Evidence-Based Hormone Therapies

164 placebo-controlled studies on the effect of melatonin on sleep (143 in adults)

Adults

1. Mousavi SS, Shohrati M, Vahedi E, Abdollahpour-Alitappeh M, Panahi Y. Effect of Melatonin Administration on Sleep Quality in Sulfur Mustard Exposed Patients with Sleep Disorders. Iran J Pharm Res. 2018 Winter;17(Suppl):136-144.
2. Vij V, Dahiya D, Kaman L, Behera A. Efficacy of melatonin on sleep quality after laparoscopic cholecystectomy. Indian J Pharmacol. 2018 Sep-Oct;50(5):236-241.
3. Cheikh M, Hammouda O, Gaamouri N, Driss T, Chamari K, Cheikh RB, Dogui M, Souissi N. Melatonin ingestion after exhaustive late-evening exercise improves sleep quality and quantity, and short-term performances in teenage athletes. Chronobiol Int. 2018 Sep;35(9):1281-1293
4. Kamoun A, Hammouda O, Yahia A, Dhari O, Ksentini H, Driss T, Souissi N, Elleuch MH. Effects of melatonin ingestion before nocturnal sleep on postural balance and subjective sleep quality in older adults. J Aging Phys Act. 2018 Aug 30:1-27.
5. Sletten TL, Magee M, Murray JM, Gordon CJ, Lovato N, Kennaway DJ, Gwini SM, Bartlett DJ, Lockley SW, Lack LC, Grunstein RR, Rajaratnam SMW; Delayed Sleep on Melatonin (DelSoM) Study Group. Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: a double-blind, randomised clinical trial. PLoS Med. 2018 Jun 18;15(6):e1002587.
6. Grima NA, Rajaratnam SMW, Mansfield D, Sletten TL, Spitz G, Ponsford JL. Efficacy of melatonin for sleep disturbance following traumatic brain injury: a randomised controlled trial. BMC Med. 2018 Jan 19;16(1):8.
7. Kurdi MS, Muthukalai SP. The efficacy of oral melatonin in improving sleep in cancer patients with insomnia: a randomized double-blind placebo-controlled study. Indian J Palliat Care. 2016 Jul-Sep;22(3):295-300.
8. Baandrup L, Glenthøj BY, Jennum PJ. Objective and subjective sleep quality: melatonin versus placebo add-on treatment in patients with schizophrenia or bipolar disorder withdrawing from long-term benzodiazepine use. Psychiatry Res. 2016 Jun 30;240:163-169.
9. Madsen MT, Hansen MV, Andersen LT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gögenur I. Effect of melatonin on sleep in the perioperative period after breast cancer surgery: a randomized, double-blind, placebo-controlled trial. J Clin Sleep Med. 2016 Feb;12(2):225-33.
10. Chojnacki C, Walecka-Kapica E, Klupinska G, Pawlowicz M, Blonska A, Chojnacki J. Effects of fluoxetine and melatonin on mood, sleep quality and body mass index in postmenopausal women. J Physiol Pharmacol. 2015 Oct;66(5):665-71.
11. Madsen MT, Hansen MV, Andersen LT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gögenur I. Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Sleep Med. 2015 Sep 14. pii: jc-00009-15.
12. Leonardo-Mendonça RC, Martinez-Nicolas A, de Teresa Galván C, Ocaña-Wilhelmi J, Rusanova I, Guerra-Hernández E, Escames G, Acuña-Castroviejo D. The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes. Chronobiol Int. 2015;32(8):1125-34.
13. Huang HW, Zheng BL, Jiang L, Lin ZT, Zhang GB, Shen L, Xi XM. Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation? Crit Care. 2015 Mar 19;19:124.
14. Roth T, Nir T, Zisapel N. Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial. Nat Sci Sleep. 2015 Jan 29;7:13-23.
15. Hansen MV, Madsen MT, Andersen LT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gögenur I. Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. Int J Breast Cancer. 2014;2014:416531.
16. Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014 Jun 18;9:947-61.
17. Spong J, Kennedy GA, Tseng J, Brown DJ, Armstrong S, Berlowitz DJ. Sleep disruption in tetraplegia: a randomised, double-blind, placebo-controlled crossover trial of 3 mg melatonin. Spinal Cord. 2014 Aug;52(8):629-34.
18. Chen WY, Giobbie-Hurder A, Gantman K, Savoie J, Scheib R, Parker LM, Schernhammer ES. A randomized, placebo-controlled trial of melatonin on breast cancer survivors: impact on sleep, mood, and hot flashes. Breast Cancer Res Treat. 2014 Jun;145(2):381-8. doi: 10.1007/s10549-014-2944-4
19. Burke TM, Markwald RR, Chinoy ED, Snider JA, Bessman SC, Jung CM, Wright KP Jr. Combination of light and melatonin time cues for phase advancing the human circadian clock. Sleep. 2013 Nov 1;36(11):1617-24
20. Schwertner A, Conceição Dos Santos CC, Costa GD, Deitos A, de Souza A, de Souza IC, Torres IL, da Cunha Filho JS, Caumo W. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013 Jun;154(6):874-81
21. Saxvig IW, Wilhelmsen-Langeland A, Pallesen S, Vedaa O, Nordhus IH, Bjorvatn A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: effects on subjective and objective sleep. Chronobiol Int.  2014 Feb;31(1):72-86.
22. Wilhelmsen-Langeland A, Saxvig IW, Pallesen S, Nordhus IH, Vedaa Ø, Lundervold AJ, Bjorvatn B. A randomized controlled trial with bright light and melatonin for the treatment of delayed sleep phase disorder: effects on subjective and objective sleepiness and cognitive function. J Biol Rhythms. 2013 Oct;28(5):306-21.
23. Edalat-Nejad M, Haqhverdi F, Hossein-Tabar T, Ahmadian M. Melatonin improves sleep quality in hemodialysis patients. Indian J Nephrol. 2013 Jul;23(4):264-9.
24. Spong J, Kennedy GA, Brown DJ, Armstrong SM, Berlowitz DJ. Melatonin supplementation in patients with complete tetraplegia and poor sleep. Sleep Disord. 2013;2013:128197.
25. Russcher M, Koch BC, Nagtegaal JE, van Ittersum FJ, Pasker-de Jong PC, Hagen EC, van Dorp WT, Gabreëls B, Wildbergh TX, van der Westerlaken MM, Gaillard CA, Ter Wee PM. Long-term effects of melatonin on quality of life and sleep in haemodialysis patients (Melody study): a randomized controlled trial. Br J Clin Pharmacol. 2013 Nov;76(5):668-79.
26. Halvani A, Mohsenpour F, Nasiriani K. Evaluation of exogenous melatonin administration in improvement of sleep quality in patients with chronic obstructive pulmonary disease. 2013;12(2):9-15
27. Vidor LP, Torres IL, Custódio de Souza IC, Fregni F, Caumo W. Analgesic and sedative effects of melatonin in temporomandibular disorders: a double-blind, randomized, parallel-group, placebo-controlled study. J Pain Symptom Manage. 2013 Sep;46(3):422-32
28. Scheer FA, Morris CJ, Garcia JI, Smales C, Kelly EE, Marks J, Malhotra A, Shea SA. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. 2012 Oct 1;35(10):1395-402.
29. Crowley SJ, Eastman CI. Melatonin in the afternoons of a gradually advancing sleep schedule enhances the circadian rhythm phase advance. Psychopharmacology (Berl). 2013 Feb;225(4):825-37. doi: 10.1007/s00213-012-2869-8.
30. Lemoine P, Wade AG, Katz A, Nir T, Zisapel N. Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials. Integr Blood Press Control. 2012;5:9-17.
31. Garfinkel D, Zorin M, Wainstein J, Matas Z, Laudon M, Zisapel N. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study. Diabetes Metab Syndr Obes. 2011;4:307-13.
32. Wade AG, Crawford G, Ford I, McConnachie A, Nir T, Laudon M, Zisapel N. 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 Jan;27(1):87-98.
33. Paul MA, Gray GW, Lieberman HR, Love RJ, Miller JC, Trouborst M, Arendt J. Phase advance with separate and combined melatonin and light treatment. Psychopharmacology (Berl). 2011 Mar;214(2):515-23.
34. Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, Zisapel N. 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 Aug 16;8:51.
35. Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res. 2010 Dec;19(4):591-6.
36. Burgess HJ, Revell VL, Molina TA, Eastman CI. Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. J Clin Endocrinol Metab. 2010 Jul;95(7):3325-31.
37. Borazan H, Tuncer S, Yalcin N, Erol A, Otelcioglu S. Effects of preoperative oral melatonin medication on postoperative analgesia, sleep quality, and sedation in patients undergoing elective prostatectomy: a randomized clinical trial. J Anesth. 2010 Apr;24(2):155-60.
38. Rahman SA, Kayumov L, Shapiro CM. Antidepressant action of melatonin in the treatment of Delayed Sleep Phase Syndrome. Sleep Med. 2010 Feb;11(2):131-6(Melatonin treatment significantly reduced depression scores in the depressed patients as measured by the CES-D and Hamilton Depression Rating Scale–17.
39. de Castro-Silva C, de Bruin VM, Cunha GM, Nunes DM, Medeiros CA, de Bruin PF. Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis–a randomized, double-blind placebo-controlled study. J Pineal Res. 2010 Jan;48(1):65-71.
40. Braam W, Didden R, Maas AP, Korzilius H, Smits MG, Curfs LM. Melatonin decreases daytime challenging behaviour in persons with intellectual disability and chronic insomnia. J Intellect Disabil Res. 2010 Jan 1;54(1):52-9.
41. Rahman SA, Kayumov L, Shapiro CM. Antidepressant action of melatonin in the treatment of Delayed Sleep Phase Syndrome. Sleep Med. 2010 Feb;11(2):131-13642.
42. Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009 Sep;24(5):239-4943.
43. Van Den Heuvel CJ, Kennaway DJ, Dawson D. Effects of daytime melatonin infusion in young adults. Am J Physiol. 1998 Jul;275(1 Pt 1):E19-26
44. Lushington K, Pollard K, Lack L, Kennaway DJ, Dawson D. Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency. Sleep. 1997 Dec;20(12):1135-4445.
45. Mishima K, Satoh K, Shimizu T, Hishikawa Y. Hypnotic and hypothermic action of daytime-administered melatonin. Psychopharmacology (Berl). 1997 Sep;133(2):168-71 46.
46. Krauchi K, Cajochen C, Wirz-Justice A. A relationship between heat loss and sleepiness: effects of postural change and melatonin administration. J Appl Physiol. 1997 Jul;83(1):134-947.
47. Hughes RJ, Badia P. Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep. 1997 Feb;20(2):124-3148.
48. Reid K, Van den Heuvel C, Dawson D. Day-time melatonin administration: effects on core temperature and sleep onset latency. J Sleep Res. 1996 Sep;5(3):150-449.
49. Nave R, Herer P, Haimov I, Shlitner A, Lavie P. Hypnotic and hypothermic effects of melatonin on daytime sleep in humans: lack of antagonism by flumazenil. Neurosci Lett. 1996 Aug 23;214(2-3):123-650.
50. Cajochen C, Krauchi K, von Arx MA, Mori D, Graw P, Wirz-Justice A. Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking EEG. Neurosci Lett. 1996 Apr 5;207(3):209-13

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Higher quality of life, energy: the improvement with melatonin treatment (23 references)

1. Gilard V, Ferracci FX, Langlois O, Derrey S, Proust F, Curey S. Effects of melatonin in the treatment of asthenia in aneurysmal subarachnoid hemorrhage. 2016 Dec;62(6):295-299.
2. Datieva VK, Rosinskaia AV, Levin OS. The use of melatonin in the treatment of chronic fatigue syndrome and circadian rhythm disorders in parkinson’s disease. Zh Nevrol Psikhiatr Im S S Korsakova. 2013;113(7 Pt 2):77-81.
3. Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009 Sep;24(5):239-49
4. Zisapel N. [Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs] Harefuah. 2009 May;148(5):337-41, 348
5. Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N. Efficacy of prolonged relase melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007 Oct;23(10):2597-605

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Higher mood: the association with higher melatonin levels (22 references)

1. Bumb JM, Enning F, Mueller JK, van der List T, Rohleder C, Findeisen P, Noelte I, Schwarz E, Leweke FM. Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder. Compr Psychiatry. 2016 Jul;68:34-9.
2. Sundberg I, Ramklint M, Stridsberg M, Papadopoulos FC, Ekselius L, Cunningham JL. Salivary Melatonin in Relation to Depressive Symptom Severity in Young Adults. PLoS One. 2016 Apr 4;11(4):e0152814.
3. Obayashi K, Saeki K, Iwamoto J, Tone N, Tanaka K, Kataoka H, Morikawa M, Kurumatani N. Physiological levels of melatonin relate to cognitive function and depressive symptoms: the heijo-kyo cohort. J Clin Endocrinol Metab. 2015 Aug;100(8):3090-6.
4. Meliska CJ, Martínez LF, López AM, Sorenson DL, Nowakowski S, Kripke DF, Elliott J, Parry BL. Antepartum depression severity is increased during seasonally longer nights: relationship to melatonin and cortisol timing and quantity. Chronobiol Int. 2013 Nov;30(9):1160-73.
5. Khaleghipour S, Masjedi M, Ahade H, Enayate M, Pasha G, Nadery F, Ahmadzade G. Morning and nocturnal serum melatonin rhythm levels in patients with major depressive disorder: an analytical cross-sectional study. Sao Paulo Med J. 2012;130(3):167-72.

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Depression: the improvement with melatonin treatment (8 references)

1. Hansen MV, Andersen LT, Madsen MT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gögenur I. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial. Breast Cancer Res Treat. 2014 Jun;145(3):683-95.
2. Rahman SA, Kayumov L, Shapiro CM. Antidepressant action of melatonin in the treatment of Delayed Sleep Phase Syndrome. Sleep Med. 2010 Feb;11(2):131-6
3. Zisapel N. Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs Harefuah. 2009 May;148(5):337-41, 348
4. Jean-Louis G, von Gizycki H, Zizi F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res 1998 Oct;25(3):177-83
5. Raghavendra V, Kaur G, Kulkarni SK. Anti-depressant action of melatonin in chronic forced swimming-induced behavioral despair in mice, role of peripheral benzodiazepine receptor modulation. Eur Neuropsychopharmacol. 2000 Dec;10(6):473-81

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Calmness, serenity: the association with higher melatonin levels (1 reference)

1. McIntyre IM, Judd FK, Marriott PM, Burrows GD, Norman TR. Plasma melatonin levels in affective states. Int J Clin Pharmacol Res; 1989;9(2):159-64

Anxiety: the improvement with melatonin treatment (13 references)

1. Javaherforooshzadeh F, Amirpour I, Janatmakan F, Soltanzadeh M. Comparison of effects of melatonin and gabapentin on postoperative anxiety and pain in lumbar spine surgery: a randomized clinical trial. Anesth Pain Med. 2018 Jun 24;8(3):e68763.
2. Ghaeli P, Solduzian M, Vejdani S, Talasaz AH. Comparison of the effects of melatonin and oxazepam on anxiety levels and sleep quality in patients with st-segment-elevation myocardial infarction following primary percutaneous coronary intervention: a randomized clinical trial. Ann Pharmacother. 2018 Oct;52(10):949-955.
3. Impellizzeri P, Vinci E, Gugliandolo MC, Cuzzocrea F, Larcan R, Russo T, Gravina MR, Arena S1, D’Angelo G, Gitto E, Montalto AS, Alibrandi A, Marseglia L, Romeo C. Premedication with melatonin vs midazolam: efficacy on anxiety and compliance in paediatric surgical patients. Eur J Pediatr. 2017 Jul;176(7):947-953.
4. Kurdi MS, Muthukalai SP. A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomized double-blind study. Indian J Anaesth. 2016 Oct;60(10):744-750.
5. Marseglia L, Manti S, D’Angelo G, Arrigo T, Cuppari C, Salpietro C, Gitto E. Potential use of melatonin in procedural anxiety and pain in children undergoing blood withdrawal. J Biol Regul Homeost Agents. 2015 Apr-Jun;29(2):509-14.

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Memory loss, cognitive impairment: the association with low melatonin levels (4 references)

1. Waller KL, Mortensen EL, Avlund K, Fagerlund B, Lauritzen M, Gammeltoft S, Jennum P. Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition. Nat Sci Sleep. 2016 Jan 21;8:47-53.
2. Sirin FB, Kumbul Doğuç D, Vural H, Eren I, Inanli I, Sütçü R, Delibaş N. Plasma 8-isoPGF2α and serum melatonin levels in patients with minimal cognitive impairment and Alzheimer disease. Turk J Med Sci. 2015;45(5):1073-7.
3. Kulesh AA, Shestakov VV. Secretion of melatonin and serum cholinesterase activity as biological markers of cognitive disorders in the acute stage of ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova. 2012;112(12 Pt 2):11-4.
4. Obayashi K, Saeki K, Iwamoto J, Tone N, Tanaka K, Kataoka H, Morikawa M, Kurumatani N. Physiological levels of melatonin relate to cognitive function and depressive symptoms: The heijo-kyo cohort. J Clin Endocrinol Metab. 2015 Aug;100(8):3090-6.

Memory loss, cognitive impairment: the improvement with melatonin treatment (7 references)

1. Roostaei T, Sahraian MA, Hajeaghaee S, Gholipour T, Togha M, Siroos B, Mansouri S, Mohammadshirazi Z, Aghazadeh Alasti M, Harirchian MH. Impact of melatonin on motor, cognitive and neuroimaging indices in patients with multiple sclerosis. Iran J Allergy Asthma Immunol. 2015 Dec;14(6):589-95.
2. Foster PS, Campbell RW, Williams MR, Branch KK, Roosa KM, Orman C, Drago V. Administration of exogenous melatonin increases spreading activation in lexical memory networks. Hum Psychopharmacol. 2014 Jul;29(4):397-404.
3. Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014 Jun 18;9:947-61.
4. Cardinali DP, Vigo DE, Olivar N, Vidal MF, Furio AM, Brusco LI. Therapeutic application of melatonin in mild cognitive impairment. Am J Neurodegener Dis. 2012;1(3):280-91.
5. Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2011 Jul;26(7):687-94..

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Alzheimer’s disease, dementia: the association with lower melatonin levels (4 references)

1. Mishima K, Okawa M, Hishikawa Y, Hozumi S, Hori H, Takahashi K. Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia. Acta Psychiatr Scand. 1994 Jan;89(1):1-7
2. Tohgi H, Abe T, Takahashi S, Kimura M, Takahashi J, Kikuchi T. Concentrations of serotonin and its related substances in the cerebrospinal fluid in patients with Alzheimer type dementia. Neurosci Lett. 1992 Jul 6;141(1):9-12
3. Luboshitzky R, Shen-Orr Z, Tzischichinsky O, Maldonado M, Herer P, Lavie P. Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer’s disease. Chronobiol Int. 2001 May;18(3):513-24
4. Ozcankaya R, Delibas N. Malondialdehyde, superoxide dismutase, melatonin, iron, copper, and zinc blood concentrations in patients with Alzheimer disease: cross-sectional study. Croat Med J. 2002 Feb;43(1):28-32

Alzheimer’s disease: the improvement with melatonin treatment (2 references)

1. Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease
2. Wang JZ, Wang ZF. Role of melatonin in Alzheimer-like neurodegeneration. Acta Pharmacol Sin. 2006 Jan;27(1):41-9

Sleep disorders: the association with lower melatonin levels (6 references)

1. Rahman SA, Marcu S, Kayumov L, Shapiro CM. Altered sleep architecture and higher incidence of subsyndromal depression in low endogenous melatonin secretors. Eur Arch Psychiatry Clin Neurosci. 2010
2. Blaicher W, Speck E, Imhof MH, Gruber DM, Schneeberger C, Sator MO, Huber JC. Melatonin in postmenopausal females. Arch Gynecol Obstet. 2000 Feb;263(3):116-8
3. Riemann D, Klein T, Rodenbeck A, Feige B, Horny A, Hummel R, Weske G, Al-Shajlawi A, Voderholzer U. Nocturnal cortisol and melatonin secretion in primary insomnia. Psychiatry Res. 2002 Dec 15;113(1-2):17-27
4. Rodenbeck A, Huether G, Ruther E, Hajak G. Nocturnal melatonin secretion and its modification by treatment in patients with sleep disorders. Adv Exp Med Biol. 1999;467:89-93
5. Hajak G, Rodenbeck A, Staedt J, Bandelow B, Huether G, Ruther E. Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia. J Pineal Res. 1995 Oct;19(3):116-22

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Erectile dysfunction: the association with low melatonin levels (1 reference)

1. Bozkurt A, Karabakan M, Aktas BK, Gunay M, Keskin E, Hirik E. Low serum melatonin levels are associated with erectile dysfunction. Int Braz J Urol. 2018 Jul-Aug;44(4):794-799.

Erectile dysfunction: the improvement with melatonin treatment in rats (3 references)

1. Zhang JL, Hui Y, Zhou F, Hou JQ. Neuroprotective effects of melatonin on erectile dysfunction in streptozotocin-induced diabetic rats. Int Urol Nephrol. 2018 Nov;50(11):1981-1988.
2. Tavukçu HH, Sener TE, Tinay I, Akbal C, Erşahin M, Cevik O, Cadirci S, Reiter RJ, Sener G. Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats. Clin Exp Pharmacol Physiol. 2014 Apr;41(4):309-16.
3. Qiu XF, Li XX, Chen Y, Lin HC, Yu W, Wang R, Dai YT. Mobilisation of endothelial progenitor cells: one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats. Asian J Androl. 2012 May;14(3):481-6.

Premature ejaculation: the association with low melatonin levels (1 reference)

1. Kirecci SL, Simsek A, Gurbuz ZG, Mimaroglu S, Yuksel A, Vural P, Degirmencioglu S. Relationship between plasma melatonin levels and the efficacy of selective serotonin reuptake inhibitors treatment on premature ejaculation. Int J Urol. 2014 Sep;21(9):917-20.

Delayed sexual maturation: the association with melatonin treatment in rodents (8 references)

1. Carlson LL, Zimmermann A, Lynch GR. Geographic differences for delay of sexual maturation in peromyscus leucopus: effects of photoperiod, pinealectomy, and melatonin. Biol Reprod. 1989 Dec;41(6):1004-13.
2. Aubert ML, Rivest RW, Lang U, Winiger BP, Sizonenko PC. Delayed sexual maturation induced by daily melatonin administration eliminates the LH response to naloxone despite normal responsiveness to GnRH in juvenile male rats. Neuroendocrinology. 1988 Jul;48(1):72-80.
3. Laudon M, Yaron Z, Zisapel N. N-(2,4-dinitrophenyl)-5-methoxytryptamine, a novel melatonin antagonist: effects on sexual maturation of the male and female rat and on oestrous cycles of the female rat [corrected]. J Endocrinol. 1988 Jan;116(1):43-53.
4. Lang U, Aubert ML, Rivest RW, Vinas-Bradtke JC, Sizonenko PC. Inhibitory action of exogenous melatonin, 5-methoxytryptamine, and 6-hydroxymelatonin on sexual maturation of male rats: activity of 5-methoxytryptamine might be due to its conversion to melatonin. Biol Reprod. 1985 Oct;33(3):618-28.
5. Lang U, Aubert ML, Rivest RW, Vinas-Bradtke JC, Sizonenko PC. Daily afternoon administration of melatonin does not irreversibly inhibit sexual maturation in the male rat. Endocrinology. 1984 Dec;115(6):2303-10.

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Precocious puberty: caused by neonatal melatonin treatment in male and female rats (2 references)

1. Esquifino AI, Villanúa MA, Agrasal C. Effect of neonatal melatonin administration on sexual development in the rat. J Steroid Biochem. 1987;27(4-6):1089-93.
2. Moreno ML, Villanúa MA, Esquifino AI. Serum prolactin and luteinizing hormone levels and the activities of hypothalamic monoamine oxidase A and B and phenylethanolamine-N-methyl transferase are changed during sexual maturation in male rats treated neonatally with melatonin. J Pineal Res. 1992 Nov;13(4):167-73.

Hypercholesterolemia: the association with lower melatonin levels (1 reference)

1. Sandyk R, Awerbuch GI. The relationship between melatonin secretion and serum cholesterol in patients with multiple sclerosis. Int J Neurosci. 1994 May;76(1-2):81-6

Hypercholesterolemia and hypertriglyceridemia: the improvement with melatonin treatment (review study) (1 reference)

1. Mohammadi-Sartang M, Ghorbani M, Mazloom Z. Effects of melatonin supplementation on blood lipid concentrations: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr. 2018 Dec;37(6 Pt A):1943-1954.

Hypercholesterolemia and hyperhomocysteinemia: the improvement with melatonin treatment in rats (2 references)

1. Sewerynek E. Melatonin and the cardiovascular system. Neuroendocrinol Lett. 2002 Apr;23 Suppl 1:79-83
2. Murawska-Cialowicz E, Januszewska L, Zuwala-Jagiello J, Milczarska J, Zawadzki M, Paprocka-Borowicz M, Wierzbicka-Damska I. Melatonin decreases homocysteine level in blood of rats. J Physiol Pharmacol. 2008 Dec;59(4):717-29

Atherosclerosis: the association with lower melatonin levels (3 references)

1. Tikhomirova OV, Zybina NN, Bobko OV, Frolova MY. The clinical/laboratory support for using melatonin in chronic cerebrovascular diseases and metabolic syndrome. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(12):44-48
2. Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia MJ, Sanchez J, Marrero F, de Armas-Trujillo D. Decreased nocturnal melatonin levels during acute myocardial infarction. J Pineal Res. 2002 Nov;33(4):248-52
3. Girotti L, Lago M, Ianovsky O, Carbajales J, Elizari MV, Brusco LI, Cardinali DP. Low urinary 6-sulphatoxymelatonin levels in patients with coronary artery disease. J Pineal Res. 2000 Oct;29(3):138-42

Atherosclerosis: the improvement with melatonin treatment in rabbits (1 reference)

1. Hu ZP, Fang XL, Fang N, Wang XB, Qian HY, Cao Z, Cheng Y, Wang BN, Wang Y. Melatonin ameliorates vascular endothelial dysfunction, inflammation, and atherosclerosis by suppressing the TLR4/NF-κB system in high-fat-fed rabbits. J Pineal Res. 2013 Nov;55(4):388-98.

Arterial hypertension: the association with lower melatonin levels (6 references)

1. Cui HW, Zhang ZX, Gao MT, Liu Y, Su AH, Wang MY. Circadian rhythm of melatonin and blood pressure changes in patients with essential hypertension. Zhonghua Xin Xue Guan Bing Za Zhi. 2008 Jan;36(1):20-3
2. Zeman M, Dulková K, Bada V, Herichová I. Plasma melatonin concentrations in hypertensive patients with the dipping and non-dipping blood pressure profile. Life Sci. 2005 Mar 4;76(16):1795-803
3. Cagnacci A, Arangino S, Angiolucci M, Melis GB, Tarquini R, Renzi A, Volpe A. Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy. J Pineal Res. 2000 Oct;29(3):152-8
4. Rapoport SI, Shatalova AM, Malinovskaia NK, Vettenberg L. Melatonin production in hypertensive patients. Klin Med (Mosk). 2000;78(6):21-4
5. Rapoport SI, Shatalova AM, Oraevskii VN, Malinovskaia NK, Vetterberg L. Melatonin production in hypertonic patients during magnetic storms. Ter Arkh. 2001;73(12):29-33

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Hypertension: the improvement with melatonin treatment (20 references)

1. Shao G, Zhang S, Nie J, Li J, Tong J. Effects of melatonin on mechanisms involved in hypertension using human umbilical vein endothelial cells. J Toxicol Environ Health A. 2017;80(23-24):1342-1348.
2. Maarman GJ. Natural antioxidants as potential therapy, and a promising role for melatonin against pulmonary hypertension. Adv Exp Med Biol. 2017;967:161-178.
3. Rechciński T, Trzos E, Wierzbowska-Drabik K, Krzemińska-Pakuła M, Kurpesa M. Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability. Hypertens Res. 2010 Jan;33(1):56-61
4. Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens. 2009 Aug;27 Suppl 6:S17-20.
5. Zaslavskaia RM, Shcherban’ EA, Logvinenko SI. Melatonin in combined therapy of patients with stable angina and arterial hypertension. Klin Med (Mosk). 2008;86(9):64-7.

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Cardiac disease: the association with lower melatonin levels (7 references)

1. Ballyuzek MF, Mashkova MV, Arutjunyan AV, Duke VA. Melatonin as a marker of the grade of cardiac disorders during cachexia development in oncological patients of different ages. Adv Gerontol. 2017;30(1): 70-77.
2. Rodriguez MI, Escames G, López LC, García JA, Ortiz F, López A, Acuña-Castroviejo D. Melatonin administration prevents cardiac and diaphragmatic mitochondrial oxidative damage in senescence-accelerated mice. J Endocrinol. 2007 Sep;194(3):637-43
3. Sahna E, Deniz E, Aksulu HE. Myocardial ischemia-reperfusion injury and melatonin.Anadolu Kardiyol Derg. 2006 Jun;6(2):163-8
4. Marktl W, Brugger P, Herold M. Melatonin and coronary heart disease. Wien Klin Wochenschr. 1997 Oct 3;109(18):747-9
5. Brugger P, Marktl W, Herold M. Impaired nocturnal secretion of melatonin in coronary heart disease. Lancet. 1995 Jun 3;345(8962):1408

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Coronary heart disease (myocardial infarction):  the association with low melatonin levels (1 reference)

1. McMullan CJ, Rimm EB, Schernhammer ES, Forman JP. A nested case-control study of the association between melatonin secretion and incident myocardial infarction. 2017 May;103(9):694-701.

Coronary heart disease, cardiac morbidity: the improvement with melatonin treatment (2 references)

1. Shafiei E, Bahtoei M, Raj P, Ostovar A, Iranpour D, Akbarzadeh S, Shahryari H, Anvaripour A, Tahmasebi R, Netticadan T, Movahed A. Effects of N-acetyl cysteine and melatonin on early reperfusion injury in patients undergoing coronary artery bypass grafting: A randomized, open-labeled, placebo-controlled trial. Medicine (Baltimore). 2018 Jul;97(30):
2. Dwaich KH, Al-Amran FG, Al-Sheibani BI, Al-Aubaidy HA. Melatonin effects on myocardial ischemia-reperfusion injury: Impact on the outcome in patients undergoing coronary artery bypass grafting surgery. Int J Cardiol. 2016 Oct 15;221:977-86.

Coronary heart disease:  the improvement with melatonin treatment (animal studies) (5 references)

1. Feng J, Chen X, Liu R, Cao C, Zhang W, Zhao Y, Nie S. Melatonin protects against myocardial ischemia-reperfusion injury by elevating Sirtuin3 expression and manganese superoxide dismutase activity. Free Radic Res. 2018 Aug;52(8):840-9.
2. Yu L, Li B, Zhang M, Jin Z, Duan W, Zhao G, Yang Y, Liu Z, Chen W, Wang S, Yang J, Yi D, Liu J, Yu S. Melatonin reduces PERK-eIF2α-ATF4-mediated endoplasmic reticulum stress during myocardial ischemia-reperfusion injury: role of RISK and SAFE pathways interaction. Apoptosis. 2016 Jul;21(7):809-24.
3. Gögenur I, Kücükakin B, Panduro Jensen L, Reiter RJ, Rosenberg J. Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair: a randomized, placebo-controlled, clinical trial. J Pineal Res. 2014 Aug;57(1):10-5.
4. Lee YM, Chen HR, Hsiao G, Sheu JR, Wang JJ, Yen MH. Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. J Pineal Res. 2002 Sep;33(2):72-80
5. Dave RH, Hale SL, Kloner RA. The effect of melatonin on hemodynamics, blood flow, and myocardial infarct size in a rabbit model of ischemia-reperfusion. J Cardiovasc Pharmacol Ther. 1998 Apr;3(2):153-160

Heart failure: the improvement with melatonin treatment (animal study) (1 reference)

1. Liskova IuV, Salikova SP, Stadnikov AA. Structural reorganization of the myocardium in ovariectomized rats with experimental heart failure after melatonin administration. 2013;144(5):25-9.

Obesity: the association with lower melatonin levels (7 references)

1. Tikhomirova OV, Zybina NN, Bobko OV, Frolova MY. The clinical/laboratory support for using melatonin in chronic cerebrovascular diseases and metabolic syndrome. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(12):44-48.
2. Walecka-Kapica E, Chojnacki J, Stępień A, Wachowska-Kelly P, Klupińska G, Chojnacki C. Melatonin and female hormone secretion in postmenopausal overweight women. Int J Mol Sci. 2015 Jan 5;16(1):1030-42.
3. Sato M, Kanikowska D, Iwase S, Shimizu Y, Nishimura N, Inukai Y, Sato M, Sugenoya J. Seasonal differences in melatonin concentrations and heart rates during sleep in obese subjects in Japan. Int J Biometeorol. 2013 Sep;57(5):743-8.
4. No authors listed. Relationship between insulin, leptin, and melatonin contents in patients with metabolic syndrome. Klin Med (Mosk). 2011;89(6):46-9.
5. Blaicher W, Imhof MH, Gruber DM, Schneeberger C, Sator MO, Huber JC. Endocrinological disorders. Focusing on melatonin’s interactions. Gynecol Obstet Invest. 1999;48(3):179-82

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Obesity: the improvement with melatonin treatment (10 references)

1. Sun H, Wang X, Chen J, Gusdon AM, Song K, Li L, Qu S. Melatonin treatment improves insulin resistance and pigmentation in obese patients with acanthosis nigricans. Int J Endocrinol. 2018 Mar 12;2018:2304746.
2. Szewczyk-Golec K, Rajewski P, Gackowski M, Mila-Kierzenkowska C, Wesołowski R, Sutkowy P, Pawłowska M, Woźniak A. Melatonin supplementation lowers oxidative stress and regulates adipokines in obese patients on a calorie-restricted diet. Oxid Med Cell Longev. 2017;2017:8494107.
3. Goyal A, Terry PD, Superak HM, Nell-Dybdahl CL, Chowdhury R, Phillips LS, Kutner MH. Melatonin supplementation to treat the metabolic syndrome: a randomized controlled trial. Diabetol Metab Syndr. 2014 Nov 18;6:124.
4. Koziróg M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011 Apr;50(3):261-6.
5. Hussein MR, Ahmed OG, Hassan AF, Ahmed MA. Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model. Int J Exp Pathol. 2007 Feb;88(1):19-29

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Type 1 diabetes: the association with low melatonin levels (1 reference)

1. Kor Y, Geyikli I, Keskin M, Akan M. Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus. Indian J Endocrinol Metab. 2014 Jul;18(4):565-8.

Type 1 diabetes: the association with high melatonin levels in rats, but increased levels in type 2 diabetes (2 references)

1. Peschke E, Hofmann K, Pönicke K, Wedekind D, Mühlbauer E. Catecholamines are the key for explaining the biological relevance of insulin-melatonin antagonisms in type 1 and type 2 diabetes. J Pineal Res. 2012 May;52(4):389-96.
2. Peschke E, Hofmann K, Bähr I, Streck S, Albrecht E, Wedekind D, Mühlbauer E. The insulin-melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus). 2011 Jul;54(7):1831-40.