After ALLHAT: doxazosin for the treatment of benign prostatic hyperplasia

Abstract

Doxazosin mesylate is an α1-adrenoceptor antagonist that was used to treat hypertension until a major study (ALLHAT; Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) showed that it increased the risk of progressing to heart failure. Doxazosin is now being used to treat benign prostatic hyperplasia (BPH). Noradrenaline acts on α1-adrenoceptors to contract the smooth muscle in the prostate and bladder, and by opposing these actions, doxazosin is beneficial in BPH. Doxazosin also increases apoptosis in the prostate. Although the standard preparation is suitable for once-daily dosing in BPH, it has to be titrated through three steps to its final dose. The controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin is more convenient to use as it only has to be titrated through one step. In the treatment of BPH, standard doxazosin reduced both obstructive and irritative symptoms and increased peak urinary flow rate. The main side effects with doxazosin are those commonly associated with lowering blood pressure, although doxazosin lowers blood pressure to a lesser extent in normotensives than hypertensives. There is some evidence that in addition to being easier to use, doxazosin GITS may cause less adverse effects than the standard preparations. The benefits of doxazosin and the 5α-reductase inhibitor, finasteride, may be additive in BPH especially in men with large prostates. Further trials are necessary in order to determine whether doxazosin GITS is superior to other α1-adrenoceptor antagonists in BPH.