The effect of melatonin treatment on postural stability, muscle strength, and quality of life and sleep in postmenopausal women: a randomized controlled trial

Anne Kristine Amstrup, Tanja Sikjaer, Leif Mosekilde, Lars Rejnmark, Anne Kristine Amstrup, Tanja Sikjaer, Leif Mosekilde, Lars Rejnmark

Abstract

Background: Melatonin is often used as a sleeping aid in elderly adults. As previous studies suggest a protective role of melatonin against osteoporosis, it is important to document its safety. Treatment should not cause any hangover effect that could potentially lead to falls and fractures. We therefore aimed to evaluate the effect of melatonin on balance- and muscle function.

Methods and patients: In a double-blind placebo-controlled study, we randomized 81 postmenopausal women with osteopenia to receive 1 or 3 mg melatonin, or placebo nightly for 12 months. Postural balance as well as muscle function was measured. In addition, we assessed quality of life and sleep at baseline and after 12 months treatment.

Results: Compared to placebo, one-year treatment with melatonin did not affect postural balance or risk of falls. Furthermore, no significant changes between groups were observed in muscle strength in neither upper- nor lower extremities. Treatment did not affect quality of life or sleep. However, in the subgroup of women with sleep disturbances at baseline, a trend towards an improved sleep quality was seen (p = 0.08).

Conclusion: Treatment with melatonin is safe in postmenopausal women with osteopenia. There is no hangover effect affecting balance- and muscle function following the intake of melatonin. In women with a good quality of sleep, melatonin has no effect, however in poor quality of sleep, small doses of melatonin trended towards improving the quality.

Trial registration: (# NCT01690000).

Figures

Fig. 1
Fig. 1
Effects of treatment with placebo or melatonin on blood pressure and heart rate. Mean ± SD

References

    1. Stehle JH, Saade A, Rawashdeh O, Ackermann K, Jilg A, Sebesteny T, et al. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res. 2011;51:17–43. doi: 10.1111/j.1600-079X.2011.00856.x.
    1. Zhdanova IV, Wurtman RJ, Balcioglu A, Kartashov AI, Lynch HJ. Endogenous melatonin levels and the fate of exogenous melatonin: age effects. J Gerontol A Biol Sci Med Sci. 1998;53:B293–B298. doi: 10.1093/gerona/53A.4.B293.
    1. Maestroni GJ, Conti A, Pierpaoli W. Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol. 1986;13:19–30. doi: 10.1016/0165-5728(86)90047-0.
    1. Esteban S, Garau C, Aparicio S, Moranta D, Barcelo P, Fiol MA, et al. Chronic melatonin treatment and its precursor L-tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain. J Pineal Res. 2010;48:170–177. doi: 10.1111/j.1600-079X.2009.00741.x.
    1. Martinez-Campa C, Gonzalez A, Mediavilla MD, Alonso-Gonzalez C, Alvarez-Garcia V, Sanchez-Barcelo EJ, et al. Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells. Br J Cancer. 2009;101:1613–1619. doi: 10.1038/sj.bjc.6605336.
    1. Cagnacci A, Cannoletta M, Renzi A, Baldassari F, Arangino S, Volpe A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18:1614–1618. doi: 10.1016/j.amjhyper.2005.05.008.
    1. Histing T, Anton C, Scheuer C, Garcia P, Holstein JH, Klein M, et al. Melatonin impairs fracture healing by suppressing RANKL-mediated bone remodeling. J Surg Res. 2012;173:83–90. doi: 10.1016/j.jss.2010.08.036.
    1. Koyama H, Nakade O, Takada Y, Kaku T, Lau KH. Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res. 2002;17:1219–1229. doi: 10.1359/jbmr.2002.17.7.1219.
    1. Zang LY, Cosma G, Gardner H, Vallyathan V. Scavenging of reactive oxygen species by melatonin. Biochim Biophys Acta. 1998;1425:469–477. doi: 10.1016/S0304-4165(98)00099-3.
    1. Park KH, Kang JW, Lee EM, Kim JS, Rhee YH, Kim M, et al. Melatonin promotes osteoblastic differentiation through the BMP/ERK/Wnt signaling pathways. J Pineal Res. 2011;51:187–194. doi: 10.1111/j.1600-079X.2011.00875.x.
    1. Kanis JA, Melton LJ, III, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137–1141. doi: 10.1002/jbmr.5650090802.
    1. Amstrup AK, Sikjaer T, Heickendorff L, Mosekilde L, Rejnmark L. Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial. J Pineal Res. 2015;59:221–229. doi: 10.1111/jpi.12252.
    1. Ha H, Cho K, Lee W. Reliability of the good balance system ((R)) for postural sway measurement in poststroke patients. J Phys Ther Sci. 2014;26:121–124. doi: 10.1589/jpts.26.121.
    1. Tiainen K, Sipila S, Kauppinen M, Kaprio J, Rantanen T. Genetic and environmental effects on isometric muscle strength and leg extensor power followed up for three years among older female twins. J Appl Physiol. 2009;106:1604–1610. doi: 10.1152/japplphysiol.91056.2008.
    1. Curb JD, Ceria-Ulep CD, Rodriguez BL, Grove J, Guralnik J, Willcox BJ, et al. Performance-based measures of physical function for high-function populations. J Am Geriatr Soc. 2006;54:737–742. doi: 10.1111/j.1532-5415.2006.00700.x.
    1. Ware JE, Kosinski M, Bjoerner J, Turner-Bowker DM, Gandek B, Maruish ME: Scoring procedures. User’s Manual for the SF-36v2 Health Survey. ed 2nd, Lincon: RI: QualityMetric Incorporated, 2007;53-64
    1. de WM, Pouwer F, Gemke RJ, Delemarre-van de Waal HA, Snoek FJ. Validation of the WHO-5 Well-Being Index in adolescents with type 1 diabetes. Diabetes Care. 2007;30:2003–2006. doi: 10.2337/dc07-0447.
    1. Bjorner JB, Thunedborg K, Kristensen TS, Modvig J, Bech P. The Danish SF-36 Health Survey: translation and preliminary validity studies. J Clin Epidemiol. 1998;51:991–999. doi: 10.1016/S0895-4356(98)00091-2.
    1. Buysse DJ, Reynolds CF, III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Aadahl M, Jorgensen T. Validation of a new self-report instrument for measuring physical activity. Med Sci Sports Exerc. 2003;35:1196–1202. doi: 10.1249/01.MSS.0000074446.02192.14.
    1. Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int. 2000;66:419–424. doi: 10.1007/s002230010085.
    1. RAD Neurim Pharmaceuticals EEC Limited: Circadin, prolinged-release, Product information; 2007;Annex I: 1-27
    1. Fourtillan JB, Brisson AM, Fourtillan M, Ingrand I, Decourt JP, Girault J. Melatonin secretion occurs at a constant rate in both young and older men and women. Am J Physiol Endocrinol Metab. 2001;280:E11–E22.
    1. Markantonis SL, Tsakalozou E, Paraskeva A, Staikou C, Fassoulaki A. Melatonin pharmacokinetics in premenopausal and postmenopausal healthy female volunteers. J Clin Pharmacol. 2008;48:240–245. doi: 10.1177/0091270007311112.
    1. Waldhauser F, Waldhauser M, Lieberman HR, Deng MH, Lynch HJ, Wurtman RJ. Bioavailability of oral melatonin in humans. Neuroendocrinology. 1984;39:307–313. doi: 10.1159/000123997.
    1. Fraschini F, Cesarani A, Alpini D, Esposti D, Stankov BM. Melatonin influences human balance. Biol Signals Recept. 1999;8:111–119. doi: 10.1159/000014578.
    1. Otmani S, Metzger D, Guichard N, Danjou P, Nir T, Zisapel N, et al. Effects of prolonged-release melatonin and zolpidem on postural stability in older adults. Hum Psychopharmacol. 2012;27:270–276. doi: 10.1002/hup.2219.
    1. Atkinson G, Buckley P, Edwards B, Reilly T, Waterhouse J. Are there hangover-effects on physical performance when melatonin is ingested by athletes before nocturnal sleep? Int J Sports Med. 2001;22:232–234. doi: 10.1055/s-2001-16387.
    1. Edwards BJ, Atkinson G, Waterhouse J, Reilly T, Godfrey R, Budgett R. Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones. Ergonomics. 2000;43:1501–1513. doi: 10.1080/001401300750003934.
    1. Kotlarczyk MP, Lassila HC, O’Neil CK, D’Amico F, Enderby LT, Witt-Enderby PA, et al. Melatonin osteoporosis prevention study (MOPS): a randomized, double-blind, placebo-controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women. J Pineal Res. 2012;52:414–426. doi: 10.1111/j.1600-079X.2011.00956.x.
    1. Alstadhaug KB, Odeh F, Salvesen R, Bekkelund SI. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology. 2010;75:1527–1532. doi: 10.1212/WNL.0b013e3181f9618c.
    1. Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, et al. Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007;23:2597–2605. doi: 10.1185/030079907X233098.
    1. Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010;8:51. doi: 10.1186/1741-7015-8-51.
    1. Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898–902. doi: 10.1016/j.amjmed.2006.02.002.
    1. Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004;43:192–197. doi: 10.1161/01.HYP.0000113293.15186.3b.

Source: PubMed

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