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采用高特异性液相色谱-串联质谱法测定的内源性类固醇与 70 岁男女的常见心血管疾病。

Endogenous steroids measured by high-specificity liquid chromatography-tandem mass spectrometry and prevalent cardiovascular disease in 70-year-old men and women.

机构信息

Department of Women's and Children's Health, Section for Obstetrics and Gynecology, University Hospital, Uppsala SE-751 85, Sweden.

出版信息

J Clin Endocrinol Metab. 2010 Apr;95(4):1889-97. doi: 10.1210/jc.2009-1722. Epub 2010 Feb 17.

DOI:10.1210/jc.2009-1722
PMID:20164295
Abstract

CONTEXT

There is a need for increased knowledge about endogenous sex hormone levels and clinical outcomes of risk/benefit. Immunoassays have poor specificity to reliably measure low steroid concentrations in elderly.

OBJECTIVE

The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry.

SETTING

The study was conducted at a university hospital research unit.

DESIGN AND METHODS

Plasma samples were analyzed from 202 70-yr-olds as part of a large population-based study, Prospective Investigation of the Vasculature in Uppsala Seniors. Twenty-eight of these had prevalent CVD. Eleven steroids were quantified, using liquid chromatography-tandem mass spectrometry. Women with current/previous menopausal hormone therapy (n = 35) were excluded.

RESULTS

Men without prevalent CVD had higher plasma 17beta-estradiol (E2), compared with women. Men with prevalent CVD, compared with those without, had lower 17-hydroxypregnenolone (17OHPregn), 17-hydroxyprogesterone, and higher estrone/androstenedione and E2/testosterone (T) (aromatase activity). Women with prevalent CVD had lower pregnenolone, 17OHPregn, and dehydroepiandrosterone (DHEA) but higher DHEA/17OHPregn, androstenedione/DHEA, E2/T, E2/estrone, and E2/SHBG. The aromatase index, E2/T, was higher for prevalent CVD in both sexes. Adjustment for statin use, smoking, and body mass index yielded additional significant differences in men, whereas some were lost in women. Logistic regression indicated strong associations between prevalent CVD and low 17OHPregn, adjusted odds ratio of 0.18, 95% confidence interval (0.06-0.61); P = 0.006, in women and low 17-hydroxyprogesterone, 0.45 (0.25-0.80); P = 0.007 in men, most likely caused by increased throughput (consumption) toward estrogen synthesis.

CONCLUSIONS

Prevalent CVD was associated with indications of lower androgen precursors, increased aromatase activity, and higher estrogen levels in both sexes. Results might represent an endogenous response to a condition of developing atherosclerosis, rather than a causative relationship. Furthermore studies are needed.

摘要

背景

需要更多地了解内源性性激素水平和风险/获益的临床结果。免疫测定法特异性差,无法可靠地测量老年人的低类固醇浓度。

目的

本研究旨在使用质谱法评估与老年人群中心血管疾病(CVD)相关的血浆类固醇浓度。

设置

该研究在大学医院研究单位进行。

设计和方法

作为一项大型基于人群的研究的一部分,从 202 名 70 岁的老年人中分析了血浆样本,该研究为乌普萨拉老年人血管前瞻性研究。其中 28 名患有常见 CVD。使用液相色谱-串联质谱法定量了 11 种类固醇。排除了当前/以前接受过激素替代疗法的女性(n=35)。

结果

没有常见 CVD 的男性的血浆 17β-雌二醇(E2)水平高于女性。与没有常见 CVD 的男性相比,患有常见 CVD 的男性的 17-羟孕烯醇酮(17OHPregn)、17-羟孕酮和更高的雌酮/雄烯二酮和 E2/睾丸酮(T)(芳香酶活性)较低。患有常见 CVD 的女性的孕烯醇酮、17OHPregn 和脱氢表雄酮(DHEA)水平较低,但 DHEA/17OHPregn、雄烯二酮/DHEA、E2/T、E2/雌酮和 E2/SHBG 水平较高。两性的常见 CVD 均与芳香酶指数(E2/T)升高有关。调整他汀类药物使用、吸烟和体重指数后,男性有更多显著差异,而女性则有些差异消失。逻辑回归表明,常见 CVD 与低水平的 17OHPregn 密切相关,调整后的优势比为 0.18(95%置信区间为 0.06-0.61);P=0.006,女性低水平的 17-羟孕酮,0.45(0.25-0.80);P=0.007,可能是由于雌激素合成的通量(消耗)增加所致。

结论

在两性中,常见 CVD 与雄激素前体水平降低、芳香酶活性增加和雌激素水平升高有关。结果可能代表了正在发生动脉粥样硬化的条件下的内源性反应,而不是因果关系。此外,还需要进一步的研究。

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