Could long-term administration of melatonin to prepubertal children affect timing of puberty? A clinician's perspective

Exogenous melatonin can be used to treat sleep disturbance in adults, children, and adolescents. While its short-term use is considered safe, there are some concerns that long-term use might delay children's sexual maturation, possibly by disrupting the decline in nocturnal melatonin levels that occur at the onset of puberty. This narrative review aimed to summarize some of the current knowledge about the potential effects of exogenous melatonin on puberty. We found no clinical studies that experimentally tested the effects of melatonin on pubertal timing in children, but we reviewed the small number of observational studies. We also drew on animal data to try to answer our question. The photoperiod and melatonin-mediated seasonal transitions in sexual activity and breeding in some mammals across the seasons have been used as a model of sexual development in mammals, including humans. The switch from non-sexual activity (in the non-breeding period) to sexual activity (in the breeding period) has been likened to the onset of puberty as there are similarities between the two. We conclude that to investigate an association between melatonin and pubertal timing, it will be important to conduct long-term randomized controlled trials of latency age children and also examine the cellular and systems-level interactions between melatonin and kisspeptin, a recently identified neuropeptide with a locus of action at the gonadotropin releasing hormone neurons that is important in contributing to the timing of puberty onset.