0022-5347/95/1541-0110$03.

00/0
THEJOLWALOF UROLOGY
Copyright 0 1995 by AMERICANUROLOCICAL
ASSOCLATIOS, I S C .

Vol. 154, 110-115. July 1995

Printed in U S A

DOXAZOSIN FOR THE TREATMENT OF BENIGN PROSTATIC

HYPERPLASIA IN PATIENTS WITH MILD TO MODERATE ESSENTIAL
HYPERTENSION: A DOUBLE-BLIND, PLACEBO-CONTROLLED,
DOSE-RESPONSE MULTICENTER STUDY
JAY Y. GILLENWATER, RICHARD L. CONN, STEVEN G. CHRYSANT, JOHNNY ROY,
MICHAEL GAFFNEY, KATHLEEN ICE AND NORMA DIAS FOR THE MULTICENTER STUDY GROUP*
From the Departments of Urology, University of Virginia Medical School, Charlottesville, Virginia, Lovelace Scientific Resources Inc.,
Albuquerque. New Mexico, Oklahoma Cardiovascular and Hypertension Center and University of Oklahoma, Oklahoma City, Oklahoma,
and Pfizer Central Research, New York, New York

ABSTRACT

A total of 248 hypertensive patients 45 years old or older with benign prostatic hyperplasia
(BPH) was included in this 18week, multicenter, double-blind, placebo-controlled, parallel-group
dose-response study. Doxazosin, a selective al-adrenoceptor antagonist, produced a significant
increase in maximum urinary flow rate (2.3 to 3.6 ml. per second) a t doses of 4 mg., 8 mg. and 12
mg., and in average flow rate (8 mg. and 12 mg.) compared with placebo. The increase in
maximum flow rate was significant with doxazosin versus placebo within 1 week of initiating
double-blind therapy. Doxazosin compared to placebo significantly decreased patient-assessed
total,obstructive and irritative BPH symptoms. Blood pressure was significantly lower with all
doxazosin doses compared with placebo. Adverse events, primarily mild to moderate in severity,
were reported in 48% of patients on doxazosin and 35% on placebo. Our results strongly support
the use of doxazosin a s a nonoperative therapeutic alternative in the management of uncomplicated BPH. Doxazosin would also be particularly useful in the management of patients who have
BPH and hypertension.
KEY WORDS:prostatic hypertrophy, hypertension, doxazosin, prostatic diseases

Benign prostatic hyperplasia (BPH) occurs in approximately 50%of men 51 to 60 years old and in 90% of men by
the ninth decade.' The symptoms of BPH are believed to be
due to bladder outflow obstruction, which has a mechanical
component associated with enlargement of the prostate gland
and a dynamic component caused by contraction of smooth
muscle in the prostatic stroma, prostatic capsule and bladder
neck. The degree of muscle tone in these areas is regulated
partly by al-adrenergic receptors. Caine et a1 first demonstrated that al-adrenergic receptors are present in prostatic tissue and in the prostate c a p s ~ l e . Furuya
~ . ~ et a14 and
Christensen and Bruskewitzs demonstrated, with the use of
a-adrenergic agonists, a-adrenergic antagonists and spinal
anesthesia, that 40% of the cases of obstruction from BPH
are due to a dynamic component, which has the potential of
being treated by a-adrenergic blockade.
Phenoxybenzamine, a nonselective antagonist of the a1
and a2-adrenergic receptors, was one of the first a-blockers
to be used successfully in the treatment of BPH.6 The effectiveness of this drug, however, is limited by the incidence and
seventy of adverse reactions that occur with its use. BPH
symptomatology has also been effectively managed with selective al-adrenergic antagonists, such as prazosin,? terazosins and alfuzosinp which produce fewer and better tolerated
side effects than phenoxybenzamine.

Doxazosin is a highly selective antagonist of all al-adrenergic receptor subtypes, which include the a l A (cloned 1C)
receptor believed to be the predominant subtype in the prostate.10 Recently, doxazosin was indicated to be safe and efficacious in the treatment of BPH.11 In addition, doxazosin h a
demonstrated excellent efficacy and tolerance in the management of essential hypertension in a wide variety of patients.
The vascular al-adrenergic receptor has a role in the increased peripheral vascular resistance associated with hypertension.12 Thus, doxazosin would be particularly useful in
men with BPH and hypertension. Other advantages of doxazosin are that its effects are not influenced by patient age or
renal function,13 and its long plasma half-life (22 hours)
allows for once daily dosing.14 We determine the efficacy and
safety of doxazosin, administered once daily, for the treatment of BPH in men with mild to moderate essential hypertension.
MATERIALS AND METHODS

Patients. We studied 248 patients 45 years old or older with

BPH and mild to moderate essential hypertension. During 2
consecutive baseline weeks all eligible patients had a maximum urinary flow rate of 5 to 15 ml. per second in a voided
volume of 150 to 500 ml., post-void residual volume of less
than 200 ml., daytime micturition frequency of 4 or more,
nocturia of more than 2 times per night and a sitting diastolic
Accepted for publication December 12, 1994.
* Multicenter Study Group: T. W. A v e s and J. W. Wescott, Day- blood pressure of 90 to 114 mm. Hg. Written informed contona Beach, Florida; S. G. Ch sant and J. Roy, Oklahoma Cit
sent was obtained from all participants.
Oklahoma; A. T. K. Cockett, &Tester and S. A. Kaplan. New Yo&
Patients with any other conditions causing urinary sympNew York R. L. Conn, Albuquerque, New Mexico; R. J. Correa,
Seattle, Washington; A. Fawzy, New Orleans, Louisiana; S. D. toms or decreased flow rate, previous or imminent prostatic
Graham, Atlanta, Georgia; J. A Heaney, Hanover, New Hampshire; surgery, prostate specific antigen level greater than 10 ngJ
J. L. Holtzman, Minnea lis and R. R. Moyer, Hibbing, Minnesota; ml., acute urinary retention, recent catheterization for outJ. S. Isen, Worcester ans"G. P. Lewis, New Bedford, Massachusetts;
P. G . Katz, Richmond, Virginia; G. H. Malek, Madison, Wisconsin; flow obstruction or prostate malignancy were excluded from
and J. D. McConnell, Dallas and I. M. Thompson, Fort Sam Houston, the study. Patients with insulin-dependent or poorly conTexas.
trolled noninsulin-dependent diabetes; significant hepatic,
110

DOXAZOSIN FOR BENIGN PROSTATIC HYPERPLASIA AND HYPERTENSION

renal or cardiovascular dysfunction; secondary hypertension;

concurrent serious disease or malignancy, or significant psychiatric disorders were also excluded. Other reasons for exclusion were intolerancdsensitivity to quinazoline derivatives, substance abuse, recent blood donation, obesity,
antihypertensive drug therapy or any treatment known to
affect vesicourethral function, and recent therapy with any
other investigational drug or any prior doxazosin therapy.
Study design. This prospective, 16-week, double-blind, placebo-controlled, parallel-group, dose-response study was conducted a t 19 centers in the United States. A 0 to 4-week
screening period allowed for the discontinuation and washout of excluded medication, including any other antihypertensive agents. After screening, patients entered a 2-week,
placebo run-in phase (baseline). Patients were then randomized to receive either placebo or doxazosin (2 mg., 4 mg., 8 mg.
or 12 mg. once daily in the morning) for 14 weeks. The initial
dose of doxazosin was 1 mg., increasing sequentially at
weekly intervals during a 5-week titration phase to the randomized, fixed dose level. The dose then remained constant
during the 9-week efficacy phase of the study.
Assessments. The initial screening assessments included a
medical history and physical examination, electrocardiogram
and clinical laboratory evaluations. Blood pressure and heart
rate were measured with the patient in the sitting and standing positions. Urodynamic measurements were made using a
Dantec Urodyn 1000 flowmeter (maximum urinary flow rate,
average urinary flow rate and voided volume) and a Diagnostic Ultrasound Bladder Scan BVI 2000 unit (post-void residual volume). Patients assessed the severity and bothersomeness of BPH symptoms with a modified questionnaire
developed from the 9-symptom index of Boyarsky et all5 by
incorporating each symptom into a severity and bothersomeness question. Table 1 specifies the rating scale used to
assess each symptom.
Patients were evaluated for the efficacy and safety of doxazosin at the end of each week of the placebo run-inand dose
titration periods, and at 4-week intervals during the stable
dose efficacy phase. For efficacy, urinary flow rates, residual
volume, blood pressure and heart rate were assessed approximately 24 hours following the previous morning dose of
study medication (trough) and at 2 to 6 hours following
administration of medication at the clinic (peak).The symp
tom questionnaire was completed at each visit. Patients also
recorded each daytime and nighttime micturition in a daily
diary. BPH symptomatology was also evaluated by the investigator.
Safety was monitored by recording adverse experiences.
Clinical laboratory evaluations were performed at the end of
the placebo run-in phase and at the end of the efficacy phase
or at the time of discontinuation. A physical examination and

111

electrocardiography were conducted a t the final visit. At each

visit patients were asked to report any concomitant medication use. Study drug compliance was assessed by a tablet
count of returned medication.
Analysis of data and statistical methods. The baseline
value for all trough efficacy variables was the mean of the 2
measurements obtained during each week of the a-wek,
placebo run-in period. The scoring of the modified Boymky
symptom questionnaire was reversed so that lower scores
indicated improvement, as with other commonly used symptom scales. The baseline value for the peak d y n a m i c and
blood pressure measuremente was the value obtained at the
end of baseline week 1, since week 2 peak measurements
were obtained after the administration of double-blind medication. The changes from the baseline measurement to the
mean measurement obtained during the stable dose, efficacy
phase (mean analysis), as well as the change to the final
treatment visit (end point analysis) were analyzed. Analysis
of covariance was used and the treatment effect was tested
for signdicance after adjusting for the baseline effect. Pairwise comparisons between treatment groups of the adjusted
mean changes were ale0 conducted.
RESULTS

Of the 248 patients randomized to double-blind treatment

(199 to doxazosin and 49 to placebo) 216 were eligible for the
efficacy analysis (39were randomized to a doxazosin dose of
2 mg., 46 to 4 mg., 45 to 8 mg., 45 to 12 mg. and 41 to placebo).
A total of 7 patients did not have any followup efficacy measurements and 25 did not meet the inclusion criterion for
maximum urinary flow rate. All patients who received doubleblind medication were evaluated for safety.
The treatment groups were well matched for demographic
characteristics, duration of BPH and duration of hypertension (table 2). No significant differences existed between the
treatment groups at baseline in maximum or average urinary flow rates, BPH symptoms, patient diary data, blood
pressure and heart rate. A total of 161 patients (130 given
doxazosin and 31 given placebo) completed the study. Reaso118for patient withdrawal (percent doxazosin patients versus percent placebo patients) included adverse events (11%
versus 4%). lack of blood pressure efficacy (7% versus 12%),
lack of BPH efficacy (0% versus 4%) and protocol violations
(9% versus 10%).
E m . For all efficacy parameters the results of the end
point and mean analyses were similar, thus leading to the
same conclusions. For urinary flow rates the results of the
mean analysis of the efficacy visits are discussed, since this
analysis decreases the variability of single-time measurements that are used in the end point analysis. Results fmm
the end point analysis are presented for patient symptoms
TABLE1. Rating system for symptoms evalwted with the modifid (modified Boyarsky questionnaire), since the questionnaire
allowed patients to assess changes in symptoms with time
Bovarskv auestionnnim
between the end point visit and the previous visit.
Rating
- Scale
At trough doxazosin plasma concentrations the maximum
Symptoms
Severe
Bothersome
flow rate increased significantly by 2.6 to 2.8 ml. per second
in the 8 mg. and 12 mg. doxazosin groups, compared with 0.5
Obstructive:
ml. per Becond in the placebo group (fig. 1).Average flow rate
lto5
lto5
Hesitancy
lto5
lto5
also increased significantly by 1.3 to 1.5 ml. per second in the
Intermittency
lto5
lto5
Dribbling
8 mg. and 12 mg. doxazosin groups, compared with 0.2 ml.
It05
lto3
Impaired stream
per second in the placebo group. No significant differences
Incomplete emptying
were noted between the 8 mg.and 12 mg. groups.
5 to 25
5 to 23
Obstructive subtotal
At peak doxazosin plasma concentrations the maximum
Irritative:
lto5
OW3
Noctutia
flow rate increased significantly in the 4 mg.,8 mg. and 12
lto5
Oto3
Daytime frequency
mg. doxazosin groups by 2.3 to 3.6 ml. per second compared
lto5
lto5
Urgency
an increase of 0.1 ml. per second in the placebo group
with
Burning sensation
(fig. 1).Average flow rate increased significantly by 1.6 to 2.1
4to20
2 to 16
Irritative mubtotal
ml. per second in the 8 mg. and 12 mg. doxazosin groups,
9to45
Total symptom
7 to 39
compared with 0.2 ml. per second in the placebo group. The
Lower wres indicate lesa severejbOtheraOmesymptoms.

DOXAZOSIN FOR BENIGN PROSTATIC HYF'ERPLASIA AND HYPERTENSION

112

TABLE2. Demographic characteristics

Doxazosin (mg.)
Placebo

No. pts.
Age (yrs.1

Wt. (pounds)
BPH duration (yrs.)
Hypertension duration (yrs.)
Mean plus or minus standard deviation.

49
64.5 t 7.7
187 2 26
5.2 ? 4.2
7.6 2 7.0

12

47
64.8 ? 8.5
189 2 28
5.4 z 6.0
10.0 z 7.5

52
64.42 7.5
196 C 29
5.5 ? 5.6
10.6t 8.4

50
63.9 2 8.4
187 2 23
5.9 ? 6.0
10.5 ? 8.5

50
62.8? 8.9
199 ? 28
4.0 2 3.2
10.22 8.5

MEANCHANGE m MAXIMUM

m w RATE

3
2

2MG

BMG

4MG

MEAN CHANGE

12MG

m AVERAGE m w RATE

2
15
1

05

WO

2MG

4MG

0 TROUGH

l2MG

PUK

rmxmsrn
1)Mean w

e adjusted f a haJelii dlect: PBo=Pl&.

'('3 S i @ d y

differen from placebo mean change p

< 0.05 (0.01)

FIG. 1. Mean change from baseline' in urinary flow rate (ml. per second) minus mean analysis

differences between the 8 mg. and 12 mg. groups were not

significant.
A significant increase in maximum urinary flow rate with
doxazosin compared to placebo (p = 0.023) was noted at
trough aRer 1 week of double-blind treatment. At this time
the doxazosin-treated dose groups had received the 1 mg.
dose for 1 week. The change in maximum urinary flow rate
from baseline was a n increase of 0.8 ml. per second with
doxazosin, compared with a decrease of 0.5 ml. per second
with placebo.
The proportion of patients with a 3 ml. per second or greater
increase in maximum flow rate was significantly larger in the 8
mg. and 12 mg. doKazosin groups, compared with placebo at
trough (37% and 39% compared with 13%, respectively) and
peak (42% and 51% compared with 17%, respectively) times
(fig. 2).Although the proportion of patients responding in the
2 mg. and 4 mg. groups was not significantly different from
the placebo group, a change in maximum flow rate of at least
3 ml. per second was noted in 10 to 30% and 32 to 34% of
the patients a t trough and peak, respectively. No significant
differences were noted for voided urine volume or post-void
residual volume for doxazosin compared to placebo.
Doxazosin compared to placebo also significantly improved
patient-assessed BPH symptoms (BPH symptom questionnaire). In the end point analysis of symptoms, 4 mg. doxazosin was superior to placebo for improvement in the seventy

and bothersomeness of total and obstructive symptoms, and

for the severity of irritative symptoms. The seventy of total
and obstructive symptoms also improved significantly with 8
mg. doxazosin (table 3).
Systolic and diastolic blood pressures, with the patient
sitting and standing, were clinically and statistically significantly decreased by 4 mg., 8 mg. (diastolic only) and 12 mg.
doxazosin at trough plasma concentrations compared with
placebo (fig. 3). Sitting blood pressure (systoliddiastolic) at
peak was significantly reduced by 9.1 to 16.119.6to 11.7 mm.
Hg with 2 to 12 mg. doxazosin, compared with reductions of
2.3/4.5 mm. Hg with placebo. Similarly, standing blood pressure was significantly decreased by 11.6 to 17.4/9.8 to 12.7
mm. Hg with 2 to 12 mg. doxazosin compared to a 3.d4.3 mm.
Hg decrease with placebo. Changes in heart rate were slight
and comparable in both treatment groups.
Safety. All 199 doxazosin-treated and 49 placebo-randomized patients were evaluated for safety and all adverse
events, whether believed to be treatment-related or not, were
reported. Overall, adverse events were reported by 48% of
patients given doxazosin and 35% given placebo. The adverse
events most frequently reported in all treatment groups wem
dizziness, headache and fatigue, with headache occurring
more often in the placebo group (table 4). Only 5 of the 199
doxazosin patients (2.5%) experienced hypotension. In OUT
opinion, most adverse events were mild or moderate i n 88.

DOXAZOSIN FOR BENIGN PROSTATIC HYPERPLASIA AND HYPERTENSION

113

60 I

96 Of Patients
With a L 3mllsec
Increase

1;.

50
40
30
20
10

n
PBO

2MG

4MG

8MG

12MG

0TROUGH Ill PEAK

PBO=Placebo; ~ ~ 0 . 0pc0.01
5,
compared with placebo
FIG. 2. Percentage of patients with 3 ml. per second or more increase in maximum urinary flow rate
TABLE3. BPH symptom questionnaire (modifid Boyarsky) and mean change t?om baseline
End Point Analysis of Severity
Placebo
2

No.pts.
Total:*

37

End Point Analysis of Bothersomenesa

Doxazosin (mg.)

34

4
38

8
42

12
39

Placebo
37

34

4
38

8
42

12
39

Baseline mean 28.0 -C 5.0

28.2 ? 3.6 30.0 t 4.6
30.0 t 4.0
29.0 -C 4.6
36.3 ? 6.5
37.1 2 5.8 38.1 ? 5.8
37.4 t 6.6
37.4 t 5.6
Mean changet
-3.0
-3.4
-5.39
-4.7
-4.9
-0.25
-2.8
-5.0$
-4.2%
-3.6
Obstructive:*
Baseline mean 17.1 t 3.7
17.1 -t 3.1 18.5 ? 3.6
1 8 . 6 t 3.0
17.9 t 3.6
20.4 t 3.8
20.6 t 3.5 21.5 t 3.5
21.2 -t 4.2
20.9 2 3.8
Mean changet
-1.8
-2.0
-1.4
-1.8
-3.2$
-2.9%
-2.4
-3.35
-2.9
-2.8
Irritative:
Baseline mean 10.8 t 1.8
11.1 2 1.5 11.6 -t 1.8
11.4 ? 1.8
11.1 t 2.0
15.9 ? 3.0
16.5 t 2.7 16.7 t 2.6
16.1 t 2.8
16.5 t 2.3
Mean changet
-1.0
-1.0
-1.79
- 1.3
-1.2
-1.1
-1.4
-2.0
-1.7
-2.0
* Values are mean plus or minus standard deviation. Total symptom score is the obstructive symptom score plus the irritative symptom score.
t Mean changes aajusted for baseline effect.
$ Significantly different from placebo mean changes, p <0.01.
5 Significantly different from placebo mean changes, p <0.05.

verity. Overall, the incidence of adverse events did not increase with increasing dose or duration of treatment. A tendency was noted for older patients (65 years old or older) to
experience fewer adverse events than younger patients (43%
versus 54%, respectively).
Adverse events caused 11.1% of the patients receiving doxazosin and 4.1% of those receiving placebo to withdraw from
the study. The most common adverse events leading to discontinuation were dizziness, headache and hypotension.
DISCUSSION

Consistent with the new Agency for Health Care Policy and
Research guidelines, patients with moderate symptoms of
BPH should be offered treatment options. Patients with mild
or moderate symptoms of BPH often prefer nonoperative
management of the disease. Current nonoperative options
include the use of selective al-adrenoceptor antagonists or
finasteride, a 5a-reductase inhibitor. Finasteride inhibits the
conversion of testosterone to dihydrotestosterone, thus decreasing the size of the prostate and improving urine flow in
approximately a third of all treated patients. However, finasteride may require 6 to 12 months of use before a significant decrease in prostatic size occurs. On the other hand, in
our study doxazosin produced a significant and rapid improvement in urinary flow rate (within1 week)early in the
treatment regimen. Terazosin has also been reported to have
an early, significant effect on maximum flow rate.8 Although
the benefit of combination therapy with a 5a-reductase inhibitor plus an al-adrenoceptor antagonist has been pro-

posed, a preliminary study did not show any significant improvement of a 2-drug combination over an al-adrenoceptor
antagonist alone.16
Doxazosin, the selective al-adrenoceptor antagonist used
in this double-blind study of patients with BPH and hypertension, significantly improved both conditions. With respect
to BPH, maximum urinary flow rates increased significantly
with 4 mg., 8 mg. and 12 mg. doxazosin compared to placebo
by 2.3 to 3.6 ml. per second, and average urine flow rates
increased significantly by 1.3 to 2.1 ml. per second, depending on the dose level and time of measurement. Signiscant
improvements in the BPH symptom scores for total,obstructive and irritative symptoms were noted with 4 mg. and 8 mg.
doxazosin compared to placebo. Since 12 mg. doxazosin were
not superior to the 8 mg. dose, 8 mg. appear to be the
maximal effective dose, with significant therapeutic benefit
also occurring with 4 mg. The BPH results from our study
compare favorably to results with other al-adrenoceptor antagonists and with other doxazosin studies.7.8.17-20
Doxazosin has previously been demonstrated to be an effective, well tolerated antihypertensive agent suitable for
once daily administration (plasma half-life 22
and is
well tolerated by elderly patients.2l.m Our study supports
the efficacy of doxazosin in hypertension. with clinically and
statistically significant decreams in patient mean systolic
and diastolic blood pressures occunring with doxazoain compared to placebo.
In general, the al-adrenoceptor antagonista produce few
serious side effects. The selective agents clearly produce

114

DOXAZOSIN FOR BENIGN PROSTATIC HYPERPLASIA AND HYPERTENSION

I 0Sysldic IllDiastolic I

FIG. 3. Mean change from baseline in systolic and diastolic blood pressures (mm. Hg) with patient in sitting position minus mean analysis
a t trough.
TABLE4. Commonly reported adverse events
9
i pts.

Adverse Event

Placebo
(49 pts.)

Doxazosin
(199 pts.)

Overall
Dizziness
Headache
Fatigue

35
4
18
0

48

19
14

10

fewer adverse reactions than the nonselective agents. In our

study the most common side effects were dizziness, headache
and fatigue. The incidence of adverse experiences reported in
our study is similar to that noted previously in other doubleblind BPH trials.*lDoxazosin was well tolerated by all age
groups. In addition, the safety profile was similar to that
noted in earlier hypertension trials, in which the safety of
doxazosin was firmly established.21 Doxazosin, therefore,
would be a suitable agent to treat patients with mild to
moderate BPH and essential hypertension.
CONCLUSIONS

Doxazosin was shown to be significantly superior to placebo in increasing urinary flow and decreasing the total,
obstructive and irritative symptoms of BPH. Compared to
placebo, doxazosin also produced a clinically significant decrease in blood pressure in patients with mild to moderate
hypertension. The drug has the important advantages of
rapid onset of efficacy and once daily dosing, and thus it
should improve compliance in patients who may be on multiple medications. In addition, doxazosin does not adversely
affect lipid profiles or glucose tolerance,P" which is important
since a significant percentage of patients in this age group
have varying degrees of dyslipidemia and/or impaired glucose intolerance or diabetes mellitus. These data strongly
support the use of doxazosin as a nonoperative therapeutic
alternative in the management of BPH. Doxazosin would be

particularly useful in the management of patients who have

BPH plus hypertension.
Drs. J. Y. Gillenwater (consultant), R. L. Conn, S. G.
Chrysant and J. Roy, and the Multicenter Study Group have
participated in clinical studies sponsored by Pfizer Central
Research, New York. Drs. Ahmed Fawzy, Ira Klimberg and
David F. Mobley (consultants), and Michael D. Campbell
(project scientist) also assisted in the preparation of this
article.
REFERENCES

1. Walsh, P. C.: Benign prostatic hyperplasia. In: Campbell's Urol-

ogy, 6th ed. Edited by P. C. Walsh, A. B. Retik, T. A. Stamey

and E. D. Vaughan, Jr. Philadelphia: W. B. Saunders Co., vol.
1, chapt. 25, pp. 1009-1028, 1992.
2. Caine, M., Raz, S. and Ziegler, M.: Adrenergic and cholinergic
receptors in the human prostate, prostatic capsule and bladder
neck. Brit. J. Urol., 47: 193, 1975.
3. Caine, M. and Schuger, L.: The capsule in benign prostatic
hypertrophy. Department of Health and Human Services, National Institutes of Health Publication No. 87-2881, p. 221,
1987.
4. Furuya, S., Kumamoto, Y., Yokoyama, E., Tsukamoto, T., Izum,

T. and Abiko, Y.: Alpha-adrenergic activity and urethral pressure in prostatic zone in benign prostatic hypertrophy. J.
Urol., 128: 836, 1982.
5. Christensen, M. M. and Bruskewitz, R. C.: Clinical manifestations of benign prostatic hyperplasia and indications for therapeutic intervention. Urol. Clin. N. h e r . , 17: 509, 1990.
6. Caine, M., Pfau, A. and Perlberg, S.: The use of alpha-adrenergic
blockers in benign prostatic obstruction. Brit. J. Urol., 48: 255,
1976.
7. Kirby, R. S., Coppinger, S. W., Corcoran, M. O., Chapple. C. R.,

Flannigan, M. and Milroy, E. J.: Prazosin in the treatment of

prostatic obstruction. A placebo-controlled study. Brit. J.
Urol., W.136, 1987.
8. Lepor, H., Auerbach, S.. Puras-Baez. A,, Narayan. P.. Soloway,
M., Lowe, F.. Moon, T.. Leifer. G. and Madsen. P.: A randomized, placebo-controlled multicenter study of the eflicacy and

DOXAZOSIN FOR BENIGN PROSTATIC HYPERPLASIA AND HYPERTENSION

115

safety of terazosin in the treatment of benign prostatic hyper- 16. Lepor, H. and Machi, G.: The relative efficacy of terazosin versus
plasia. J. Urol., 148 1467,1992.
terazosin and flutamide for the treatment of symptomatic
9.Jardin, A., Bensadoun, H., Delauche-Cavallier, M. C. and Attali,
BPH. Prostate, 2 0 89, 1992.
P.: Alfuzosin for treatment of benign prostatic hypertrophy.
17. Caine, M., Perlberg, S. and Meretyk, S.: A placebo-controlled
The BPH-ALF Group. Lancet, 337: 1457,1991.
double blind study of the effect of phenoxybenzamine in benign
10. Chapple, C. R., Burt, R. P., Anderson, P. G., Greengrass, P.,
prostatic obstruction. Brit. J. Urol., 5 0 551, 1978.
Wyllie, M. and Marshall, 1.: a1 Adrenoceptor subtypes in the 18. Abrams, P. H., Shah, P. J., Stone, R. and Choa, R. G.: Bladder
human prostate. Brit. J. Urol., 7 4 585, 1994.
outflow obstruction treated with phenoxybenzamine. Brit. J.
11. Janknegt, R. A. and Chapple, C. R.: Efficacy and safety of the
Urol., 54: 527, 1982.
alpha-1 blocker doxazosin in the treatment of benign prostatic 19. Christensen, M. M., Bendix Holme, J., Rasmussen, P. C.,
hyperplasia. Analysis of 5 studies. Doxazosin Study Group.
Jacobsen, F., Nielsen, J., Nmgaard, J. P., Olesen, S., Noer, I.,
Eur. Urol., 24: 319, 1993.
Wolf, H. and Husted, S. E.: Doxazosin treatment in patients
12. Pool, J. L.: Role of the sympathetic nervous system in hypertenwith prostatic obstruction. A double-blind placebcontrolled
sion and BPH. Brit. J. Clin. Pract., 74: 13, 1994.
study. Scand. J. Urol. Nephrol., 21:39, 1993.
13. Young, R. A. and Brogden, R. N.: Doxazosin. A review of its 20. Chapple, C. R.,Carter, P., Christmas, T. J., Kirby, R. S., Bryan,
pharmacodynamic and pharmacokinetic properties and therJ., Milroy, E. J. G. and Abrams, P.: A three-month doubleapeutic efficacy in mild to moderate hypertension. Drugs, 35:
blind study of doxazosin as treatment for benign prostatic
525, 1988.
outlet obstruction. Brit. J. Urol., 74: 50, 1994.
14. Elliott, H. L., Meredith, P. A. and Reid, J. L.: Pharmacokinetic 21. Hayduk, K.: Efficacy and safety of doxazosin in hypertension
overview of doxazosin. h e r . J. Cardiol., 5 9 78G, 1987.
therapy. Amer. J. Cardiol., 5 9 35G, 1987.
15. Boyarsky, S.,Jones, G., Paulson, D. F. and Prout, G. R., Jr.: A 22. Rosenthal, J.: A multicenter trial of doxazosin in West Germany.
new look a t bladder neck obstruction by the Food and Drug
Amer. J. Cardiol., 5 9 40G, 1987.
Administration regulators: guidelines for investigation of be- 23. Pool, J. L.: Effects of doxazosin on coronary heart disease risk
nign prostatic hypertrophy. Trans. h e r . Ass. Genito-Urin.
factors in hypertension and BPH. Brit. J. Clin. Pract., 74: 8,
Surg., 88: 29, 1977.
1994.