World J Urol (2014) 32:1163–1170 DOI 10.1007/s00345-014-1381-7
TOPIC PAPER
Impact of desmopressin on nocturia due to nocturnal polyuria in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) Richard Berges · Klaus Höfner · Michael Gedamke · Matthias Oelke
Received: 6 August 2014 / Accepted: 8 August 2014 / Published online: 19 August 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose To evaluate the efficacy of desmopressin on nocturia, quality of sleep (QoS), and health-related quality of life (HRQoL) in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and nocturia due to nocturnal polyuria (NP) as the predominant symptom. Methods A German observational, multicenter, post-marketing surveillance study including men with LUTS/BPH and nocturia due to NP starting 3 months of desmopressin treatment. Results In total, 137 patients with a mean of 3.8 nocturnal voids (range 2–7) were included. Desmopressin significantly reduced the mean number of nocturnal voids by 53 %, mean IPSS nocturia question by 50 %, and the mean ratio of night/24-h urine volume by 39 % from baseline to endpoint. The hours of undisturbed sleep significantly increased by 74 %; 71 % of men reported about undisturbed sleep of ≥4 h at study end. Additionally, there was a significant reduction in the Leeds Sleep Evaluation Questionnaire score, indicating a clinically relevant QoS improvement. This was associated with an improved HRQoL, as shown by a significant improvement in both R. Berges PAN-Klinik am Neumarkt, Cologne, Germany K. Höfner Evangelisches Krankenhaus, Oberhausen, Germany M. Gedamke Ferring Arzneimittel GmbH, Kiel, Germany M. Oelke (*) Department of Urology, OE 6240, Hannover Medical School, 30625 Hannover, Germany e-mail: oelke.matthias@mh‑hannover.de
the mean IPSS-QoL question by 43 % and mean ICIQ-N nocturia problem question by 53 %. Concomitant alphablocker use had no effect on the efficacy of desmopressin. The incidence of adverse events was low (2.2 %). Hyponatremia was not observed in any patient. The majority of patients and physicians rated the efficacy and tolerability of desmopressin as good/very good. Conclusions Desmopressin is an effective and well-tolerated treatment for nocturia due to NP in patients with LUTS/BPH in daily practice under routine conditions. Keywords Desmopressin · Lower urinary tract symptoms · Benign prostatic hyperplasia · Nocturia · Nocturnal polyuria · Observational study · Quality of life
Introduction Nocturia is defined as the complaint that the individual has to wake at night one or more times to void [1]. Most people with 20 % in younger and >33 % in older adults [3, 5]. NP is frequently the major underlying
13
1164
cause in many patients with nocturia [6]. A study showed that 83 % of men with nocturia had NP; 20 % had NP alone and about 60 % in combination with factors such as LUTS/BPH [7]. Nocturia can be very bothersome and has a profound negative impact on HRQoL [4]; it is the leading cause of sleep disturbance and sleep fragmentation [8] as well as health care seeking behavior [4]. Sleep disturbance can lead to excessive daytime fatigue and may severely impact daily activities, psychomotor performance, cognitive function, and mood [9, 10]. Reduction of the first sleep period, which consists of deep restorative slow wave sleep (SWS), has a negative effect on daytime activity [8, 11]. Nocturia/impaired sleep can have serious health consequences such as depression, immune suppression, and increased vulnerability for cardiovascular diseases and can cause accidents, falls, and fractures [9, 12–14]. Nocturia is a highly prevalent symptom and one of the most bothersome components in men with LUTS/BPH [4, 15]. These men are typically treated with drugs registered for LUTS/BPH [16, 17]. Effects of these drug classes have been published in other articles of this topic issue (e.g., α-blockers [18], 5ARI [19, 20], PDE5-I [21], and plant extracts [22]), but the impact of these drugs on nocturia is limited. Desmopressin has level 1 evidence and grade A recommendation for the treatment of nocturia due to NP [17, 23, 24]. Randomized, placebo-controlled studies in adults with nocturia due to NP showed that desmopressin can significantly reduce the number of nocturnal voids, decreases the ratio of night/24-h urine volume, and increases the first period of sleep versus placebo [17, 25, 26]. Efficacy is maintained during 10–12 months [27]. In Germany, desmopressin has been licensed for the treatment of nocturia due to NP since 2008. The aim of this observational study was to evaluate under real-life conditions the efficacy and safety of desmopressin in the treatment of nocturia, including its effects on quality of sleep (QoS) and HRQoL, in male patients with LUTS/BPH and nocturia due to NP as the predominant symptom.
Patients and methods Inclusion and exclusion criteria German men with LUTS/BPH and ≥2 nocturia episodes/ night due to NP started desmopressin treatment in a 3-month, non-interventional, multicenter study between 1/2009 and 3/2010. The diagnosis of LUTS/BPH was made by the physician based on patient history, International Prostate Symptom Score (IPSS), 72-h bladder diary, and clinical findings, e.g., physical with digito-rectal examination, (transrectal) ultrasound of the prostate, uroflowmetry,
13
World J Urol (2014) 32:1163–1170
and PVR. Patients were excluded from the observational study if they had polydipsia (urine production >40 mg/kg body weight/24 h), diabetes insipidus, alcoholism, congestive heart failure, treatment with diuretics, hyponatremia, or impaired renal function (creatinine clearance
TOPIC PAPER
Impact of desmopressin on nocturia due to nocturnal polyuria in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) Richard Berges · Klaus Höfner · Michael Gedamke · Matthias Oelke
Received: 6 August 2014 / Accepted: 8 August 2014 / Published online: 19 August 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose To evaluate the efficacy of desmopressin on nocturia, quality of sleep (QoS), and health-related quality of life (HRQoL) in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and nocturia due to nocturnal polyuria (NP) as the predominant symptom. Methods A German observational, multicenter, post-marketing surveillance study including men with LUTS/BPH and nocturia due to NP starting 3 months of desmopressin treatment. Results In total, 137 patients with a mean of 3.8 nocturnal voids (range 2–7) were included. Desmopressin significantly reduced the mean number of nocturnal voids by 53 %, mean IPSS nocturia question by 50 %, and the mean ratio of night/24-h urine volume by 39 % from baseline to endpoint. The hours of undisturbed sleep significantly increased by 74 %; 71 % of men reported about undisturbed sleep of ≥4 h at study end. Additionally, there was a significant reduction in the Leeds Sleep Evaluation Questionnaire score, indicating a clinically relevant QoS improvement. This was associated with an improved HRQoL, as shown by a significant improvement in both R. Berges PAN-Klinik am Neumarkt, Cologne, Germany K. Höfner Evangelisches Krankenhaus, Oberhausen, Germany M. Gedamke Ferring Arzneimittel GmbH, Kiel, Germany M. Oelke (*) Department of Urology, OE 6240, Hannover Medical School, 30625 Hannover, Germany e-mail: oelke.matthias@mh‑hannover.de
the mean IPSS-QoL question by 43 % and mean ICIQ-N nocturia problem question by 53 %. Concomitant alphablocker use had no effect on the efficacy of desmopressin. The incidence of adverse events was low (2.2 %). Hyponatremia was not observed in any patient. The majority of patients and physicians rated the efficacy and tolerability of desmopressin as good/very good. Conclusions Desmopressin is an effective and well-tolerated treatment for nocturia due to NP in patients with LUTS/BPH in daily practice under routine conditions. Keywords Desmopressin · Lower urinary tract symptoms · Benign prostatic hyperplasia · Nocturia · Nocturnal polyuria · Observational study · Quality of life
Introduction Nocturia is defined as the complaint that the individual has to wake at night one or more times to void [1]. Most people with 20 % in younger and >33 % in older adults [3, 5]. NP is frequently the major underlying
13
1164
cause in many patients with nocturia [6]. A study showed that 83 % of men with nocturia had NP; 20 % had NP alone and about 60 % in combination with factors such as LUTS/BPH [7]. Nocturia can be very bothersome and has a profound negative impact on HRQoL [4]; it is the leading cause of sleep disturbance and sleep fragmentation [8] as well as health care seeking behavior [4]. Sleep disturbance can lead to excessive daytime fatigue and may severely impact daily activities, psychomotor performance, cognitive function, and mood [9, 10]. Reduction of the first sleep period, which consists of deep restorative slow wave sleep (SWS), has a negative effect on daytime activity [8, 11]. Nocturia/impaired sleep can have serious health consequences such as depression, immune suppression, and increased vulnerability for cardiovascular diseases and can cause accidents, falls, and fractures [9, 12–14]. Nocturia is a highly prevalent symptom and one of the most bothersome components in men with LUTS/BPH [4, 15]. These men are typically treated with drugs registered for LUTS/BPH [16, 17]. Effects of these drug classes have been published in other articles of this topic issue (e.g., α-blockers [18], 5ARI [19, 20], PDE5-I [21], and plant extracts [22]), but the impact of these drugs on nocturia is limited. Desmopressin has level 1 evidence and grade A recommendation for the treatment of nocturia due to NP [17, 23, 24]. Randomized, placebo-controlled studies in adults with nocturia due to NP showed that desmopressin can significantly reduce the number of nocturnal voids, decreases the ratio of night/24-h urine volume, and increases the first period of sleep versus placebo [17, 25, 26]. Efficacy is maintained during 10–12 months [27]. In Germany, desmopressin has been licensed for the treatment of nocturia due to NP since 2008. The aim of this observational study was to evaluate under real-life conditions the efficacy and safety of desmopressin in the treatment of nocturia, including its effects on quality of sleep (QoS) and HRQoL, in male patients with LUTS/BPH and nocturia due to NP as the predominant symptom.
Patients and methods Inclusion and exclusion criteria German men with LUTS/BPH and ≥2 nocturia episodes/ night due to NP started desmopressin treatment in a 3-month, non-interventional, multicenter study between 1/2009 and 3/2010. The diagnosis of LUTS/BPH was made by the physician based on patient history, International Prostate Symptom Score (IPSS), 72-h bladder diary, and clinical findings, e.g., physical with digito-rectal examination, (transrectal) ultrasound of the prostate, uroflowmetry,
13
World J Urol (2014) 32:1163–1170
and PVR. Patients were excluded from the observational study if they had polydipsia (urine production >40 mg/kg body weight/24 h), diabetes insipidus, alcoholism, congestive heart failure, treatment with diuretics, hyponatremia, or impaired renal function (creatinine clearance
