5a -reductase

Figure 42-6. Dihydrotestosterone is formed from testosterone through action of the enzyme 5a-reductase.

Anti-androgens and hormones 5a-Reductase inhibitors Progesterone and estrogen Recreational drugs Ethanol Cocaine Marijuana... 

Compare and contrast a-adrenergic antagonists versus 5a-reductase inhibitors in terms of mechanism of action, treatment outcomes, adverse effects, and interactions when used for management of benign prostatic hyperplasia. 

The testes and adrenal glands produce 90% and 10%, respectively, of circulating testosterone. Testosterone enters prostate cells, where predominantly type II 5a-reductase activates testosterone to dihydrotestosterone, which combines with a cytoplasmic receptor. The complex enters the nucleus and induces changes in protein synthesis which promote glandular tissue growth of the prostate. Thus, 5a-reductase inhibitors (e.g., finasteride and dutas-teride) directly interfere with one of the major etiologic factors of BPH. 

In an enlarged gland, the epithelial/stromal tissue ratio is 1 5.3 Androgens stimulate epithelial, but not stromal tissue hyperplasia. Hence, androgen antagonism does not induce a complete reduction in prostate size to normal. This explains one of the limitations of the clinical effect of 5a-reductase inhibitors. 

For patients with moderate to severe symptoms, the patient is usually offered drug treatment first. a-Adrenergic antagonists are preferred over 5a-reductase inhibitors because the former have a faster onset of action (days to a few weeks) and improve symptoms independent of prostate size. 5a-reductase inhibitors have a delayed onset of action (i.e., peak effect may... 

TABLE 49-4. Comparison of a-Adrenergic Antagonists and 5a-Reductase Inhibitors for Treatment of Benign Prostatic Hyperplasia47... 

TABLE 49-7. Comparison of Pharmacologic Properties of 5a-Reductase Inhibitors36 48... 

Sub-type inhibition of the 5a-reductase enzyme Percent of inhibition of serum dihydrotestosterone level Percent of patients with reduction in serum dihyrotestosterone Time to peak onset of reduction in serum dihydrotestosterone level Percent inhibition of intraprostatic d i hy d rotestosterone Half-life... 

Drug treatment failures may result from a variety of factors. Initial failure to respond to a-adrenergic antagonists occurs in 20% to 70% of treated patients. It is likely in these patients that the static factor may predominate as the cause of symptoms in these patients. Initial failure to respond to 5a-reductase inhibitors occurs in 30% to 70% of treated patients. 

If the patient is started on a 5a-reductase inhibitor, monitor the patient for drug-induced decreased libido, erectile dysfunction, or ejaculation disorders. If severe, discontinue the drug. 

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