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  • Human data are from very short-term and relatively short-term treatment studies that were not designed to examine safety. Few studies included children.

  • Many of the available studies in humans included small numbers of participants and varied greatly in duration of treatment, from a single dose to dosing for a few weeks or months.

  • Few investigators described systematic collection of adverse effects in clinical trials.

  • There is uncertainty in the dose-response relationship for adverse effects.

  • The risk of harm from doses greater than 10 mg/day is unknown.

D. Data Gaps and Future Research Recommended

  • All future clinical trials should include systematic collection and evaluation of adverse effects.

  • Dose-dependent safety studies in adults and children are needed. These studies should include investigations of the potential for harm in individuals taking more than 10 mg of melatonin per day.

  • The literature should continue to be monitored for signs of melatonin effects on tumors and testes.

  • The long-term safety of melatonin use in adults and children needs further study. These studies should include close monitoring of individuals with cardiovascular disease, specifically hypotension.

  • More information is needed concerning possible interactions between melatonin and drugs, particularly various cardiovascular, psychotropic, and anticonvulsant drugs.


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Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. 2002. Melatonin administration alters semen quality in healthy men. J Androl 23:572–578.

Ninomiya T, Iwatani N, Tomoda A, Miike T. 2001. Effects of exogenous melatonin on pituitary hormones in humans. Clin Physiol 21:292–299.

Okatani Y, Sagara Y. 1993. Role of melatonin in nocturnal prolactin secretion in women with normoprolactinemia and mild hyperprolactnemia. Am J Obstet Gynecol 168:854–861.

Pawlikowski M, Kolomecka M, Wojtczak A, Karasek M. 2002. Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women. Neuroendocrinol Lett 23:17–19.

Reiter RJ. 1991. Pineal gland: Interface between the photoperiodic environment and the endocrine system. Trends Endocrinol Metab 2:13–19.

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