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.