11-Ketotestosterone

Laboratory assay overview

11-oxo-androgens are emerging biomarkers for androgen production of adrenal origin. These biomarkers will be useful in disease in men and women and children. Although the presence of androgens with oxygen at the 11 position of the steroid backbone have been known for some time, the clinical utility and prevalence of these androgens have only recently come to light. As has been the case historically, the research has been enhanced with availability of good assay techniques, in this case HPLC MS/MS. 11-ketotestosterone and 11-ketodihydrotestosterone bind the androgen receptor as well as testosterone and DHT.1 The 11-oxo-androgens also follow the same metabolic pathways as androgens without oxygen at 11. Interestingly, the origin of 11-oxo-androgens is entirely adrenal. All of this is important because 11-oxo-androgens appear to play a significant role in some endocrine diseases. PCOS: Polycystic ovary syndrome (PCOS) is a disease characterized by amenorrhea or oligomenorrhea and excess androgens. Although this syndrome is found in 5-10% of women, the disease is not well understood. 11-ketotestosterone has been shown to be in excess in PCOS patients, and levels in those patients are in fact higher than levels of testosterone.3 This finding significantly points to the adrenal as a source of the excess androgens. This idea is supported by the similarity of the levels found in adult men and women. 11-ketotestosterone may be a better biomarker than testosterone or androstenedione for androgen excess in women with PCOS. CAH: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a genetic disease affecting about 1/10,000 people.4 The enzyme defect that causes the disease causes excess adrenal androgen production driven by ACTH, and the major androgens are 11-oxygenated.2 Therefore, 11-oxoandrogens are important to monitor for control of CAH, especially in children and women. In men, 11-oxo-androgens are proposed to be biomarkers for disease activity because they are of adrenal origin. Although excess androgens are a lesser problem for adult men with CAH, these patients are subject to other sequelae of CAH, especially TARTS (testicular adrenal-rest tumors). Following 11-oxo-androgens is expected to be a uniquely useful biomarker since testosterone is not useful as an adrenal androgen for adult men.6 Puberty: Adrenarche is a stage of development that precedes puberty; clinically it is defined by axillary hair and body odor; biochemically it is defined by a rise in adrenal androgens, such as DHEA-sulfate. Testosterone levels do not rise significantly during adrenarche. Recent academic research shows that during adrenarche both DHEA-sulfate and 11-ketotestosterone rise.7 However, DHEA-sulfate is not an active androgen, while 11-ketotestosterone is fully active. Therefore, 11-ketotestosterone may be measured along with DHEA-sulfate when investigating premature adrenarche and premature puberty. Prostate Cancer: The goal of GnRH agonist treatment, antiandrogens and 17-hydroxylase blockade is to minimize androgens in prostate cancer. Eliminating adrenal androgens has been helpful in castration-resistant prostate cancer, and it now appears that 11-ketotestosterone is an important adrenal androgen to control in castration-resistant prostate cancer.1,5 11-ketotestosterone may be an effective adrenal androgen biomarker to monitor in castration-resistant prostate cancer.