EURURO Vol. 72 No. 5

758 860

1. Introduction
Nocturia is defined by the International Continence Society
(ICS) as the complaint that an individual has to wake at night
one or more times to void It reflects the relationship
between the amount of urine produced while asleep, and the
storage by the bladder of urine received. Nocturia can occur
as part of lower urinary tract dysfunction (LUTD), notably in
overactive bladder syndrome (OAB). Nocturia can also occur
in association with other forms of LUTD, such as bladder
outlet obstruction or chronic pelvic pain syndrome. Nocturia
is a feature of systemic conditions affecting water and salt
balance leading to excessive production of urine at all
times (global polyuria) or primarily at night (nocturnal
polyuria), so that nocturia can be a systemic symptom
For example, cardiovascular, endocrine, and renal
disease can affect water and salt homeostasis , leading to
increased rate of urine production.
Summarizing the causative categories for nocturia, the
International Consultation on Male Lower Urinary Tract
symptoms (LUTS) listed:
1. Bladder storage problems;
2. 24-h (global) polyuria (> 40 ml/kg urine output over a
24-h period);
3. Nocturnal polyuria (nocturnal output exceeding 20% of
24-h urine output in younger patients, or 33% of urine
output in people aged over 65 yr );
4. Sleep disorders;
5. Mixed etiology.
Thus, the treatment of nocturia is potentially complex,
and was identified by the European Association of Urology
Guidelines Panel for Male [7_TD$DIFF]non-neurogenic LUTS as a key
challenge. The aim of the current systematic review of
treatment was to assess and compare available therapy
options for nocturia, in terms of symptom severity and
quality of life. The review focusses on men, in view of the
differing lower urinary tract anatomy and medication
options available compared with women.
2. Evidence acquisition
The objectives were to determine the relative benefits and
harms of treatment options for nocturia, and to perform
subgroup and/or sensitivity analysis.
The Embase, Medline, Cochrane Systematic Reviews, and
Cochrane Central (Cochrane Health Technology Assessment,
Database of Abstracts of Reviews of Effects, Health
Economics Evaluations Database) were searched with no
restriction on date of publication (date of final search
September 2016). The search strategy was registered on
PROSPERO on October 21, 2015
. Comparative studies were included
(randomized controlled trials [RCTs], and nonrandomized
comparative studies [both prospective and retrospective,
interventional, or observational]), studying adult men
(male-only or mixed sex populations), with nocturia or
nocturnal polyuria as a primary outcome, categorized within
the following symptom groups:
1. Nocturia (ICS definition , or as defined by trialist) as
the primary presentation (ie, nocturia as the predomi-
nant bothersome symptom);
2. Nocturia as a secondary component of LUTS (ie, LUTS
including nocturia);
3. Nocturnal polyuria (ICS definition , or alternative
definition if stated by the investigating group).
Interventions included: anticholinergics, mirabegron,
a-blockers, 5-a reductase inhibitors, oral phosphodiester-
ase-5 inhibitors, desmopressin, diuretics, sleep-promoting
agents, and phytotherapy. Comparator controls were:
no treatment, placebo, and alternative experimental
treatment.
The primary outcomes were:
- Symptom severity for nocturia (outcome measure defined
as < 2 episodes, or cure [ie, no episodes of nocturia] or
reduction in nocturia episodes, or as defined by trialist);
- Quality of life for nocturia.
The secondary outcomes were:
- Harms: adverse events of treatment and events leading to
potential harm (eg, hyponatremia, voiding difficulties),
withdrawal, or drop-out rates;
- Any other outcomes judged relevant by reviewer.
Two review authors independently screened the titles
and abstracts of identified records, and the full text of
potentially eligible records was evaluated using a stan-
dardized form. Risk of bias was assessed, including: random
sequence generation, allocation concealment, blinding,
incomplete outcome data, selective reporting, and other
sources of bias. A list of potential confounders was
Conclusions: Issues of trial design make therapy of nocturia a challenging topic. The range of
contributory factors relevant in nocturia makes it desirable to identify predictors of response
to guide therapy. Consistent responses were reported for titrated antidiuretic therapy. For
other therapies, responses were less certain, and potentially of limited clinical benefit.
Patient summary: This review provides an overview of the current drug treatments of
nocturia, which is the need to wake at night to pass urine. The symptom can be caused by
several different medical conditions, and measuring its severity and impact varies in
separate research studies. No single treatment deals with the symptom in all contexts,
and careful assessment is essential to make suitable treatment selection.
# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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