Reproductive safety of melatonin: a "wonder drug" to wonder about

By some accounts, melatonin is the wonder drug of the 1990s. This previously obscure hormone came to the public's full attention as the result of a series of popular books claiming therapeutic benefits of melatonin ingestion. Some of these claims deserve serious consideration and investigation, whereas others appear unfounded. Without waiting for the outcome of the ongoing scientific debate, however, melatonin set astounding sales records. The hormone is now ingested on a daily basis by many thousands of people. There is little information on the potential adverse effects of melatonin ingestion in humans. Melatonin, its analogs, and its metabolites are not mutagenic, and melatonin possesses remarkably low acute toxicity in animals and humans. It is more difficult to exclude toxic effects of long-term melatonin treatment. The fact that melatonin is normally secreted each night does not ensure that exogenous melatonin, taken at other times and/or in supraphysiological doses, will not have adverse effects. Despite the well-recognized role of melatonin in the regulation of reproduction in photoperiodic species, it seems unlikely that chronic ingestion of moderate melatonin doses will have a profound impact on reproductive function in humans. Evidence that melatonin modulates steroid hormone action in some steroid-responsive tissues suggests that these tissues should be carefully examined when attempting to assess whether melatonin has chronic toxicity in humans. In the absence of sufficient information regarding the longterm safety of exogenous melatonin, the conservative course of action is to restrict melatonin use to those therapeutic applications in which a significant benefit is expected. The decision to ingest melatonin should be preceded by careful consideration of the expected benefits as well as the potential costs of treatment, with recognition of the fact that there has been exaggeration of the benefits and little attention paid to the potential costs in most discussions of this issue to date.