多囊卵巢综合征雄激素质谱检测专家共识

doi:10.3969/j.issn.1673-8640.2023.03.001

摘要/Abstract

摘要：

多囊卵巢综合征（PCOS）是常见的育龄期女性内分泌疾病，也是导致女性不孕的主要因素。PCOS病理生理的主要问题是高雄激素血症。高雄激素血症可以通过生化检验或临床表现进行评估。目前，大多临床实验室常规开展的基于免疫学的雄激素检测方法存在诸多缺陷，如交叉反应、检测低浓度样本时准确性差、不同品牌试剂检测结果缺乏可比性，导致高雄激素血症评估时出现假阳性结果。液相色谱串联质谱（LC-MS/MS）具有灵敏度高、特异性强、线性范围宽、可多目标物同时检测等优势，是更高效的雄激素检测方法。基于临床和实验室循证医学证据，首都医科大学附属北京妇产医院和中国人体健康科技促进会生育力保护与保存专业委员会联合临床检验、妇科内分泌、质谱应用领域学者共同制定该专家共识，旨在为医疗机构开展PCOS雄激素检测提供建议指导。该专家共识的声明包括PCOS雄激素实验室检测项目和检测方法的建议，以及采用LC-MS/MS检测雄激素的挑战与应对。

关键词: 多囊卵巢综合征, 高雄激素血症, 液相色谱串联质谱

Abstract:

Polycystic ovary syndrome（PCOS） is one of the most common endocrine disorders in reproductive-age females，frequently leading to female infertility. Hyperandrogenemia plays a role in the pathogenesis of PCOS. Hyperandrogenemia can be evaluated by biochemical tests or clinical signs. At present，there are some limitations of immunology-based testing methods for androgen，such as cross-reaction，poor accuracy in low-concentration samples and lack of comparability among different reagent manufacturers，leading to false positivity. With the advantages of high sensitivity，high specificity，wide linear range and the capability of simultaneous determination of multiple molecules，liquid chromatography-tandem mass spectrometry（LC-MS/MS） becomes a good choice for androgen testing. On the basis of published clinical and laboratory evidence，Beijing Obstetrics and Gynecology Hospital of Capital Medical University，China Association for Promotion of Health Science and Technology-Fertility Protection and Preservation Committee，along with the experts in the clinical laboratory，gynecological endocrinology and mass spectrometry application relevant field made this consensus，in order to provide professional guidance in PCOS androgen testing in clinical laboratories. The consensus includes recommendations on types and methods of androgen testing for PCOS and challenges of androgen testing with LC-MS/MS.

Key words: Polycystic ovary syndrome, Hyperandrogenemia, Liquid chromatography-tandem mass spectrometry

中图分类号:

R446.1

多囊卵巢综合征雄激素质谱检测共识专家组. 多囊卵巢综合征雄激素质谱检测专家共识[J]. 检验医学, 2023, 38(3): 203-208.

Expert Group on the Consensus on Androgen Testing in Polycystic Ovary Syndrome China Association for Promotion of Health Science and Technology-Fertility Protection and Preservation Committee. Consensus on androgen testing in polycystic ovary syndrome[J]. Laboratory Medicine, 2023, 38(3): 203-208.

图/表 1

参考文献 34

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分析物名称	测定方法	检测效能
TT	CLIA、 LC-MS/MS	LC-MS/MS与CLIA测定TT的相关性较差（r=0.362，P<0.01）；采用LC-MS/MS和CLIA测定TT，诊断PCOS的曲线下面积分别为0.850和0.805，且CLIA的TT测定值整体偏高^[18]
DHEA-S	CLIA、 LC-MS/MS	在PCOS的诊断中，采用LC-MS/MS测定DHEA-S的效能（曲线下面积为0.789）显著优于采用CLIA测定DHEA-S（曲线下面积为0.661）（P<0.01）；LC-MS/MS对低浓度样本（pg/mL或ng/mL水平）和因分子结构相似导致的交叉反应严重且基质干扰大的分析物具有显著优势^[11]
DHEA	ELISA、 RIA、 LC-MS/MS	1）LC-MS/MS较RIA定量限更低、测量范围更宽、准确性更高^[26] 2）ELISA与LC-MS/MS测定DHEA的相关性一般（r=0.631，P<0.001）；一致性分析发现ELISA存在低估DHEA水平的趋势^[27]
DHT	ELISA、 RIA、 LC-MS/MS	1）RIA测定的血清DHT水平明显高于LC-MS/MS的测定结果 ^[28] 2）ELISA与LC-MS/MS的DHT测定结果成非线性，且一致性分析发现ELISA存在低估DHT水平的趋势^[27]，原因主要在于DHT的血清浓度远低于其他雄激素，免疫法的抗体灵敏度较低，且测量范围窄，无法准确定量DHT 3）RIA检测血清DHT会受前体睾酮对映体干扰，导致DHT测定值显著升高^[29]
A4	ELISA、 RIA、 CLIA、 LC-MS/MS	1）LC-MS/MS与RIA测定A4的相关性一般（r=0.632，P<0.01），LC-MS/MS测定的A4水平低于RIA的测定结果，在卵泡期偏差更大^[30] 2）ELISA与LC-MS/MS测定A4的相关性一般（r=0.735，P<0.001），且一致性分析发现ELISA存在高估A4水平的趋势^[25,27,31]

分析物名称	测定方法	检测效能
TT	CLIA、 LC-MS/MS	LC-MS/MS与CLIA测定TT的相关性较差（r=0.362，P<0.01）；采用LC-MS/MS和CLIA测定TT，诊断PCOS的曲线下面积分别为0.850和0.805，且CLIA的TT测定值整体偏高^[18]
DHEA-S	CLIA、 LC-MS/MS	在PCOS的诊断中，采用LC-MS/MS测定DHEA-S的效能（曲线下面积为0.789）显著优于采用CLIA测定DHEA-S（曲线下面积为0.661）（P<0.01）；LC-MS/MS对低浓度样本（pg/mL或ng/mL水平）和因分子结构相似导致的交叉反应严重且基质干扰大的分析物具有显著优势^[11]
DHEA	ELISA、 RIA、 LC-MS/MS	1）LC-MS/MS较RIA定量限更低、测量范围更宽、准确性更高^[26] 2）ELISA与LC-MS/MS测定DHEA的相关性一般（r=0.631，P<0.001）；一致性分析发现ELISA存在低估DHEA水平的趋势^[27]
DHT	ELISA、 RIA、 LC-MS/MS	1）RIA测定的血清DHT水平明显高于LC-MS/MS的测定结果 ^[28] 2）ELISA与LC-MS/MS的DHT测定结果成非线性，且一致性分析发现ELISA存在低估DHT水平的趋势^[27]，原因主要在于DHT的血清浓度远低于其他雄激素，免疫法的抗体灵敏度较低，且测量范围窄，无法准确定量DHT 3）RIA检测血清DHT会受前体睾酮对映体干扰，导致DHT测定值显著升高^[29]
A4	ELISA、 RIA、 CLIA、 LC-MS/MS	1）LC-MS/MS与RIA测定A4的相关性一般（r=0.632，P<0.01），LC-MS/MS测定的A4水平低于RIA的测定结果，在卵泡期偏差更大^[30] 2）ELISA与LC-MS/MS测定A4的相关性一般（r=0.735，P<0.001），且一致性分析发现ELISA存在高估A4水平的趋势^[25,27,31]