Sex Differences in Serum Prolactin Levels in Children and Adolescents on Antipsychotics: A Systematic Review and Meta-Analysis

Background: Serum prolactin levels are influenced by sex, physical development and medications among other factors. Antipsychotics usually increase serum prolactin levels in both adults and younger patients, but no study has reviewed the potential association between sex and vulnerability for developing hyperprolactinemia among children and adolescents. Objective: Systematic review and meta-analysis of serum prolactin levels in children and adolescents on antipsychotic treatment for any psychiatric diagnosis to determine the effect of sex. Methods: A systematic search was performed in MEDLINE/PubMed/Web of Science and Cochrane databases for randomized controlled trials of antipsychotics in children and adolescents reporting serum prolactin levels by sex. Results: Of 1278 identified records, seven studies were included, comparing different single antipsychotics to placebo (risperidone N=4; lurasidone N=1; olanzapine N=1; queriapine N=1). Both male and female children and adolescents on antipsychotics presented a significant increase in prolactin levels relative to subjects receiving a placebo. (Male: 16.53 with 95% CI: 6.15-26.92; Female: 26.97 with 95% CI: 9.18-44.75). The four studies using risperidone had similar findings (Male: 26.49 with 95% CI: 17.55-35.43; Female: 37.72 with 95% CI: 9.41-66.03). In the direct comparison between sexes, females showed greater increases in prolactin, but the differences were not statistically significant. Conclusion: Serum prolactin levels are increased in children and adolescents of both sexes on antipsychotics, with females showing a slightly greater increase than males. Further research is needed to clarify the influence of sex and pubertal status on prolactin levels in children and adolescents taking antipsychotics.