Abstract:
The classical androgens, testosterone and dihydrotestosterone, together with dehydroepiandrosterone, the precusrsor to all androgens, are generally included in diagnostic steroid evaluations of androgen excess and deficiency disorders and monitored in androgen replacement and androgen suppressive therapies. The C11-oxy androgens also contribute to androgen excess disorders and are still often excluded from clinical and research-based steroids analysis. The contribution of the C11-oxy androgens to the androgen pool has not been considered in androgen deficiency. An exploratory investigation into circulating adrenal and gonadal steroid hormones in men was undertaken as neither the classical androgens nor the C11-oxy androgens have been evaluated in the context of concurrent measurement of all adrenal steroid hormones. Serum androgens, mineralocorticoids, glucocorticoids, progesterones and androgens were assessed in 70 healthy young men using ultra high performance supercritical fluid chromatography and tandem mass spectrometry. Testosterone, 24.5 nmol/L was the most prominent androgen detected in all participants while dihydrotestosterone, 1.23 nmol/L, was only detected in 25% of the participants. The 11-oxy androgens were present in most of the participants with 11-hydroxyandrostenedione, 3.37 nmol, in 98.5%, 11-ketoandrostenedione 0.764 in 77%, 11-hydroxytestosterone, 0.567 in 96% and 11-ketotestosterone: 0.440 in 63%. A third of the participants with normal testosterone and comparable 11-ketotestosterone, had significantly lower dehydroepiandrosterone (p < 0.001). In these males 11-hydroxyandrostenedione (p < 0.001), 11-ketoandrostenedione (p < 0.01) and 11-hydroxytestosterone (p < 0.006) were decreased. Glucocorticoids were also lower: cortisol (p < 0.001), corticosterone (p < 0.001), cortisone (p < 0.006) 11-dehydrocorticosterone (p < 0.001) as well as cortisol:cortisone (p < 0.001). The presence of dehydroepiandrosterone was associated with 16-hydroxyprogesterone (p < 0.001), which was also significantly lower. Adrenal and gonadal steroid analysis showed unexpected steroid heterogeneity in normal young men. Testosterone constitutes 78% of the circulating free androgens with the 11-oxy androgens abundantly present in all participants significantly contributing 22%. In addition, a subset of men were identified with low circulating dehydroepiandrosterone who showed altered adrenal steroids with decreased glucocorticoids and decreased C11-oxy androgens. Analysis of the classical and 11-oxy androgens with the additional measurement of dehydroepiandrosterone and 16-hydroxyprogesterone may allow better diagnostic accuracy in androgen excess or deficiency.
摘要:
经典的雄激素,睾酮和二氢睾酮,与脱氢表雄酮一起,所有雄激素的前体,通常包括在雄激素过量和缺乏疾病的诊断类固醇评估中,并在雄激素替代和雄激素抑制疗法中进行监测。C11-氧雄激素也有助于雄激素过量疾病,并且仍然经常被排除在临床和基于研究的类固醇分析之外。在雄激素缺乏中尚未考虑C11-氧雄激素对雄激素库的贡献。对男性循环肾上腺和性腺类固醇激素进行了探索性研究,因为在同时测量所有肾上腺类固醇激素的情况下,既没有评估经典雄激素也没有评估C11-氧雄激素。血清雄激素,盐皮质激素,糖皮质激素,使用超高效超临界流体色谱和串联质谱法对70名健康年轻男性进行了孕激素和雄激素的评估。睾酮,24.5nmol/L是所有参与者中检测到的最突出的雄激素,而二氢睾酮,1.23nmol/L,仅在25%的参与者中检测到。11-氧雄激素存在于大多数具有11-羟基雄烯二酮的参与者中,3.37nmol,98.5%,11-酮雄烯二酮0.764,占77%,11-羟基睾酮,96%的0.567和11-酮雌酮:63%的0.440。三分之一的参与者有正常的睾酮和相当的11-酮雌酮,脱氢表雄酮显著降低(p<0.001)。在这些男性中,11-羟基雄烯二酮(p<0.001),11-酮雄烯二酮(p<0.01)和11-羟基睾酮(p<0.006)降低。糖皮质激素也较低:皮质醇(p<0.001),皮质酮(p<0.001),可的松(p<0.006)11-脱氢皮质酮(p<0.001)以及皮质醇:可的松(p<0.001)。脱氢表雄酮的存在与16-羟基孕酮有关(p<0.001),也明显较低。肾上腺和性腺类固醇分析显示,正常年轻男性中意外的类固醇异质性。睾酮占循环游离雄激素的78%,所有参与者中大量存在的11-氧雄激素显着贡献22%。此外,部分男性患者被确定为低循环脱氢表雄酮患者,其肾上腺类固醇改变,糖皮质激素减少,C11-氧雄激素减少.通过对脱氢表雄酮和16-羟基孕酮的额外测量,对经典和11-氧雄激素的分析可能会提高雄激素过量或缺乏的诊断准确性。