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］.过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压. ...
2
... 绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍.女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］.此外，绝经影响女性骨代谢.绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素.有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加.维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一.雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］.研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高.绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］.高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用.肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］.过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压. ...
... 绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍.女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］.此外，绝经影响女性骨代谢.绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素.有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加.维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一.雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］.研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高.绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］.高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用.肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］.过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压. ...
1
... 绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍.女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］.此外，绝经影响女性骨代谢.绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素.有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加.维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一.雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］.研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高.绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］.高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用.肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］.过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压. ...
1
... 绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍.女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］.此外，绝经影响女性骨代谢.绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素.有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加.维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一.雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］.研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高.绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］.高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用.肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］.过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压. ...
1
... 绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍.女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］.此外，绝经影响女性骨代谢.绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素.有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加.维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一.雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］.研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高.绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］.高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用.肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］.过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压. ...
1
... 绝经是MS的独立危险因素，相关研究［7］表明女性绝经后MS发病率是绝经前的2.46倍.女性绝经前后MS疾病相关的各代谢组分对照显示，绝经后MS组体质量指数（body mass index，BMI）、三酰甘油、空腹胰岛素及胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）高于绝经前MS组［8］.此外，绝经影响女性骨代谢.绝经后雌激素缺乏导致的氧化应激增加是老年女性骨质疏松的危险因素.有研究［9］报道了去卵巢雌性大鼠骨钙素、碱性磷酸酶以及Ⅰ型胶原羧基末端肽水平升高是因为其肝脏组织和红细胞中抗氧化酶活性显著降低，使得氧化应激增加，导致骨丢失、骨转换增加.维生素D缺乏所致的肠道钙磷吸收障碍和骨钙沉积减少也是骨代谢异常因素之一.雌激素通过降低维生素D代谢酶CYP24A1（cytochrome P450 family 24 subfamily A member 1）的表达减少维生素D的失活，从而增强维生素D的功能，促进其积累，并可增加维生素D受体的表达［10］.研究［11］发现维生素D缺乏患者的血清葡萄糖浓度、总胆固醇、低密度脂蛋白、三酰甘油、糖基化血红蛋白和BMI升高.绝经后女性血尿酸水平随着脱氢表雄酮、总睾酮和黄体生成素的增加而显著升高［12］.高尿酸血症患者的血尿酸水平与内脏脂肪含量呈正相关，血尿酸水平升高可引起炎症反应和糖脂代谢紊乱，在MS的形成中起重要作用.肥胖可通过增加尿酸合成并抑制其排泄而引起高尿酸血症，而尿酸升高又可通过促进果糖转化为脂肪加速内脏脂肪积累，在促进肥胖发展的同时导致氧化应激诱发脂肪细胞产生炎症［13］.过量脂肪组织在腹部蓄积与IR关系密切，随之而来的微血管损伤可引起血管壁炎症和高血压. ...
