摘要
目的通过超高效液相色谱-串联质谱(UPLC-MS/MS)技术,建立健康育龄期(18~40岁)女性血清类固醇激素水平的质谱法参考区间,为后续多囊卵巢综合征(PCOS)患者的激素水平分析及诊断阈值确定提供依据。方法选取2024年6—9月中国医学科学院北京协和医院招募的223名年龄在18~40岁之间的健康女性作为样本,检测研究对象在月经周期任一时段血清中的多种类固醇激素水平,包括总睾酮(TT)、游离睾酮(FT)、雄烯二酮(A4)、脱氢表雄酮(DHEA)、脱氢表雄酮硫酸盐(DHEAS)、双氢睾酮(DHT)、孕酮、孕烯醇酮(Preg)、17-羟基孕烯醇酮(17-OHPreg)、17α-羟基孕酮(17α-OHP)、11-脱氧皮质醇(11S)、11-脱氧皮质酮(DOC)、皮质醇及醛固酮(ALD)。通过统计分析,确立这些激素在不同年龄段、月经周期阶段及采样时间的变化规律及特定参考区间。结果育龄女性血清中的类固醇激素水平受到多种因素的影响,表现出显著差异。(1)在雄激素指标中,TT、FT、A4、DHEA和DHEAS的水平随年龄增长呈现显著下降趋势(P<0.001),而DHT的水平则不受年龄变化的明显影响;(2)孕激素指标中,仅孕酮和17α-OHP在月经周期的不同阶段表现出显著差异(P<0.001),黄体期组的孕酮和17α-OHP水平显著高于卵泡期组,而Preg和17-OHPreg的水平并未显示出因月经周期而有所差异;(3)仅皮质醇水平呈现显著的昼夜变化(P<0.001),具体表现为早晨浓度显著高于下午。结论本研究不仅验证了皮质醇和孕酮等激素的已知生理特性,还详细描述了各项雄激素指标在不同年龄段的变化趋势,为后续PCOS患者的血清类固醇激素水平分析及诊断切点值提供了精确的时间、年龄和月经周期参考依据,有助于提高疾病的诊断准确性。
Objective:To establish reference intervals for serum steroid hormones in reproductive-age women using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)and to provide a basis for subsequent hormone level analysis and diagnostic threshold determination in patients with polycystic ovary syndrome(PCOS).Methods:A total of 223 healthy women aged between 18 and 40 years were enrolled as subjects.Serum levels of various steroid hormones,including total testosterone(TT),free testosterone(FT),androstenedione(A4),dehydroepiandrosterone(DHEA),dehydroepiandrosterone sulfate(DHEAS),dihydrotestosterone(DHT),progesterone,pregnenolone(Preg),17-hydroxypregnenolone(17-OHPreg),17α-hydroxyprogesterone(17α-OHP),11-deoxycortisol(11S),11-deoxycorticosterone(DOC),cortisol,and aldosterone(ALD),were measured at any phase of the menstrual cycle.Statistical analysis was performed to get the change patterns and to establish the specific reference intervals for these hormones based on different age groups,menstrual cycle phases,and sampling times.Results:The serum levels of steroid hormones in reproductive-age women were influenced by multiple factors,resulting in distinct reference intervals.Among the androgen indicators,the levels of TT,FT,A4,DHEA,and DHEAS showed a significant decreasing trend with age(P<0.001),while the level of DHT was not affected by age.Among the progestogen indicators,only the levels of progesterone and 17α-OHP exhibited significant differences across different phases of the menstrual cycle(P<0.001),the levels of progesterone and 17α-OHP in the luteal phase were significantly higher than those in the follicular phase,whereas the levels of Preg and 17-OHPreg were not influenced by the menstrual cycle.Only the level of cortisol showed a significant circadian variation(P<0.001),with higher concentrations observed in the morning compared to the afternoon.Conclusions:This study not only validated the known physiological characteristics of cortisol and progesterone but also provided a detailed description of the age-related trends in androgen levels for the first time.These findings could offer precise time,age,and menstrual cycle references for analyzing the serum steroid hormone levels and diagnostic cut-off value in PCOS patients,which can improve the accuracy of diagnosis.
作者
甄璟然
林斯丽
郁琦
ZHEN Jing-ran;LIN Si-li;YU Qi(Department of Obstetrics&Gynecology,National Clinical Research Center for Obstetric&Gynecologic Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730;Hangzhou BIOZON Medical Co.,Ltd.,Hangzhou 310013)
出处
《生殖医学杂志》
2025年第8期1015-1023,共9页
Journal of Reproductive Medicine
基金
国家卫生健康委医药卫生科技发展研究中心临床科研专项(WKZX2024DN0101)
国家临床重点专科建设项目(U114000)。
关键词
多囊卵巢综合征
类固醇激素
质谱法
参考范围
Polycystic ovary syndrome
Steroid hormones
Mass spectrometry
Reference intervals
