Effectiveness of melatonin for the treatment of nocturia: a randomized controlled trial

Leerasiri, Pichai; Pariyaeksut, Pimchanok; Hengrasmee, Pattaya; Asumpinwong, Chutimon

doi:10.1007/s00192-022-05232-3

Cited by 10 publications

(21 citation statements)

References 27 publications

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“…Furthermore, night serum melatonin level in elderly persons with nocturia is lower than those without 20 . Importantly, melatonin treatment significantly decreased nocturnal urination frequency and improved quality of life 20 , 53 . In the aged bladder, accumulation of reactive oxidative species is significantly augmented 58 as well as stretch-induced firing of low threshold bladder afferents 59 , which may be responsible for development of lower urinary tract symptoms in the elderly.…”

Section: Discussionmentioning

confidence: 98%

Melatonin inhibits muscular-mucosal stretch-sensitive bladder afferents via the MT2 receptors

Ramsay

Zagorodnyuk

2022

Sci Rep

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Melatonin is a circadian rhythm regulator capable of controlling a variety of physiological processes in the body. It predominantly acts via the melatonin 1 (MT1) and MT2 receptors expressed in the CNS neurons and peripheral organs and tissues. Melatonin can modulate urinary bladder function, however, to date it is not known if melatonin can regulate activity of sensory neurons innervating the bladder. Bladder afferents play an important role in urine storage and voiding. Therefore, this study aims to determine if melatonin can regulate mechanosensitivity of 2 major classes of sensory neurons in the guinea pig bladder: stretch-insensitive mucosal and low threshold stretch-sensitive muscular-mucosal afferents. The effects of melatonin on the mechanosensitivity of mucosal and muscular-mucosal afferents were measured ex vivo using single unit extracellular recording. Melatonin did not affect the responses of mucosal afferents to stroking of their receptive fields but did concentration-dependently, significantly inhibit 69% of muscular-mucosal afferents responses to stroking and bladder stretch. This inhibitory effect was not affected by the MT1 receptor antagonist, S26131 but was blocked by the selective MT2 receptor antagonists, K-185 and 4-P-PDOT. Forskolin significantly potentiated the responses of muscular-mucosal afferents to stroking and stretch, which were prevented by melatonin. These findings demonstrate a direct inhibitory effect of melatonin on the mechanosensitivity of low threshold stretch-sensitive muscular-mucosal bladder afferents acting via MT2 receptors, which is independent from its action on detrusor muscle. This may have important clinical implications for the treatment of many common bladder disorders including nocturia.

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Section: Discussionmentioning

confidence: 98%

Melatonin inhibits muscular-mucosal stretch-sensitive bladder afferents via the MT2 receptors

Ramsay

Zagorodnyuk

2022

Sci Rep

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“…Around 10% of men with nocturia reported using medications to help their sleep ( Table 1 ). Considering its influence on circadian rhythms, which is a known factor for lower urinary symptoms (LUS), a recent randomized, controlled trial suggested the therapeutic effects of melatonin on nocturia [ 30 ]. This effectiveness could be due to the increase in bladder capacity and decrease in urine volume, as demonstrated in rats treated with melatonin [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Predictive Values of Nocturia and Its Voiding Frequency on the Aging Males’ Symptoms

Yuen

Wong

Chiu

et al. 2022

IJERPH

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Background: The link between nocturia and aging male symptoms (AMS) has not been scientifically established. This study aimed to measure the degree of severity of AMS that impacts health-related quality of life (HRQoL) in adult males living with nocturia and to determine the predictive values of nocturnal factors on AMS. Methods: This is an extended analysis of new data collected by using the Hong Kong Traditional AMS (HK-AMS) scale and the Cantonese version of the Pittsburgh Sleep Quality Index (PSQI) in a recently published cross-sectional population-based survey. Results: Of the 781 respondents that completed the set of questionnaires, 68% and 61% of men living with nocturia reported clinically significant (at moderate-to-severe levels) somato-vegetative and sexual AMS; the prevalence and severity were increased with advancing nighttime voiding frequency. Age, the Global PSQI score, certain metabolic diseases, the nocturia-specific QoL (NQoL) score and bedtime voiding frequency were found to be significant predictive factors for composite somato-vegetative and sexual AMS. Conclusions: The current findings suggested the inclusion of nocturia when measuring male-specific HRQoL related to aging.

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“…Three double-blinded randomized control trials compared melatonin treatment to placebo. Two 17,18 studied 2 mg extended-release melatonin in a double-blind crossover study and one 16 with 2 mg nonextended release in a noncrossover study. The male and female patients with statistically significant nocturia improvement had baseline nocturia in the absence of existing neurologic conditions, 16,18 shown in a cross-over and noncrossover study, without similar improvement of symptoms with placebo.…”

Section: Placebo Controlled Trialsmentioning

confidence: 99%

Melatonin and melatonin receptor agonists in the treatment of nocturia: A systematic review

Burke,

Nitti,

Stothers

2024

Neurourology and Urodynamics

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AimCauses of nocturia may extend beyond primary bladder pathology and it has been commonly associated as a side effect of sleep disorders. This has led to the study of melatonin and melatonin receptor agonists as a primary treatment for nocturia hypothesized to be secondary to sleep disorders. We aim to systematically review the efficacy and reported safety of melatonin and melatonin receptor agonists in the treatment of nocturia.MethodsA search strategy of EMBASE and Pubmed/Medline databases was utilized to identify eligible studies. Two thousand and twenty‐eight unique references were identified in concordance with the Preferred Reporting Items of Systematic Reviews and Meta‐Analyses guidelines for systematic reviews, of which nine papers met the inclusion criteria. The Cochrane Collaboration risk of bias criteria in the open label and nonplacebo studies was used to assess bias.ResultsThe nine studies identified included 3 randomized double‐blinded placebo‐controlled trials, 2 randomized non‐placebo trial, and 4 prospective open‐label trials. Three utilized the melatonin‐receptor agonist ramelteon (8 mg) and six utilized melatonin (four 2 mg extended release, two 2 mg normal release). Nocturia improved in 8 studies varying from moderate to low efficacy related to reduction in nocturia episodes. Five studies evaluated sleep parameters finding improvement in both nocturia and sleep quality. Male subjects represented 76.8% of 371 total subjects in prospective and randomized trials. Ramelteon and melatonin were both reported as well tolerated during nocturia treatment. A meta‐analysis was not able to be performed due to the heterogeneity of bladder diagnoses.ConclusionsAt this time, there is insufficient evidence to routinely recommend melatonin as an effective treatment for nocturia given the limitations of current clinical studies. Randomized placebo‐controlled trials and prospective open label studies in non‐neurogenic populations report a trend towards nocturia improvement with good tolerability and rare side effects. Therefore, further larger scale randomized trials with focused urologic diagnoses in well‐characterized patient populations are warranted.

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Effectiveness of melatonin for the treatment of nocturia: a randomized controlled trial

Cited by 10 publications

References 27 publications

Melatonin inhibits muscular-mucosal stretch-sensitive bladder afferents via the MT2 receptors

Melatonin inhibits muscular-mucosal stretch-sensitive bladder afferents via the MT2 receptors

Predictive Values of Nocturia and Its Voiding Frequency on the Aging Males’ Symptoms

Melatonin and melatonin receptor agonists in the treatment of nocturia: A systematic review

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