Nocturia, as defined by the International Continence Society (ICS) 2018: "Nocturia is a highly common and bothersome medical condition characterised by the need to wake up to pass urine during the main sleep period, with each urination followed by sleep or the intention to sleep".¹

The medical literature has not given much attention to the disease, despite the fact that many people wake up in the middle of the night to go to the toilet. However, excessive urination may be related to either the amount of urine available in the bladder after urination or the number of trips to the toilet, as the usual frequency and volume of nocturnal urination across all age groups have not been adequately defined.^2,3 Older people are more prone to nocturia than younger adults, with those over 65 having a higher likelihood of urinating at night. Individuals with nocturia, particularly senior males, may also experience lower urinary tract issues such as frequency, urgency, weak stream and unintentional passing of urine, which are commonly linked to benign prostatic blockage. Women's nocturia is commonly associated with age, childbirth, and menopause.^4,5

Both men and women may experience nocturia for a variety of reasons, such as abnormal behaviour patterns, diuretic medications, coffee, alcohol, or large fluid intake before bed, as well as pathological conditions like diabetes mellitus, prostatic disease, or diabetes insipidus, obstruction of the lower urinary tract, anxiety, or sleep disorders.⁶ Nocturia is prevalent across all populations, nationalities, sexes, and age groups, though rates vary based on assessment parameters. In younger adults (20-40 years), prevalence in men ranges from 11%-35 %.

Nocturia is prevalent across all populations, nationalities, sexes, and age groups, though rates vary based on assessment parameters. In younger adults (20-40 years), prevalence in men ranges from 11%-35.2% for ≥1 voids; in women, it ranges from 20.4%-43.9% for ≥1 voids. In older adults (≥70 years), prevalence in men is 68.9%-93% for ≥1 voids; in women, it is 74.1%-77.1% for ≥1 voids. Nocturia increases with age, but younger adults are also significantly affected, with 15%-20% experiencing ≥2 nightly voids.⁷

In clinical practice, up to 1 in 5 or 6 younger adults consistently wake to void at least twice per night. A population-based study in Finland found that about 40% of both men and women reported 1-2 voids per night. Age-specific analyses reveal that nocturia is more common in young women than young men, but the prevalence in men matches and exceeds that of women in middle age and beyond 60 years.⁸

Pathophysiology of nocturia

The primary factors contributing to nocturia:

Nocturia Polyuria

The term "nocturnal polyuria" refers to the condition in which the volume of urine excreted during sleep is at least 6.4 millilitres per kilogram or more, or at least 20% of the elderly's total daily urine volume.⁹

Mechanisms 

• Excessive fluid intake: Lower urine osmolality is caused by an increase in extracellular fluid volume. Nocturnal polyuria is worsened by illnesses such as congestive heart disease and ageing, which decrease normal renal excretion rates and increase fluid retention, respectively
• AVP changes correlated with age: Generally, elevated plasma osmolality promotes AVP secretion, which lowers urine production. This reaction could not be sufficient in the elderly, which could result in nocturnal polyuria¹⁰
• Medication influence: Diuretics can result in nocturnal polyuria, particularly if used in the evening. AVP secretion can be inhibited and glomerular filtration can be increased by some medications, such as calcium channel blockers¹¹

Associated conditions 

• Risk factors include congestive heart failure, diabetes, sleep apnea, leg oedema, nephrosis, kidney failure, hypoalbuminemia, and abnormalities in circadian rhythm and sleep^12,13
• Reduced nocturnal bladder capacity: Conditions like bladder overactivity, benign prostatic hyperplasia, and interstitial cystitis limit the bladder's ability to store urine overnight, resulting in frequent urination
• Combination of nocturnal polyuria and reduced bladder capacity: This condition combines greater nighttime urine production with decreased bladder capacity, worsening the effects of nocturia
• Global polyuria refers to increased urine production over 24 hours, which can be caused by diabetes or excessive fluid intake¹⁴
• Sleep disorders sleep apnea: Causes intermittent hypoxia and increased secretion of atrial natriuretic peptide (ANP), which promotes excessive urine production
• Insomnia and other sleep disorders: Disrupted sleep patterns cause frequent nightly awakenings and increased urination¹⁵

Specific mechanisms in elderly

• Catecholamines and hypertension: Increased nighttime catecholamine levels in the elderly disrupt the normal circadian rhythm, leading to higher nocturnal urine production. Elevated catecholamine levels decrease blood flow through the kidney during the day and increase it at night, enhancing nocturnal urine production¹⁴
• BNP and heart function: Brain Natriuretic Peptide (BNP) levels increase with age and heart failure severity, promoting diuresis and vasodilation. BNP correlates with nocturnal urine volume, indicating its role in nocturnal polyuria¹⁶

Reduced Nocturnal Bladder Capacity

Reduced nocturnal bladder capacity is a key factor in nocturia, where the bladder's ability to hold urine at night is compromised. In healthy individuals, the volume of urine left after urination in the morning is usually 1.5 to 2 times that during the day, but this increase is not observed in those with nocturia.¹⁵

Mechanisms and contributing factors

• Hypertension
  • Elevated circulating catecholamines reduce the threshold bladder volume that triggers the urge to urinate by acting on the spinal adrenergic α1D receptor and bladder α1D receptor
  • Patients with morning hypertension often experience frequent urination before and after waking due to elevated blood pressure and catecholamine levels^17,18
• Sleep disorders
  • Aging reduces melatonin secretion, leading to decreased slow-wave and REM sleep, increased arousal, and early morning awakenings, thus lowering sleep efficiency
  • Slow-wave sleep lowers the arousal threshold in response to the need to urinate, causing frequent awakenings and nocturia¹⁹
• Neurotransmitter involvement
  • Low serum glycine levels, found in conditions like spinal cord injury and benign prostatic hyperplasia, may reduce bladder capacity. Glycine inhibits the micturition reflex, and decreased levels may lead to frequent urination
  • Flavoxate hydrochloride, which activates spinal glycinergic neurons, shows potential as a treatment for nocturia²⁰
• Irreversible organic changes
  • Prolonged reduced bladder capacity due to conditions like overactive bladder, encephalomyelopathy, voiding habits, tumours, or kidney stones can lead to permanent bladder capacity reduction

Management and treatment strategies for nocturia

A comprehensive strategy is required to effectively manage nocturia, including behavioural and lifestyle adjustments, medication, addressing underlying causes, and, if necessary, surgical measures. Each approach aims to enhance general quality of life and minimise the incidence of nocturnal urination.²¹

Behavioural and lifestyle modifications

• Fluid restriction
  • Evening fluid intake: Limiting fluid intake in the evening helps reduce the amount of urine produced at night. Patients are advised to drink more fluids earlier in the day
  • Types of fluids: Avoiding diuretics like caffeine and alcohol in the late afternoon and evening can also help
• Dietary changes
  • Salt intake: Reducing salt intake can help decrease fluid retention and, subsequently, nocturnal urine production
  • Balanced diet: Maintaining a healthy, balanced diet supports overall urinary health
• Timed voiding
  • Scheduled toileting: Encouraging patients to empty their bladders at regular intervals throughout the day and just before bedtime can help reduce nocturnal episodes
  • Bladder training: Techniques to gradually increase the interval between voids during the day can help improve bladder capacity and control

Pharmacological treatments

Table No. 1: Mechanism of action of pharmacological therapy.^21,22

Specific treatment with causes

Alpha-blockers such as tamsulosin and alfuzosin relax the smooth muscle fibres in the bladder neck and prostate gland, improving urine flow and reducing nocturnal voiding episodes, particularly beneficial for men with benign prostatic hyperplasia (BPH). 

Beta-3 adrenergic agonists like mirabegron increase bladder capacity by relaxing the detrusor muscle, thereby reducing the urgency to urinate and decreasing nocturia.

Phosphodiesterase-5 inhibitors such as tadalafil are used in men with BPH and nocturia to relax both bladder muscles and prostate tissue, alleviating symptoms. 

Combining different medications, such as antimuscarinics with alpha-blockers, can synergistically improve nocturia management by targeting multiple underlying causes simultaneously, enhancing overall treatment effectiveness and patient outcomes.^22,23,24

Summary

Effectively managing nocturia involves using minimally invasive, cost-effective methods to accurately diagnose underlying causes such as nocturnal polyuria, reduced bladder capacity, and systemic conditions. Physicians should adopt flexible and proactive treatment strategies, including lifestyle modifications, pharmacological therapies, and patient education. Continuous monitoring allows for timely adjustments to treatment, ensuring it remains tailored to the patient's evolving needs. This comprehensive approach not only aims to reduce the frequency of nocturnal urination but also significantly enhances the patient's physical and mental quality of life and daily functioning.