Low melatonin levels are associated with an increased likelihood of nocturia in elderly individuals, according to a Japanese study.

“Enhancing endogenous melatonin levels may be a preventive and therapeutic option for nocturia,” researchers concluded.

Kenji Obayashi, MD, and collaborators at Nara Medical University School of Medicine in Nara, conducted a cross-sectional study that enrolled 861 community-dwelling elderly individuals who had a mean age of 72 years. The investigators measured subjects’ nocturnal void frequency and overnight urinary 6-sulfatoxymelatonin excretion (UME), a marker for melatonin secretion.

Continue Reading

Of the 861 subjects, 261 suffered from nocturia—defined as two or more nocturnal voids—and 600 did not. After adjusting for confounding factors, Dr. Obayashi’s group found that higher UME levels were significantly associated with a decreased likelihood for nocturia. An increase in URE from 4.0 to 10.0 μg (from the 25th to 75th percentile) was associated with a 24.7% decrease in prevalent nocturia, the researchers reported online ahead of print in The Journal of Urology.

In addition, in adjusted analyses, the mean volume of single voided urines increased significantly with tertiles of UME.

“To the best of our knowledge, our results provide the first evidence that endogenous melatonin is significantly and inversely associated with nocturia independent of confounding factors in a general elderly population with a large sample of males and females,” the authors wrote.

In analyzing their findings, the researchers adjusted for age, gender, body mass index, estimated glomerular filtration rate, benign prostatic hyperplasia, duration in bed, and other potential confounders.

Secretion of melatonin, a pineal gland hormone, follows a diurnal rhythm, with almost all production at night, Dr. Obayashi’s team explained. “Endogenous melatonin has inhibitory effects on smooth muscle contractility of the mammalian bladder. Thus, melatonin may play a key role in nocturnal regulation of voids.”

Previous clinical studied have suggested that exogenous melatonin or its agonist decreases nocturia episodes. For example, a placebo-controlled study of melatonin treatment for nocturia in men with benign prostatic hyperplasia found that oral administration of 2 mg of controlled-release melatonin at night was associated with a significant nocturia response rate and improvement in nocturia-related bother, according to a report in The Journal of Urology (2004;171:1199-1202). The melatonin also had a good adverse effect profile. “However, it is uncertain whether the observed changes in this study are clinically significant,” the researchers concluded.

In another study, researchers at the University of the Ryukyus in Okinawa, Japan randomized 42 elderly patients with nocturia to receive either melatonin 2 mg/day (20 patients) or rilmazafone 2 mg/day (22 patients). After four weeks of treatment, the number of nocturnal urinations was significantly decreased and quality-of-life significantly improved in both groups, investigators reported in The Journal of International Medical Research (2007;35:685-691). Patient-reported effectiveness ratings did not differ significantly between treatment arms. The serum melatonin level increased significantly in the melatonin recipients, but remained unchanged in the rilmazafone-treated group, “suggesting that the decrease of nocturnal urination after treatment with rilmazafone did not depend on serum melatonin level,” the authors noted.