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The Efficacy and Safety of Tamsulosin for the Medical Treatment of Benign Prostate Hyperplasia

Levent Ozdal, MD, Research Fellow, Department of Urology, McGill University, Montreal, QC.
Simon Tanguay, MD, FRCS(C), Associate Professor, Department of Urology, McGill University, Montreal, QC.

Benign prostate hyperplasia (BPH) is the most common benign neoplasm in aging men. Although microscopic evidence of BPH occurs in 80% of men who are at least 80 years old, clinical enlargement of the gland only occurs in half of all men in this age group. Furthermore, symptomatic disease only develops in about half of men with clinically enlarged prostate glands.1

Lower urinary tract symptoms (LUTS) of BPH can be obstructive or irritative in nature. Most symptoms occur and progress slowly in aging men. The treatment of BPH is usually indicated once patients develop either moderate or severe symptoms, or in the presence of complications due to bladder obstruction. Complications of BPH due to chronic obstruction include recurrent urinary tract infection, bladder stones, incontinence, gross hematuria, urinary retention or renal failure.

The aim of BPH treatment should include improving or eradicating symptoms, reversing the complications of the disease and preventing additional sequelae. Treatment is typically based on the severity of symptoms and patient preference.2 Although treatment options include both medical and surgical approaches, medical therapy remains the first-line treatment for most patients with LUTS suggestive of BPH. Medical treatment can be directed at either the static (related to mechanical obstruction by an enlarged prostate) or the dynamic (caused primarily by the smooth muscle tone in the prostatic urethra and bladder neck) components of BPH. Finasteride, a 5-a reductase inhibitor, reduces dihydrotestosterone (DHT) by blocking its conversion from testosterone.3-5 This reduction in DHT provokes a slow decrease in prostate volume affecting the static component of BPH.6 Given that its clinical efficacy is associated with a reduction in prostate size, it is not surprising that finasteride was found to be effective mainly in men with enlarged prostates (= 40 g).7 Furthermore, symptomatic relief is usually noticed only months after initiation of therapy.

The dynamic component of obstruction can be treated with a1-adrenergic antagonists. Three types of a1-adrenergic receptors have been identified. The a1A adrenoreceptors are found predominantly in the prostate, whereas the a1B and a1D receptor subtypes are present in higher concentrations in the smooth muscle of large arteries. The pharmacological effect of this class of medication leads to smooth muscle relaxation within the prostate gland and urethra, resulting in enhanced urinary outflow. These agents are effective in producing symptomatic relief of obstructive voiding in 60-70% of treated patients and increase peak and mean urinary flow rate by 16-25%.2,8

There has recently been an evolution in the availability and use of different a-blockers for the treatment of BPH. Non-selective agents such as phenoxybenzamine were initially used and subsequently replaced by a short-acting a1 blocker (prazosin), by a long-acting a1 blocker (terazosin, doxazocin) and, finally, by the availability of uroselective a1A-adrenergic antagonists such as tamsulosin or alfuzocin (not yet available in Canada).1 The selective a1A-adrenoreceptor antagonists became more popular because of their specificity to the urinary tract, their reduced adverse effects and the simplicity of the dosing regimen.9

The safety and efficacy of tamsulosin were tested in a number of placebo-controlled studies. The extensive evaluation confirmed the ability of tamsulosin to significantly improve both urinary flow rates and symptom scores in the patient population tested. These two measures represent the objective assessment of the efficacy of any therapeutic approach used in patients with BPH. The benefit observed with tamsulosin was not dose-related, as no clinical