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Mark Speakman *
Taunton and Somerset Hospital, Musgrove Park, Taunton TA1 5DA, United Kingdom
and that (new) therapies for LUTS/BPH should be patterns and mood. In another study, QoS was
evaluated for their effects on nocturia, quality of evaluated using polysomnography (PSG) and sleep
sleep (QoS), and QoL. diaries in which symptoms such as sleep latency
Several studies have shown that lack of sleep and frequency of awakenings were rated. Although
can seriously affect a person’s physical and mental PSG data could not objectively show improved QoS
well-being and impair performance during the next in this study, the patients reported a subjective
day [4]. In addition, daytime sleepiness is likely to improvement in QoS.
reduce alertness and hence increase the risk of falls Similarly, treatment of OSA, a condition in which
and car accidents [5,6]. In the long run, chronic sleep sleep is disturbed because respiration is decreased
disorders such as nocturia may even increase the or stopped repeatedly, significantly reduces daytime
risk of severe metabolic disorders, such as type 2 sleepiness and improves QoS and QoL of both the
diabetes or cardiovascular disease [7,8]. Because bed patients and their bed partners [15,16]. For QoS and
partners can have a significant impact on each QoL assessment in one of these studies, patients and
other’s sleep, not only the patient with nocturia their bed partners had to complete the Epworth
but also his partner may suffer from disturbed Sleepiness Scale (ESS) questionnaire, the short
sleep and daytime fatigue [9]. Given the potential form health survey (SF-36) and the Calgary Sleep
consequences of nocturia, questions about sleep Apnoea Quality of Life Index (SAQLI). Both the
quality and quantity should be an integral part of patients and their bed partners reported statistically
every history and physical examination of patients significant improvements in total ESS ( p < 0.001 and
with LUTS/BPH. p = 0.02, respectively) and SAQLI scores ( p < 0.001
and p = 0.002, respectively) and in the domains of
role-physical, vitality, social functioning, and men-
2. Managing sleep disorders: impact on tal health of the SF-36 questionnaire. In another
daily life study, improvements in QoS were recorded using
somnographic examinations and sleep quality
Although the association between sleep disorders questionnaires including questions on treatment
on the one hand and daytime sleepiness and QoL on effectiveness, daytime tiredness, and improve-
the other hand is obvious, few clinical data are ments in QoS. Overall, the data of these studies
available showing that successful treatment of sleep show that improving QoS can have a major impact
disorders has an impact on vitality and health. In on a patient’s and even his partner’s performance
the field of LUTS/BPH, several studies showed an and QoL.
improvement of nocturia after surgical or medical
treatment for LUTS/BPH [10–12]. However, these
studies had rather low power and were not 3. Managing nocturia in patients with
specifically designed to measure the improvement LUTS/BPH
of nocturia. Moreover, none of these studies assessed
the impact of nocturia on QoS or QoL. Sleep disorders 3.1. Initial patient evaluation
other than nocturia that are common in the elderly
include restless leg syndrome and obstructive sleep Lifestyle changes such as reduced fluid intake or
apnoea (OSA). restriction of alcohol or caffeine may help some
Use of medical therapy to reduce the frequency patients with nocturia, but successful management
of periodic leg movements in patients with restless of nocturia usually implies treatment of its under-
leg syndrome has been shown to significantly lying cause. Therefore, patients with nocturia
increase total sleep time. Various studies in this should be adequately evaluated to assess the cause
field showed that this results in significant improve- of their complaint. Initial patient screening includes
ments in QoS and QoL [13,14]. Leg movements in a detailed history and physical examination [17].
these studies were recorded by actigraphy; QoL was The patients are questioned about timing and
evaluated using modified 50-mm Hamburger Visual amount of fluid intake, use of medications, and
Analogue Scales covering domains on life satisfac- health problems and undergo physical and neuro-
tion (eg, satisfaction with cognitive performance, logic examinations. In addition, the patients have to
activities of daily living, leisure activities, and complete a 24-h diary including information on
efficacy at work) and burden caused by symptoms timing and frequency of voiding and urine volume to
(eg, depression, fatigue, and physical symptoms). In distinguish between the different categories of
one of the studies, the standardised sleep inventory nocturia, that is, polyuria, nocturnal polyuria, and
short form-A (SF-A) was used to assess sleep reduced bladder capacity [17–19].
596 european urology supplements 6 (2007) 594–599
3.2. Treatment of nocturia due to BPH available a1-AR antagonists are similarly effective in
relieving LUTS/BPH, but tamsulosin differs from the
Patients with nocturia associated with BPH may other agents because of its greater selectivity for the
benefit from drugs affecting either prostate volume a1A- and a1D-ARs [21]. Therefore, it is less likely
or muscle tone in the lower urinary tract (LUT) or to cause vasodilatation-associated adverse events
from prostate surgery. Currently, a1-adrenoceptor (AEs) such as dizziness and orthostatic hypotension.
(a1-AR) antagonists such as alfuzosin, doxazosin, Tamsulosin has been available in a modified-release
and tamsulosin are recommended as first-line (MR) capsule formulation for many years and
pharmacologic therapy for men with LUTS/BPH several clinical studies have assessed its efficacy
[20]. The a1-AR antagonists improve urinary flow and safety versus placebo [22–24]. Drug delivery
and other symptoms of BPH by reducing muscle systems for a1-AR antagonists such as the MR
tone in the bladder neck, the urethra, and the capsule were developed to provide a gradual and
prostate. Three distinct types of a1-ARs, the a1A-, continuous drug release but are usually dependent
a1B-, and the a1D-ARs, exist. Contraction of the on the presence of water for drug release [25–27].
muscles of the human LUT is mainly mediated by Unfortunately, whereas the stomach and the small
a1A-ARs and a1D-ARs, whereas a1B-ARs are predo- intestine contain enough water to allow drug release
minantly present in the vasculature. All currently in the upper gastrointestinal (GI) tract, water is only
Fig. 1 – (A) The pharmacokinetic (PK) profile of tamsulosin oral controlled absorption system (OCAS) 0.4 mg shows a reduced
Cmax and a consistent and continued 24-h plasma concentration of tamsulosin (mean PK profile of eight subjects).
(B) Scintigraphic analysis shows that tamsulosin is released from the OCAS tablet throughout the entire gastrointestinal
tract, including the colon. Reprinted from Stevens et al [30], with permission from Librapharm Limited.
european urology supplements 6 (2007) 594–599 597
scarcely available in the colon. This means that drug tablet core was observed, this occurred within the
release from these formulations only persists until colon (Fig. 1). Release time or site from the tablet
arrival in the colon, that is, <24 h. Moreover, release core was not affected by individual variations in
from these formulations usually also depends on gastric residence, small intestinal transit, or colonic
food intake. Administration of the tamsulosin MR residence. Altogether, the PK and scintigraphic obser-
capsule on an empty stomach increases the max- vations strongly suggest that tamsulosin is slowly
imum plasma concentration (Cmax) and the area released from the OCAS tablet throughout the entire
under the curve, which might increase the risk of GI tract, including the colon, leading to a continuous
peak-level associated AEs [28]. Therefore, tamsulo- and consistent 24-h plasma concentration.
sin MR has to be taken after the first meal of the day.
4.2. Effect of tamsulosin OCAS on nocturia, QoS, and QoL
addition, the investigators found a significant [10] Yoshimura K, Ohara H, Ichioka K, et al. Nocturia and
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Kitamura T. Significance of nocturia in the International
the HUS and the improvement in QoL on the other
Prostate Symptom Score for benign prostatic hyperplasia.
(Spearman coefficient 0.63 and 0.64, respectively).
J Urol 2002;167:172–6.
These findings suggest that improving nocturia
[12] Johnson TM, Jones K, Williford WO, Kutner MH, Issa MM,
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well-being. benign prostatic hyperplasia: secondary analysis of the
Department of Veterans Affairs Cooperative Study Trial.
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5. Conclusions [13] Trenkwalder C, Stiasny K, Pollmacher T, et al. L-dopa
therapy of uremic and idiopathic restless legs syndrome:
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QoL. Unfortunately, currently available treatments
[15] Fransson AM, Tegelberg A, Leissner L, Wenneberg B,
are not specifically designed to treat nighttime
Isacsson G. Effects of a mandibular protruding device
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