Bladder storage problems include overactive bladder (OAB), benign prostatic hyperplasia (BPH), detrusor overactivity, bladder inflammation, and bladder pain syndrome.

Storage problem, whether functional or anatomic, is related with reduced bladder capacity especially at night. Nocturia occurs when the amount of urine production overwhelm the nocturnal bladder capacity during the night. Therefore, even without exceeding production of urine at night, the bladder cannot store the nocturnal urine volume.

The reasons for the urinary bladder to have this condition are multiple ways: significant following-voiding residual urine due to reduced bladder contractility often seen with associated bladder outlet obstruction caused by benign prostatic obstruction (BPO). OAB or detrusor overactivity may have patients wake up via urgency feeling or bladder filling sense caused by uninhibited contraction. Specific pain of bladder Inflammation or bladder pain syndrome also induce sensory urgency and reduced functional bladder capacity. Lower urinary tract calculi or primary bladder pathology also could cause a reduction in the anatomic capacity.

Increased urine output can be divided into 24-hour polyuria and NP. In particular, NP is an important contributor to nocturia. NP is typically defined as a nocturnal urinary output >20% of the daily total in young adults and >33% in older adults [1]. The currently recognized contributors to NP include increased fluid intake or diuretic intake during the evening (behavioral etiology), return of water of daytime third spacing in the lower extremities, obstructive sleep apnea (OSA), and lack of production of endogenous pituitary arginine vasopressin.

Nocturia may be associated with sleep apnea. Community-based elderly populations who have higher levels of sleep disordered breathing (>25 breathing events/h) have nearly double the number of nocturia episodes compared with those with low rates of OSA [12]. Nocturia episodes in these individuals can be at least partially reduced by continuous positive airway pressure treatment for sleep apnea [13]. By contrast, one population-based study reported that there is no relationship between nocturia frequency and OSA parameters [14]. OSA does not only awaken the patient but also causes NP. OSA results in hypoxia and hypoxia-induced pulmonary vasoconstriction, which in turn leads to elevated atrial natriuretic polypeptide, which increases urine production at night [15].

Lifestyle modification is often given as a first-line option, but there are limitations to controlling nocturia by lifestyle modification only. The information regarding this topic is very scarce compared to its significance and more research should be needed in this topic in the future.

Some modifications include preemptive voiding, nocturnal dehydration, dietary and fluid restrictions (avoidance of caffeinated beverages, alcohol, etc.), medication timing (diuretics in the midafternoon), evening leg elevation to mobilize fluids, use of sleep medications or sleep aides, and use of protective undergarments [2]. Although no randomized controlled trials (RCTs) evaluating the effect of behavioral modification on nocturia as a primary outcome have been found, one study showed that the education about life style modification could reduce nocturia episode and related quality of life [17].

Several drugs used in LUTS/BPH medication have shown effects on nocturia and, alpha blocker was thought to reduce residual urine and so increase room for nocturnal urine storage. However, it is doubtful whether alpha-blockers have clinical significance, because the difference in nocturia episodes was too small between treatment with alpha-blockers and placebo. The effect of tamsulosin was assessed in a phase 3B pilot study involving men with LUTS/BPH and at least 2 voids per night [18]. The study concluded that "tamsulosin 0.4 mg was superior to placebo in reducing nocturia." However, this "significant reduction" amounted to a mean change of 3.1 to 2.3 awakenings for placebo and 3.1 to 2.0 for the drug. One RCT compared an α1-blocker with placebo, with a focus on nocturia as a primary outcome. The primary endpoint was the mean variation in the number of nocturnal voids compared with baseline after 8 weeks of treatment with a tamsulosin oral controlled absorption system (OCAS) 0.4 mg/d or placebo. The mean decrease in the number of nocturnal voids was not significantly different between the two groups (0.7 for placebo compared with 1.1 for tamsulosin OCAS) [19]. Another study was a secondary analysis of IPSS nocturia data from the Veterans' Administration Cooperative Study [20]. The data from 1,078 men aged 45-80 years with a diagnosis of BPH and who completed 12 months of the trial were analyzed specifically for reductions in nocturia. There were four arms in the study: terazosin, finasteride, combined terazosin plus finasteride, and placebo. The study presented significant results for α1-blockers and combination over placebo but with a very slight effect. Recently, a few studies have reported the effect of a selective alpha-1D blocker, naftopidil, on nocturia. One study compared the efficacy of two α1-adrenoceptor antagonists, tamsulosin and naftopidil, in the treatment of LUTS with BPH [21]. They concluded that the two drugs had similar efficacy in the treatment of BPH symptoms. However, naftopidil was better than tamsulosin for nocturia. The improvement in the tamsulosin group was from 3.4 to 3.1 voids per night; the improvement in the naftopidil group was from 3.4 to 2.3 voids per night. However, the sample number was small and the study period was too short. We must wait for further long-term, well-designed controlled studies on naftopidil to be convinced of its positive effect on nocturia. In conclusion, most studies on α1-blockers have been conducted in the context of LUTS/BPO management, and the evidence supporting the efficacy of α1-blockers in treating nocturia is low.

The majority of studies on antimuscarinics have been conducted in the context of OAB management. Because nocturia is commonly seen in OAB, it has been assumed that first-line medications for OAB will exert a clinically significant effect and will show a somewhat positive effect on reducing the number of nocturia episodes for patients without OAB symptoms. However, there is limited evidence showing that antimuscarinics are efficient for the management of nocturia.

Diuretics are often prescribed for peripheral edema with no particular attention to the time of the day at which they would be most effective. In patients with NP owing to reabsorption of third-space lower extremity fluid in the supine position during sleep, diuretics should be administered in the midafternoon to address fluid accumulated over the course of the day, but not so late as to actually exacerbate NP. One trial compared furosemide intake 6 hours before bedtime with placebo. Furosemide 6 hours before bedtime was superior to placebo in reducing the number of nocturnal voids [26]. One preliminary study showed terazosin and thiazide combination therapy could reduce nocturia more than 25% in about half of the study patients [27].

For patients whose nocturia is related to NP, either alone or combined with OAB or BPH, antidiuretic treatment that reduces nocturnal urine volume is effective. Before antidiuretic treatment, patients should be given advice regarding nighttime fluid intake along with other causes of NP; clinicians should exclude possible causes of NP in these patients. As previously described, NP may occur secondary to any renal tubular dysfunction, third-space fluid sequestration, OSA, circadian impairment, or as a side-effect of drugs (e.g., steroids). For those patients with suspected fluid sequestration (which is a possibility in patients with venous insufficiency, hypoalbuminemia, congestive cardiac failure, etc.), one can consider compression and elevation or the use of a diuretic in the afternoon. Desmopressin is the synthetic analogue of arginine vasopressin. Desmopressin has a more powerful and longer-lasting antidiuretic action than does arginine vasopressin. It increases reabsorption of water in the distal and collecting tubules of the kidney via its action on the V2 receptor and then concentrates the urine, decreasing urine production and postponing the need to void. Given the specific antidiuretic action of desmopressin, it is the pharmacological therapy of choice for patients with nocturia in which NP is present and has a grade A level 1 recommendation from the International Consultation on Incontinence [28].

Sleep disturbance can result from sleep disorders; medical, neurological, or psychiatric diseases; and other influences, which are evaluated when treating nocturia. Patients suspected of having a sleep disorder (e.g., sleep apnea, nocturnal seizures, and excessive daytime sleepiness) should be referred to a sleep specialist. Short-acting hypnotics may be helpful for patients with sleep disturbances. Oxazepam has been associated with a reduction in nocturia (but not nocturnal urine production) [34].

Although surgical or interventional therapy is not indicated for nocturia, transurethral resection of the prostate (TURP) appears to confer a greater improvement in BPH symptoms including nocturia, and several studies reported a decrease in the mean number of nocturia episodes after TURP [35,36]. The mechanism of improvement in symptoms after TURP is not clear. Possible explanations include a reduction in detrusor overactivity with relief of prostatic obstruction and the effect of adenoma removal on the detrusor muscle.