Serotonergic polymorphisms in the control of ejaculation.

Serotonin has long been implicated in the regulation of the processes that trigger the ejaculatory reflex. Most evidence of serotonergic involvement is, however, indirect, stemming either from studies on rodents or clinical trials investigating effects of serotonergic drugs. In the past decade, emerging evidence for heritability (i.e., genetic effects) of premature ejaculation (PE) symptoms has spawned a number of scholarly attempts to identify genes that regulate ejaculation, most of which have focused on candidate genes related to the serotonergic system. The aim of the present review article was to summarize the literature concerning genetic association studies of PE, with focus on serotonergic genes. However, methodological obstacles relating to the candidate gene approach predict that a priori hypotheses regarding candidate genes are likely to generate ambiguous and spurious results if samples (e.g., if samples are underpowered and/or stratified). Attempts to replicate reported novel associations between PE symptoms and serotonergic candidate genes have largely failed (thereby adding to the growing body of evidence casting doubt on the reliability of the candidate gene approach), and at present, it is not possible to determine with acceptable certainty which serotonergic genes, if any, are involved in ejaculatory function.