Inhibitors of 5alpha-reductase in the treatment of benign prostatic hyperplasia

Abstract

The description of 5alpha-reductase deficiency in male pseudohermaphroditism, characterization of type-1 and type-2 isoenzymes of 5alpha-reductase, and development of 4-aza steroid competitive inhibitors of 5alpha-reductase were milestones in the development of 5alpha-reductase inhibitors, a class of drugs approved for the treatment of symptomatic benign prostatic hyperplasia (BPH). Stromal and epithelial hyperplasia in the region of the prostate that surrounds the urethra begins in the fourth decade of life and by the sixth decade, the prevalence is 50%. Benign prostatic hyperplasia is a frequent cause of lower urinary tract symptoms, urinary tract infection, and acute urinary retention requiring surgical intervention. Medical options for treatment of symptomatic BPH include 1) the 5alpha-reductase inhibitors finasteride and dutasteride, 2) the alpha1-adrenergic antagonists doxazocin, terazosin, tamsulosin, and alfuzosin, and 3) the combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist. By inhibiting the production of dihydrotestosterone (DHT) locally within the prostate gland, 5alpha-reductase inhibitors have the effect of reducing prostate volume, improving lower urinary tract symptoms, increasing peak urinary flow, and decreasing the risk of acute urinary retention and need for surgical intervention. Alpha-1 adrenergic antagonists relax the smooth muscle of the bladder neck and prostate, thereby decreasing the resistance to urine flow and increasing peak urinary flow and improving lower urinary tract symptoms. The alpha1-adrenergic antagonists are effective in the short-term, and reduce clinical progression of BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. The 5alpha-reductase inhibitors are effective in the long-term, especially in men with large prostates, and reduce the clinical progression of BPH, and further reduce the long-term risk of urinary retention and need for surgical intervention. The combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist significantly reduces the clinical progression of BPH over either drug class alone.