The adrenal gland is a source of sex steroid precursors, and its activity is particularly relevant during fetal development and adrenarche. Following puberty, the synthesis of androgens by the adrenal gland has been considered of little physiologic importance. Dehydroepiandrosterone (DHEA) and its sulfate, DHEAS, are the major adrenal androgen precursors, but they are biologically inactive. The second most abundant unconjugated androgen produced by the human adrenals is 11β-hydroxyandrostenedione (11OHA4). 11-Ketotestosterone, a downstream metabolite of 11OHA4 (which is mostly produced in peripheral tissues), and its 5α-reduced product, 11-ketodihydrotestosterone, are bioactive androgens, with potencies equivalent to those of testosterone and dihydrotestosterone. These adrenal-derived androgens all share an oxygen atom on carbon 11, so we have collectively termed them 11-oxyandrogens. Over the past decade, these androgens have emerged as major components of several disorders of androgen excess, such as congenital adrenal hyperplasia, premature adrenarche and polycystic ovary syndrome, as well as in androgen-dependent tumours, such as castration-resistant prostate cancer. Moreover, in contrast to the more extensively studied, traditional androgens, circulating concentrations of 11-oxyandrogens do not demonstrate an age-dependent decline. This Review focuses on the rapidly expanding knowledge regarding the implications of 11-oxyandrogens in human physiology and disease.

肾上腺是性类固醇前体的来源，其活性在胎儿发育和肾上腺原位特别重要。青春期后，肾上腺合成雄激素的生理学意义不大。脱氢表雄酮（DHEA）及其硫酸盐DHEAS是主要的肾上腺雄激素前体，但它们在生物学上没有活性。人肾上腺产生的第二丰富的未结合雄激素是11β-羟基雄烯二酮（11OHA4）。11-酮睾酮是11OHA4的下游代谢产物（主要在周围组织中产生），它的5α还原产物11-酮二氢睾酮是具有生物活性的雄激素，其功效与睾丸激素和二氢睾丸激素相当。这些肾上腺衍生的雄激素在碳11上都共享一个氧原子，因此我们将它们统称为11-氧化雄激素。在过去的十年中，这些雄激素已成为多种雄激素过多疾病的主要成分，例如先天性肾上腺皮质增生，肾上腺早衰和多囊卵巢综合征，以及雄激素依赖性肿瘤（例如去势抵抗性前列腺癌）。而且，与更广泛研究的传统雄激素相反，循环中的11-氧基雄激素并未显示出年龄依赖性的下降。这篇评论的重点是关于11-氧雄激素在人类生理和疾病中的意义的迅速增长的知识。肾上腺皮质过早和多囊卵巢综合征，以及雄激素依赖性肿瘤，例如去势抵抗性前列腺癌。而且，与更广泛研究的传统雄激素相反，循环中的11-氧基雄激素并未显示出年龄依赖性的下降。这篇评论的重点是关于11-氧雄激素在人类生理和疾病中的意义的迅速增长的知识。肾上腺皮质过早和多囊卵巢综合征，以及雄激素依赖性肿瘤，例如去势抵抗性前列腺癌。而且，与更广泛研究的传统雄激素相反，循环中的11-氧基雄激素并未显示出年龄依赖性的下降。这篇评论的重点是关于11-氧雄激素在人类生理和疾病中的意义的迅速增长的知识。