Androgens In Health Research Articles

8.20 11-Oxygenated androgens in health and disease

The adrenal gland is the primary source of 11-oxygenated 19-carbon steroids, also termed 11-oxyandrogens, which have several roles in human physiology and disease. These include 11β-hydroxyandrostenedione (11OHA4), 11-Ketotestosterone, (downstream metabolite of 11OHA4, mostly produced in peripheral tissues), and its 5α-reduced product, 11-ketodihydrotestosterone (1). The 11-oxyandrogens are bioactive androgens, with potencies equivalent to those of testosterone and dihydrotestosterone, while concentrations of 11-oxyandrogens are elevated in several disorders of androgen excess (2).

11-Oxygenated androgens in health and disease.

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.

Simultaneous Measurement of Serum Testosterone and Dihydrotestosterone by Liquid Chromatography–Tandem Mass Spectrometry

Recent reports have described inherent problems with androgen immunoassays compared with mass spectrometry analyses. We developed a method for measuring serum testosterone (T) and 5alpha-dihydrotestosterone (DHT) simultaneously via liquid-liquid extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive-mode electrospray ionization. The DHT and T calibrators showed a linear response from 0.069 nmol/L to 34.4 nmol/L and 69.3 nmol/L, respectively. T interference in the DHT assay and vice versa were negligible. Within- and between-run imprecision values were <5% for both analytes. Percent recoveries of T and DHT spiked into samples at concentrations spanning the calibration curve were 100%-113% and 98%-107%, respectively. The lower limit of quantification was 0.069 nmol/L for both steroids. Serum T concentrations measured by LC-MS/MS were different from those obtained by RIA, especially at lower T concentrations. Serum DHT concentrations measured by LC-MS/MS were markedly lower than those generated by RIA because of the nonselectivity of the RIA without chromatography. The reference intervals (mean +/- 2 SDs) determined for T and DHT were 9.2-33.7 nmol/L and 0.47-2.65 nmol/L, respectively, for 113 healthy adult men and 0.33-2.02 nmol/L and 0.09-0.91 nmol/L, respectively, for 133 healthy premenopausal women. We have developed and validated a selective and precise method for simultaneous measurements of serum T and DHT that can be adopted for routine measurements of these androgens in health and disease in men and women.

STUDIES OF THE METABOLISM OF ANDROGENS IN WOMEN1,2

It is most improbable that the presence of male compounds in the female organism is without significance or without effect on the sexual and other organs and functions … It follows that the endocrine treatment of diseases of women cannot be perfecte until 1) the male sexual hormones present in females have been isolated and identified; 2) a thorough experimental investigation of the physiological and pathological properties of these hor′ mones, alone, and in combination with oestrogenic hormones and progesterone, has been carried out; 3) the normal ratio of oestrogenic hormones to progesterone and to male hormones in normal women has been ascertained; 4) the pathological disturbance of this ratio during endocrine and gynecologic disturbances in women has been discovered. A year ago our group began a comprehensive study of the gynecic rOle of androgens in health and in disease.