Doxazosin in physiologically and pharmacologically normotensive men with benign prostatic hyperplasia.

OBJECTIVES: To compare the effects of doxazosin on blood pressure when used for the treatment of benign prostatic hyperplasia (BPH) in men who are either physiologically or pharmacologically normotensive. METHODS: Sixty-three men with BPH were enrolled in two open-label, parallel, randomized studies. Thirty-one were physiologically normotensive and 32 had hypertension controlled by antihypertensive therapy (pharmacologically normotensive). Of these, 17 were taking calcium channel blockers; 6, angiotensin-converting enzyme inhibitors; and 9, beta blockers. After a 3-week titration period, patients from one study received doxazosin (4 mg/day) for 3 months, given as a single dose in either the morning or evening, and in the second study patients were randomized to receive either 4 mg or 8 mg daily, either in the morning or evening. Effects on blood pressure, maximum uroflow, and the Boyarsky symptom score were measured. RESULTS: Doxazosin produced statistically significant but clinically unimportant reductions in blood pressure in both physiologically and pharmacologically normotensive groups. Statistically and clinically significant improvements in BPH symptoms and maximal perfusion occurred in both groups within 1 month, and further improvements were improved after 3 months. These effects were evident whether doxazosin was administered in the morning or evening. Doxazosin was well tolerated, the only adverse events being dizziness in 5 patients and fatigue in 4. By protocol, all patients reporting adverse events were required to be discontinued from the study. Adverse events did not differ between the groups. There was some indication that patients experiencing adverse events also experienced greater reductions in blood pressure. CONCLUSIONS: Doxazosin may be introduced for the treatment of BPH in hypertensive men whose blood pressure is already controlled by another antihypertensive agent, without a further clinical reduction in blood pressure. It is effective and well tolerated as a once-daily dose given in the morning or evening.

Terazosin and doxazosin in normotensive men with symptomatic prostatism: a pilot study to determine the effect of dosing regimen on efficacy and safety.

In this pilot study, the effect of dosing schedule on the efficacy and safety of the long-acting alpha 1-adrenergic blockers, terazosin (TER) and doxazosin (DOX), was evaluated in 43 consecutive normotensive men (mean age 59.6 years) with symptoms of prostatism. Patients were randomized to one of four treatment groups: (1) TER 5 mg once in the morning (AM; n = 10), (2) TER 5 mg once in the evening (PM; n = 11), (3) DOX 4 mg once AM (n = 11), and (4) DOX 4 mg once PM (n = 11). Patients were titrated to their final dose over 3 weeks. Parameters evaluated included Boyarsky symptom score (Sx), peak uroflow (Qmax), blood pressure and occurrence of adverse events. Once stabilized, patients were seen at 3-month intervals; follow-up ranged from 4 to 17 months (mean 9.7). Clinical improvement as determined by Sx and Qmax was similar for all four treatment groups. Mean decreases in Sx at 3 months were 4.6, 5.4, 4.9, and 5.0 for TER-AM, TER-PM, DOX-AM, and DOX-PM, respectively. Mean peak uroflow increased 3.0, 3.1, 2.8, and 3.1 ml/s for TER-AM, TER-PM, DOX-AM, and DOX-PM, respectively (p < 0.05 vs. baseline). Eight patients (18%) were withdrawn from the study because of adverse events (fatigue 1, asthenia 1, headache 3, dizziness 4): 5 during the titration phase (TER-AM: 2, DOX-AM: 2, TER-PM: 1) and 3 during the treatment phase (TER-AM: 2, DOX-AM: 1). In these 8 patients, the mean decreases in sitting and standing blood pressure were approximately 7/5 and 10/8 mm Hg, respectively. These data suggest that efficacy of TER and DOX was similar at the dosages employed and not affected by the dosing schedule. Adverse events in this small population were significantly decreased (p < 0.05) by dosing in the PM. These preliminary results suggest that a larger prospective study is warranted to determine (1) the comparative efficacy of TER and DOX in the treatment of symptomatic benign prostatic hyperplasia and (2) optimal timing of the medication.

Effect of dosing regimen on efficacy and safety of doxazosin in normotensive men with symptomatic prostatism: a pilot study.

OBJECTIVES: In this pilot study, the effect of dosing schedule on the efficacy and safety of the long-acting alpha 1-adrenergic blocker doxazosin (DOX) was evaluated in 48 consecutive, normotensive men (mean age, 61.2 years) with symptoms of prostatism. METHODS: In this titration to fixed dose study, patients were randomized into 1 of 4 treatment groups: (1) 4 mg DOX once in the AM (n = 12); (2) 4 mg DOX once in the PM (n = 12); (3) 8 mg DOX once in the AM (n = 12); and (4) 8 mg DOX once in the PM (n = 12). Parameters evaluated included Boyarsky symptom score (Sx), peak uroflow (Qmax), blood pressure, and occurrence of side effects. Once stabilized, patients were seen at 3-month intervals; follow-up ranged from 3 to 19 months (mean, 7.7). RESULTS: Clinical improvement as determined by Sx and Qmax was similar for AM and PM groups with either 4 or 8 mg of DOX. Mean decreases in Sx at 3 months were 4.6, 4.2, 5.1, and 5.2 and at 6 months were 4.7, 4.7, 5.3, and 5.4 for the 4 mg AM, 4 mg PM, 8 mg AM, and 8 mg PM, respectively. Mean peak uroflow at 3 months increased 2.7, 2.9, 3.2, and 3.3 mL/s and at 6 months increased 2.6, 3.0, 3.4, and 3.5 mL/s for the 4 mg AM, 4 mg PM, 8 mg AM, and 8 mg PM, respectively (p < 0.05). Six patients (13%) were dropped from the study because of side effects (2 for fatigue, 2 for headache, 2 for dizziness): 5 during the titration phase (4 mg AM: 2; 8 mg AM: 2; 8 mg PM: 1), and 1 during the treatment phase (8 mg AM). CONCLUSIONS: These data suggest that evening dosing does not diminish efficacy yet may enhance toleration of DOX. These preliminary results suggest that a larger prospective study is warranted to determine the optimal dosing and timing of DOX in the management of symptomatic benign prostatic hyperplasia.

Transrectal hyperthermia in the management of men with prostatism: an algorithm for therapy.

Transrectal hyperthermia has been proposed as a potential treatment for benign prostatic hyperplasia (BPH). This report presents our initial experience in an ongoing clinical trial to evaluate the safety and efficacy of transrectal thermal therapy (TRTT) for symptomatic BPH. To date, 24 patients (mean age 60.6 years) have undergone TRTT. In all cases the initial investigations included pre-operative symptom score analysis, synchronous video/pressure/flow urodynamic studies and transrectal measurement of both the size of the prostate and the distance between the applicator and the prostatic urethra (AU). Twenty-one patients completed the study (mean follow-up 6.7 months). There was a significant reduction in symptom score (> 50%) in 14 patients and the peak urinary flow rate (Qmax) increased from 5.9 to 12.4 ml/s at 1 month, 12.7 ml/s at 3 months and 13.2 ml/s at 6 months. In 12 patients the decrease in symptom score and the increase in flow rate exceeded 50%. Five of the 6 patients who failed to respond to treatment had prostate volumes > 85 g; 4 had voiding detrusor pressures < 40 cm H2O and 5 had an AU distance > 2.5 cm. These preliminary results suggest that TRTT may be a potential therapeutic alternative in patients with mild to moderate symptoms of prostatism. However, patients with either lower detrusor pressures (< 40 cm H2O) or very large prostates are unlikely to show a beneficial response. We suggest that large prostates may preclude effective temperature distribution and therefore mitigate the potential therapeutic benefit.

Prostatic and periprostatic interstitial temperature measurements in patients treated with transrectal thermal therapy (local intracavitary microwave hyperthermia).

One of the questions raised regarding the use of transrectal thermal therapy in the treatment of benign prostatic hyperplasia (BPH) is whether there is a uniform and safe temperature distribution within the prostate. Our study represents the first attempt in humans to map the interstitial thermal distribution in the prostate during transrectal thermal therapy. With the patient under local anesthesia and under ultrasound guidance, a transperineal 3-point thermocouple was placed into various areas of the prostate in 15 patients. Prostatic-urethral thermocouple distance ranged from 1 to 3 cm. A urethral catheter containing a 5-point linear array thermocouple was placed and the balloon was inflated so that the proximal point was at the bladder neck and the remaining points were at 1 cm. intervals along the prostatic urethra. Power (25 watts) was delivered via the Primus (Technomatix) transrectal microwave applicator with simultaneous cooling of the rectal mucosa (between 12 and 14C). Treatment was delivered for 60 minutes and temperatures were recorded. In the prostatic substance a maximal temperature of 45C was observed during the heat-up phase and this decreased as the vasoactive response occurred. Temperature along the prostatic urethra varied between 40 and 43C and never exceeded 44C. A similar distribution of temperature was registered in the thermocouple points in the prostatic substance. The anticipated thermal dose of 41.5 +/- 1C for 60 minutes was achieved in the prostatic substance as measured by the sensors in the prostatic urethra and interstitial sensors. The results suggest that transrectal thermal therapy delivers a uniform and safe distribution of heat in the prostatic substance and urethra. Clinical trials are currently underway to ascertain the efficacy of transrectal thermal therapy in the management of BPH.