根据气相色谱-质谱分析多囊卵巢综合征患者的雄激素、黄体酮和糖皮质激素的代谢组学的研究

封面


如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅存取

详细

研究现实性。多囊卵巢综合征是一种常见的疾病。根据诊断标准，10-20%的育龄妇女可见此病，
占所有形式的高雄激素症综合征的70-80%。多囊卵巢综合征是一种具有多因素病因的异质性疾病，
以多种临床、内分泌和代谢紊乱为特征。在这方面，阐明甾体激素的生物合成和代谢特征、甾体生成酶的活性、寻找新的实验室标准以早期诊断和及时开始治疗是有意义的。

目的：根据气相色谱-质谱分析研究正常体重肥胖多囊卵巢综合征女性的雄激素、黄体酮和糖皮质激素的代谢组学。

研究材料和方法。本文对53例多囊卵巢综合征育龄妇女进行了检查。第一组包括30名体重正常、
年龄在22至29岁的女性。第二组包括23例肥胖患者，年龄为25-33岁，平均体重指数为35.3 ± 0.4 kg/m2。对照组包括25例健康女性，年龄为26 ± 0.6岁，体重指数正常，无高雄激素血症临床及生化体征。采用血清免疫测定方法测定促黄体激素、促卵泡激素、游离睾酮、17-羟孕甾酮和性激素结合球蛋白的水平。采75g的口服葡萄糖耐量试验测定葡萄糖负荷前后的血糖和胰岛
素水平。采用气相色谱-质谱分析对尿液中的类固醇成分进行了分析，并对样品制备规则进行了优化。
统计数据处理使用STATISTICA软件系统为WINDOWS（10版本）。患者的主要定量特征以中位数（Me）、
第25百分位和第75百分位（Q25-Q75）的形式表示。为了比较研究组的结果，使用非参数Mann-Whitney U检验。置信标准p < 0.05认为有统计学意义。

研究成果。本文对多囊卵巢综合征妇女的雄激素、糖皮质激素和孕激素代谢组学进行分析，并与
对照组相应指标进行比较。无肥胖的多囊卵巢综合征患者尿中雄烯二酮、脱氢表雄酮及其代谢
产物、17-羟基孕烯醇酮、孕三醇、5-en-孕烷的排泄量增加，而多囊卵巢综合征和肥胖的女性中，
尿中雄酮和脱氢表雄酮代谢产物（16-oxo-雄烯二醇和17β-雄烯二醇）的排泄量较对照组增加。无肥胖
的多囊卵巢综合征患者皮质醇和可的松四氢衍生物与11-oxo-孕三醇、孕三醇和17-羟基孕烯醇酮的比值较对照组降低，这是21-羟化酶功能不足的迹象。在患有多囊卵巢综合征和肥胖的女性中，
有四种迹象表明5α-还原酶酵酶活性增加，而在体重指数正常的多囊卵巢综合征患者中，这三个指标表明多囊卵巢综合征患者5α-还原酶活性不同程度，这取决于体重指数。

结果。气相色谱-质谱分析同时定量测定尿液中类固醇检测中雄激素代谢产物、黄体酮、雄烯二酮和糖皮质激素的5α和5β代谢产物，为多囊卵巢综合征的诊断开辟了新的机遇。

作者简介

Natalya Vorokhobina

North-Western State Medical University named after I.I. Mechnikov

编辑信件的主要联系方式.
Email: natalya.vorokhobina@szgmu.ru
ORCID iD: 0000-0002-9574-105X
SPIN 代码: 4062-6409

MD, PhD, DSci (Medicine), Professor, Head of the Department of Endocrinology named after academician V.G. Baranov

俄罗斯联邦, Saint Petersburg

Lyudmila Velikanova

North-Western State Medical University named after I.I. Mechnikov

Email: velikanova46@gmail.com
ORCID iD: 0000-0002-9352-4035

PhD, DSci (Biology), Professor, Head of the Research Laboratory of Chromatography

俄罗斯联邦, Saint Petersburg

Olga Glavnova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: o.glavnova@mail.ru
ORCID iD: 0000-0001-6087-252X

MD

俄罗斯联邦, Saint Petersburg

Ekaterina Malevanaya

North-Western State Medical University named after I.I. Mechnikov

Email: obedkovaev@gmail.com
ORCID iD: 0000-0003-0880-0814

PhD, Senior Researcher

俄罗斯联邦, Saint Petersburg

Ravilya Galakhova

North-Western State Medical University named after I.I. Mechnikov

Email: rgalakhova@gmail.com
ORCID iD: 0000-0003-3599-3199
SPIN 代码: 1865-2310

MD, PhD, Associate Professor

俄罗斯联邦, Saint Petersburg

Irina Matezius

North-Western State Medical University named after I.I. Mechnikov

Email: imatezius@rambler.ru
ORCID iD: 0000-0002-8694-9756
SPIN 代码: 7421-1610

MD, PhD, Associate Professor. The Department of Endocrinology named after academician V.G. Baranov

俄罗斯联邦, Saint Petersburg

参考

  1. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018;14(5):270-284. https://doi.org/10.1038/nrendo.2018.24.
  2. 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. 2010;25(2):544-551. https://doi.org/10.1093/humrep/dep399.
  3. Манухин И.Б., Геворкян М.А., Кушлинский Н.Е. Синдром поликистозных яичников. – М.: МИА, 2004. – 190 c. [Manukhin IB, Gevorkyan MA, Kushlinskiy NE. Sindrom polikistoznykh yaichnikov. Moscow: MIA; 2004. 190 p. (In Russ.)]
  4. Pasquali R, Gambineri A, Pagotto U. The impact of obesity on reproduction in women with polycystic ovary syndrome. BJOG. 2006;113(10):1148-1159. https://doi.org/10.1111/j.1471-0528.2006.00990.x.
  5. Cоболева Е.Л., Потин В.В., Тарасова М.А. Гирсутизм: пособие для врачей. – СПб., 2007. – 49 c. [Soboleva EL, PotinVV, Tarasova MA. Girsutism: posobie dlya vrachey. Saint Petersburg; 2007. 49 p. (In Russ.)]
  6. Hart R, Doherty DA. The potential implications of a PCOS diagnosis on a woman’s long-term health using data linkage. J Clin Endocrinol Metab. 2015;100(3):911-919. https://doi.org/10.1210/jc.2014-3886.
  7. Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol. 2012;120(5):1160-1175. https://doi.org/10.1097/aog.0b013e31826bb121.
  8. Papadakis G, Kandaraki E, Papalou O, et al. Is cardiovascular risk in women with PCOS a real risk? Current insights. Minerva Endocrinol. 2017;42(4):340-355. https://doi.org/ 10.23736/S0391-1977.17.02609-8.
  9. Haoula Z, Salman M, Atiomo W. Evaluating the association between endometrial cancer and polycystic ovary syndrome. Hum Reprod. 2012;27(5):1327-1331. https://doi.org/10.1093/humrep/des042.
  10. Setji TL, Brown AJ. Polycystic ovary syndrome: Update on diagnosis and treatment. Am J Med. 2014;127(10):912-919. https://doi.org/10.1016/j.amjmed.2014.04.017.
  11. Dumitrescu R, Mehedintu C, Briceag I, et al. The polycystic ovary syndrome: An update on metabolic and hormonal mechanisms. J Med Life. 2015;8(2):142-145.
  12. 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. 2004;81(1):19-25. https://doi.org/10.1016/j.fertnstert.2003.10.004.
  13. Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28-38.e25. https://doi.org/10.1016/j.fertnstert.2011.09.024.
  14. Moran C, Arriaga M, Rodriguez G, Moran S. Obesity differentially affects phenotypes of polycystic ovary syndrome. Int J Endocrinol. 2012;2012:317241. https://doi.org/10.1155/2012/317241.
  15. Panidis D, Tziomalos K, Misichronis G, et al. Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: A prospective study. Hum Reprod. 2012;27(2):541-549. https://doi.org/10.1093/ humrep/der418.
  16. Neves EM, Fonseca AM, Bagnoli VR, et al. Polycystic ovary syndrome: Correlation between phenotypes and metabolic syndrome. J Steroids Horm Sci. 2014;5(2):132. https://doi.org/10.4172/2157-7536.1000132.
  17. Goverde AJ, van Koert AJ, Eijkemans MJ, et al. Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus. Hum Reprod. 2009;24(3):710-717. https://doi.org/10.1093/humrep/den433.
  18. Teede HJ, Misso ML, Costello MF, et al. Erratum. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2019;34(2):388. https://doi.org/10.1093/humrep/dey363.
  19. Ehrmann DA. Metabolic dysfunction in PCOS: Relationship to obstructive sleep apnea. Steroids. 2012;77(4):290-294. https://doi.org/10.1016/j.steroids.2011.12.001.
  20. Pasquali R, Casimirri F. The impact of obesity on hyperandrogenism and polycystic ovary syndrome in premenopausal women. Clin Endocrinol. 1993;39(1):1-16. https://doi.org/10.1111/j.1365-2265.1993.tb01744.x.
  21. Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab. 1980;50(1):113-116. https://doi.org/10.1210/jcem-50-1-113.
  22. Dunaif A. Insulin resistance and the polycystic ovary syndrome: Mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774-800. https://doi.org/10.1210/edrv.18.6.0318.
  23. Qin KN, Rosenfield RL. Role of cytochrome P450c17 in polycystic ovary syndrome. Mol Cell Endocrinol. 1998;145(1-2): 111-121. https://doi.org/10.1016/s0303-7207(98)00177-4.
  24. Bremer AA, Miller WL. The serine phosphorylation hypothesis of polycystic ovary syndrome: A unifying mechanism for hyperandrogenemia and insulin resistance. Fertil Steril. 2008;89(5):1039-1048. https://doi.org/10.1016/j.fertnstert. 2008.02.091.
  25. Ворохобина Н.В., Татаринова М.В., Великанова Л.И., и др. Особенности метаболизма стероидных гормонов у женщин репродуктивного возраста с различными формами гиперандрогении // Вестник Северо-Западного государственного медицинского университета им. И.И. Мечникова. − 2016. − Т. 8. − № 3. − С. 42–49. [Vorokhobina NV, Tatarinova MV, Velikanova LI, et al. Features of steroid hormone metabolism in fertile age females with various forms of hyperandrogenism. Herald of the Northwestern State Medical University named after I.I. Mechnikov. 2016;8(3):42-49. (In Russ.)]
  26. Gambineri A, Vicennati V, Genghini S, et al. Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(6):2295-2302. https://doi.org/10.1210/jc. 2005-2222.
  27. Yuying D, Yifei Z, Shengxian L, et al. Steroid hormone profilingin obese and non obese women with polycystic ovary syndrome. Sci Rep. 2017;7(1):14156. https://doi.org/10.1038/s41598-017-14534-2.
  28. Матюшко М.В. Нарушения метаболизма стероидных гормонов у женщин репродуктивного возраста с ожирением и гиперандрогенией: автореф. дис. … канд. мед. наук. – СПб., 2018. – 23 с. [Matyushko MV. Narusheniya metabolizma steroidnykh gormonov u zhenshchin reproduktivnogo vozrasta s ozhireniem i giperandrogeniey. [dissertation] Saint Petersburg; 2018. 23 p. (In Russ.)]
  29. Setji TL, Brown AJ. Polycystic ovary syndrome: Update on diagnosis and treatment. Am J Med. 2014;127(10):912-919. https://doi.org/10.1016/j.amjmed.2014.04.017.
  30. Goodarzi MO, Carmina E, Azziz R. DHEA, DHEAS and PCOS. J Steroid Biochem Mol Biol. 2015;145:213-225. https://doi.org/10.1016/j.jsbmb.2014.06.003.
  31. Dhayat NA, Marti N, Kollmann Z, et al. Urinary steroid profiling in women hints at a diagnostic signature of the polycystic ovary syndrome: A pilot study considering neglected steroid metabolites. PLoS One. 2018;13(10):e0203903. https://doi.org/10.1371/journal.pone.0203903.
  32. Fassnacht M, Schlenz N, Schneider SB, et al. Beyond adrenal and ovarian androgen generation: Increased peripheral 5 alpha-reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(6):2760-2766. https://doi.org/10.1210/jc.2002-021875.
  33. Torchen LC, Idkowiak J, Fogel NR, et al. Evidence for Increased 5α-reductase activity during early childhood in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2016;101(5):2069-2075. https://doi.org/10.1210/jc.2015-3926.
  34. Dhayat NA, Marti N, Kollmann Z, et al. Urinary steroid profiling in women hints at a diagnostic signature of the polycystic ovary syndrome: A pilot study considering neglected steroid metabolites. PLoS One. 2018;13(10):e0203903. https://doi.org/10.1371/journal.pone.0203903.
  35. Gambineri A, Vicennati V, Genghini S, et al. Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(6):2295-2302. https://doi.org/10.1210/jc. 2005-2222.

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Vorokhobina N., Velikanova L., Glavnova O., Malevanaya E., Galakhova R., Matezius I., 2020

Creative Commons License
此作品已接受知识共享署名 4.0国际许可协议的许可

##common.cookie##