Androgens, Urinary

ANDROGEN HORMONE INHIBITOR The nurse questions the patient at length about symptoms of BPH, such as frequency of voiding during the day and night and difficulty starting tire urinary stream. The nurse records all symptoms in the patient s chart. 

The adult male prostate contains abundant acid phosphatase which it secretes into the semen. The production of this enzyme is governed by the circulating levels of androgenic hormones. Castration or estrogen administration markedly reduces the prostatic urinary acid phosphatase of males. Other organs such as the liver, kidney, spleen, red cells and platelets also contain significant amounts of acid phosphatase. 

In males the androgens arise predominantly from the testes which are said to vary from 10 to 45 gm. in weight.2 Actually eunuchoid individuals may have testes weighing as little as 1 or even 1/2 gm. for the pair. In this case as well as many others the dividing line between normal and abnormal is difficult to draw. No dependable data are available as to the inter-individual ranges of concentration of androgens in human blood. Urinary excretion has been studied, however, and ranges for normal men have been reported up to 11-fold, i.e., 20... 

Juricskay S, Telegdy E. 2000. Urinary steroids in women with androgenic alopecia. Clin Biochem 33 97. 

Dehennin L, Ferry M, Lafarge P, Peres G, Lafarge J-P. 1998. Oral administration of dehydroepiandrosterone to healthy men alteration of the urinary androgen profile and consequences for the detection of abuse in sport by gas chro-matography-mass spectrometry. Steroids 63 80-87. 

The catabolism of plasma testosterone and other androgens occurs primarily in the liver (Fig. 63.3), where they are conjugated into water-soluble compounds that are excreted by the kidney as the urinary 17-ketosteroids. 

Finrozole is a nonsteroidal competitive aromatase inhibitor that is being evaluated in Phase II trials for the treatment of lower urinary tract symptoms associated with a reduced androgen/estrogen ratio in aging males associated with BPH. 

Most of the synthetic androgens and anabolic agents are 17-alkyl-substituted steroids. Administration of drugs with this structure is often associated with evidence of hepatic dysfunction. Hepatic dysfunction usually occurs early in the course of treatment, and the degree is proportionate to the dose. Bilirubin levels may increase until clinical jaundice is apparent. The cholestatic jaundice is reversible upon cessation of therapy, and permanent changes do not occur. In older males, prostatic hyperplasia may develop, causing urinary retention. 

The synthesis of adrenal steroids is illustrated in Fig. 5.3.1. Cortisol, corticosterone, and aldosterone are formed by sequential hydroxylations and oxidoreductions from pregnenolone and progesterone. 17a-Hydroxypregnenolone (17HP) is a branchpoint constituent because it can be converted to cortisol or adrenal androgens. All of the components of this pathway can be quantified by MS/MS. The steroids around the periphery are urinary metabolites and these are measured by GC-MS following hydrolysis of conjugates and derivatization. 

We studied by GC-MS the urinary excretion of a single patient with a documented mutation [49] and have found that the 5/3-reduced androgen metabolite excretion relative to 5a is decreased by about 80%, and 5/ -corticosteroid metabolite excretion is essentially absent [63]. To date there has no report of an adverse endocrine phenotype related to corticosteroid, mineralocorticoid, or androgen metabolism. 

Measurements of urinary unconjugated F and E (UFF and UFE) are not useful for accurate diagnosis of ACRD as the ratio between them is typically normal. Patients with ACRD will have elevated levels of androgens, DHEA, testosterone and andro-stenedione. 

A female-specific 15(3 hydroxylase acts on steroid sulfates such as corticosterone sulfate and forms the major urinary excretion product of that hormone in female rats.292 These sex-specific differences in enzymes are thought to be related to secretions of growth hormone that are in turn controlled by the "programming" of the hypothalamus by androgen during the neonatal period in rats272 or during human fetal development. 

One of the side effects of testosterone compounds is masculinization in women (such as hirsutism, acne, depression of menses, and clitoral enlargement) and of their female offspring. Therefore, androgens are contraindicated in pregnant women. Prostatic hypertrophy may occur in males, which leads to urinary retention. Therefore, androgens are contraindicated in men with prostatic carcinoma. 

The liver of several species of inbred rats has provided a novel experimental system for studying the mechanism of action of androgens. The protein, a-2u-globu-lin, constitutes 50% of the urinary protein in male rats and its specific mRNA represents a remarkable 2% of the total hepatic mRNA the protein is virtually undetectable in female rats. In response to androgens, male rats synthesize a unique... 

G03BA Androgens 3-oxoandrosten (4) derivatives (testosterone, methyltestosterone) G Cenito Urinary System and Sex Hormones 481... 

The aim is to remove the fluid gradually with a maximum weight loss of 0.5 kg/day in the absence of peripheral oedema, or 1.0 kg/day if peripheral oedema is present. Too rapid a diuresis will result in intravascular fluid loss rather than the peripheral oedema. The diuretic should be stopped if the serum sodium falls below 120 mmol/L or if there is a rising serum creatinine. Urinary electrolytes should be monitored to ensure that the spironolactone therapy is effective. The aim is to reverse the sodium/potassium ratio in the urine so that more sodium than potassium is excreted. Most frequent side-effects of spironolactone are those related to its anti-androgenic activity, such as decreased libido, impotence and gynaecomastia in men and menstrual irregularities in women. Other side-effects include hyperkalaemia, uraemia, hyponatraemia and nausea. 

Overall, other adrenal androgens also show a progressive decrease in urinary excretion in both men and women. Thus, the mean 17-ketosteroid urine levels of elderly people are about 50% of those in young adults. This is primarily secondary to decreased dehydroepiandrosterone (DHEA) and androsterone production. In men, about one-third of the daily 17-ketosteroids are of testicular origen, the remainder being mainly from the adrenals. Androstenedione is a prehormone for testosterone. 

The bulk of the urinary 17-KSs consists of andro-sterone, epiandrosterone, etiocholanolone, DHEA, 11-keto-and lip-hydroxyandrosterone, and 11-keto- and 11(3-hydroxyetiocholanolone. DHEA and 11-oxygenated 17-KSs are produced only by the adrenal glands, whereas the others also arise from precursors (androstenedione and testosterone) elaborated by the gonads. Thus the main purpose of measuring these steroid metabolites is to assess adrenal androgen production. 

The adrenal cortex, the zona reticularis in particular, daily secretes substantial amounts of DHEA and DHEAS, equaling or exceeding the amount of cortisol. Table 32-1 shows approximate blood levels of the important corticosteroids. Most of the DHEA and all of the DHEAS come from the adrenals. Negligible amounts of testosterone, dihydrotestosterone (DHT), and estradiol are secreted by the cortex however, DHEA and, to a lesser extent, DHEAS undergo conversion to estradiol in skeletal muscle and adipose tissue they also can be converted to testosterone. The adrenal cortex accounts for about two-thirds of the urinary 17-ketosteroids, which are a measure of androgen production. This steroidogenic versatility makes the adrenal cortex an important factor in certain disease states (see below). 

---