Introduction and hypothesis
Nocturia affects health and quality of life (QoL). Current medical treatments can cause severe adverse effects, especially when treating elderly patients. Endogenous melatonin has a physiologic role in urinary bladder function, and the exogenous one may be beneficial for this condition. This article aims to evaluate the effectiveness and safety of melatonin for ameliorating nocturia in older women.
This randomized, double-blind, placebo-controlled trial was conducted at a university hospital in Thailand. Sixty women with nocturia, aged > 55 years, were prospectively recruited and were later randomly allocated to treatment (melatonin 2 mg/day, n = 30) and control (placebo, n = 30) arms for 2 weeks. Outcome measures included nocturia episodes, nocturia-related parameters, Nocturia Quality of Life Questionnaire (N-QoL) scores, and adverse events.
The treatment and control groups were comparable in mean age (65.9 + 7.5 vs. 68.5 + 6.3 years). Both groups had comparable causes of nocturia with a baseline median voiding frequency of 2.3 (1.3, 6.3) and 2.3 (1.7, 5.3) episodes/night, respectively. The treatment group had significantly better outcomes than the placebo group in terms of median reduction in nocturia [-1.0 (-3.0, 0.0) vs. 0.0 (-2.3, 1.3) episodes/night; p < 0.001], increased median duration of the first uninterrupted sleep [1.0 (-0.3, 4.5) vs. 0.0 (-3.0, 2.3) h; p < 0.001], and improvement in N-QoL scoring, especially in the sleep/energy subscale (p = 0.019) and the total score (p = 0.016). Adverse events were comparable between groups.
Melatonin can be considered a safe and effective treatment for nocturia in elderly women.
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Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61:37–49.
Tikkinen KA, Johnson TM, Tammela TL, Sintonen H, Haukka J, Huhtala H, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol. 2010;57:488–96.
Fitzgerald MP, Litman HJ, Link CL, McKinlay JB, Survey Investigators BACH. The association of nocturia with cardiac disease, diabetes, body mass index, age and diuretic use: results from the BACH survey. J Urol. 2007;177:1385–9.
Asplund R. Hip fractures, nocturia, and nocturnal polyuria in the elderly. Arch Gerontol Geriatr. 2006;43:319–26.
Parsons JK, Mougey J, Lambert L, Wilt TJ, Fink HA, Garzotto M, et al. Lower urinary tract symptoms increase the risk of falls in older men. BJU Int. 2009;104:63–8.
Temml C, Ponholzer A, Gutjahr G, Berger I, Marszalek M, Madersbacher S. Nocturia is an age-independent risk factor for hip-fractures in men. Neurourol Urodyn. 2009;28:949–52.
Nakagawa H, Niu K, Hozawa A, Ikeda Y, Kaiho Y, Ohmori-Matsuda K, et al. Impact of nocturia on bone fracture and mortality in older individuals: a Japanese longitudinal cohort study. J Urol. 2010;184:1413–8.
Lightner DJ, Krambeck AE, Jacobson DJ, McGree ME, Jacobsen SJ, Lieber MM, et al. Nocturia is associated with an increased risk of coronary heart disease and death. BJU Int. 2012;110:848–53.
Asplund R. Nocturia: consequences for sleep and daytime activities and associated risks. Eur Urol Suppl. 2005;3:24–32.
Udo Y, Nakao M, Honjo H, Ukimura O, Kawauchi A, Kitakoji H, et al. Analysis of nocturia with 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration: concept for effective treatment modality. BJU Int. 2011;107:791–8.
Udo Y, Nakao M, Honjo H, Ukimura O, Kitakoji H, Miki T. Sleep duration is an independent factor in nocturia: analysis of bladder diaries. BJU Int. 2009;104:75–9.
Negoro H, Kanematsu A, Yoshimura K, Ogawa O. Chronobiology of micturition: putative role of the circadian clock. J Urol. 2013;190:843–9.
Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336:186–95.
Fathollahi A, Daneshgari F, Hanna-Mitchell AT. Melatonin and its role in lower urinary tract function: An article review. Curr Urol. 2015;8:113–8.
Sugaya K, Nishijima S, Oda M, Owan T, Miyazato M, Ogawa Y. Biochemical and body composition analysis of nocturia in the elderly. Neurourol Urodyn. 2008;27:205–11.
Cornu JN, Abrams P, Chapple CR, Dmochowski RR, Lemack GE, Michel MC, et al. A contemporary assessment of nocturia: definition, epidemiology, pathophysiology, and management—a systematic review and meta-analysis. Eur Urol. 2012;62:877–90.
Obayashi K, Saeki K, Kurumatani N. Association between melatonin secretion and nocturia in elderly individuals: a cross-sectional study of the HEIJO-KYO cohort. J Urol. 2014;191:1816–21.
Wade AG, Crawford G, Ford I, McConnachie A, Nir T, Laudon M, et al. Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response. Curr Med Res Opin. 2011;27:87–98.
Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007;16:372–80.
Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346:541–4.
Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N. Melatonin replacement therapy of elderly insomniacs. Sleep. 1995;18:598–603.
Poeggeler B. Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy. Endocrine. 2005;27:201–12.
Drake MJ, Mills IW, Noble JG. Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J Urol. 2004;171:1199–202.
Sugaya K, Nishijima S, Miyazato M, Kadekawa K, Ogawa Y. Effects of melatonin and rilmazafone on nocturia in the elderly. J Int Med Res. 2007;35:685–91.
Dijk DJ, Cajochen C, Tobler I, Borbely AA. Sleep extension in humans: sleep stages, EEG power spectra and body temperature. Sleep. 1991;14:294–306.
Stanley N. The underestimated impact of nocturia on quality of life. Eur Urol Suppl. 2005;4:17–9.
Nowak JZ, Zawilska JB. Melatonin and its physiological and therapeutic properties. Pharm World Sci. 1998;20:18–27.
The authors gratefully acknowledge the women who generously agreed to participate in this study and Ms. Nerisa Thornsri, MSc of the Research Group and Research Network Division, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, for assistance with statistical analysis.
The study was funded by a grant from Siriraj Routine to Research (R2R), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Leerasiri, P., Pariyaeksut, P., Hengrasmee, P. et al. Effectiveness of melatonin for the treatment of nocturia: a randomized controlled trial. Int Urogynecol J 34, 485–492 (2023). https://doi.org/10.1007/s00192-022-05232-3