Pharmacology & Pharmacy, 2011, 2, 338-340
doi:10.4236/pp.2011.24043 Published Online October 2011 (
Copyright © 2011 SciRes. PP
Frequent Episodic Vertigo Is an Unexpected Side
Effect of Flutamide
Jiann-Jy Chen1,2, Dem-Lion Chen3*
1Department of Medical Imaging, Taipei Medical University & Shuang Ho Hospital, New Taipei, Chinese Taipei; 2Department of
Otorhinolaryngology, Tao-Yuan Hospital, Department of Health, Executive Yuan, Taoyuan, Chinese Taipei; 3G-Home Otorhi-
nolaryngologic Clinic, Kaohsiung, Chinese Taipei.
Email: *
Received April 28th, 2011; revised May 28th, 2011; accepted July 29th, 2011.
An 82-year-old male suffered from prostatic cancer five years ago. Since then, he has taken flutamide and was bothered
with episodic vertigo (EV) every morning. In order to treat prostatic cancer, flutamide was not discontinued, but con-
servative treatment and life-style change were recommended. Finally, EV actually subsided. Herein, we report the rare
case, in which EV was an unexpected side effect of flutamide. Herein we review his whole history, physical examination,
vestibular function test, electronystagmogram, caloric test, awake encephalogram, blood examinations, color-coded
duplex ultrasonogram and magnetic resonance imaging/angiogram to suggest a mechanism of flutamide responsible for
Keywords: Flutamide, Episodic Vertigo, Prostatic Cancer
1. Introduction
Flutamide (4’-nitro-3’-trifluoromethylisobutyranilide) could
antagonize the nuclear androgen receptors of prostatic
cancer, and inhibits intake of androgen; so, it has been
widely applied to treat prostatic cancer. The main ad-
verse reactions are reported diarrhea, nausea, vomiting,
gastrointestinal distress, gynecomastia, muscular cramps
and cardiovascular complications [1,2], and never epi-
sodic vertigo in the literature, but we encountered a case
of frequent episodic vertigo after taking flutamide. Here-
in we report it because of rare curiosity and suggest a m-
chanism responsible for the side effect.
2. Case Report
A right-handed 82-year-old male has height 166 cm,
weight 55 kg, and body mass index 20.0 kg/m2. He did
not suffer head trauma, hypertension, diabetes mellitus,
heart disease, migraine or psychosis; neither did he have
any hobby of cigarette smoking, alcohol drinking, areca
chewing, or coffee consumption. However, he has regu-
larly taken doxazosin (Doxaben) or terazosin (Hytrin) to
treat benign prostatic hyperplasia for 12 years. Five years
ago, he unfortunately got stage II prostatic adenocarci-
noma and began taking anti-androgen flutamide (Fugerel)
every day. Since then, he has bothered with episodic ver-
tigo every early morning. Changing position exacerbated
symptom, and only bed rest would relieve symptom in
half an hour. There was no headache, blurred vision,
ataxia, syncope, tinnitus, hearing block or other neurolo-
gic signs.
Three years ago, he first visited our emergency due to
sever episodic vertigo with nausea and vomiting. Blood
pressure (heart rate) was 122/78 mmHg (59/min). One
hour after he was treated conservatively, symptoms sub-
sided, and blood pressure (heart rate) was 142/89 mmHg
(86/min). Then, Doxazosin or Terazosin was discontin-
ued, but episodic vertigo still recurred every early morn-
ing. Last July, he visited our emergency again. Blood
pressure (heart rate) was 128/79 mmHg (47/min). When
symptoms subsided, blood pressure (heart rate) rose to
138/89 mmHg (72/min). Computed tomography of brain
was unremarkable. In the following three days, he was
assigned to the author for a battery of studies.
Physical examination and vestibular function test were
normal, except that squat to stand test or hyperventilation
test provoked the same vertigo. Electronystagmogram,
caloric test, awake encephalogram and blood examina-
tions were unremarkable. Color-coded duplex ultrasono-
gram (EnVisor, Philips, USA) revealed mild atheroscle-
rosis over bilateral common carotid arteries, and total
Frequent Episodic Vertigo Is an Unexpected Side Effect of Flutamide339
cerebral flow volume was 760 mL/min, which was the
sum of bilateral internal carotid arterial volumes and bi-
lateral vertebral arterial volumes (Table 1). Twenty-four
hours’ Holter showed that heart rate was averaged 68
beats/min with highest 114 beats/min (8:00 am) and low-
est 42 beats/min (4:00 AM). T1, T2, fluid-attenuated
inversion recovery and diffusion weighted image mag-
netic resonance imaging (1.5 Tesla system, Picker Edge
Eclipse, Picker 98 International, USA) did not find any
lesion, but time of flight magnetic resonance angiogram
(TOF MRA)(TR/TE/excitation: 29/6/1) showed central
vascular anomalies: 1) posterior incomplete circle of
Willis (Figure 1(a)) and 2) tortuous vertebrobasilar ar-
tery (Figure 1(b)).
In order to suppress prostatic cancer, flutamide was
not discontinued, so he was conservatively treated with
diphenidol (Cephadol), ginkgo flavone (Jinbo), and aspi-
rin (Bokey); besides, he was asked to slow down getting
up or changing position in early morning. One week later,
symptom did not recur any more. In the following half a
year, it was uneventful although he did not take dipheni-
dol, ginkgo flavone, and aspirin any more.
3. Discussion
He has been bothered with episodic vertigo every early
morning for five years. Doxazosin or terazosin, long-
acting selective α1-antagonist, is known to treat benign
prostatic hyperplasia and hypertension by relaxing
smooth muscle of vessels, urinary bladder and prostate;
however, it could induce dizziness (vertigo), fatigue,
hypotension, edema and dyspnea via the same mecha-
nism [3,4]. α1-antagonists have been discontinued after
1st-time emergency, but symptom did not relieve any
more; thus, symptom was by far not a side effect of
α1-antagonist. Symptom always subsided after heart rate
and blood pressure have risen in these two emergencies;
besides, squat to stand test and hyperventilation test in-
duced the same symptom; thus, symptom was associated
with cardiovascular dysfunction and central nervous he-
modynamic instability although 24-hour electrocardio-
gram was normal.
Seventy four point six percent of 18 - 89 year-old Tai-
wanese have defects of posterior circle of Willis, and
among them, 57.4% are short of bilateral posterior com-
municating arteries (Figure 1(a)) [5], and communica-
tion of anterior and posterior circulation must be limited
[6]. It is probable that vertebrobasilar arterial system de-
generated abnormally in the 5th embryologic week, and
resulted in bilateral intracranial vertebral artery tortuosity.
After birth, asymmetric blood flows of vertebral artery
gradually bended basilar artery year by year (Figure 1(b))
[7]. Finally, tortuous vertebrobasilar artery might become
locally more thrombogenic secondary to vascular resis-
Table 1. Color-coded duplex ultrasonogram of extracranial
vertebral arteries.
Average velocity
Average flow
Right3.09 14.9 67 0.69
Left3.68 16.3 104 0.65
(a) (b)
Figure 1. (a) TOF MRA showed dislinkage of anterior and
posterior circulation (dotted lines) due to absence of bilat-
eral posterior communicating arteries; (b) the axis of ver-
tebrobasilar artery (black line) rotated clockwise (dou-
ble-headed curved arrow). The upper extreme and middle
of basilar artery (diameter 4.0 mm) were respectively 2.9
mm (hollow arrow head) and 5.1 mm (hollow arrow) apart
from mid-line (white spotted line). Before connecting basi-
lar artery, right vertebral artery (diameter 2.0 mm) formed
a sigmoid route, and so did left vertebral artery (diameter
3.8 mm) a crooked route. The rightward extreme of left
vertebral artery was 4.5 mm (filled arrow) apart from mid-
line (white spotted line), and approximated to right verte-
bral artery (filled arrow head).
tance. Therefore, these central vascular anomalies might
incur vertebrobasilar artery insufficiency at specific con-
dition although neck duplex scanning was unremarkable
(Table 1).
Androgen is known to not only keep artery or arteriole
sensitive to baroreflex [8], but also provoke the pathway
of nitrogen-monoxide genesis in central nervous system,
activating angiotensin II system and raising blood pres-
sure [9]. After he has had to regularly take Flutamide to
suppress prostatic cancer, Flutamide has antagonized
androgen receptors of central nervous system, heart, and
peripheral arterioles; so, regulation of blood pressure and
heart rate were limited.
Sudden getting up or changing position could incur
transient vertebrobasilar artery insufficiency secondary to
postural hypotension, especially during low sympathetic
tone in early morning. We suggest that not only age, but
also Flutamide has limited the immediate compensation
Copyright © 2011 SciRes. PP
Frequent Episodic Vertigo Is an Unexpected Side Effect of Flutamide
Copyright © 2011 SciRes. PP
of heart rate and blood pressure for transient vertebro-
basilar artery insufficiency; fortunately, simply episodic
vertigo resulted, but not ischemia stroke. However, it was
beyond neck duplex scanning to identify transient verte-
brobasilar insufficiency; besides, it was beyond electro-
nystagmogram and caloric test to identify transient ves-
In order to suppress prostatic cancer, Flutamide was
not discontinued, and conservative treatment and life-style
change were recommended as below. Diphenidol has
been tried to relieve vertigo. Ginkgo flavone and aspirin
have also been tried to decrease the vascular resistance of
vertebrobasilar artery. In order to spare his heart enough
time to compensate for postural hypotension, he was
asked to slow down getting up or changing position. As a
result, episodic vertigo did not recur in one week despite
daily flutamide. In the following over half a year, it was
uneventful although he has not taken diphenidol, ginkgo
flavone and aspirin any more. Herein, we report the case,
in which EV was an unexpected side effect of flutamide.
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