Association of phthalate exposure with precocious and delayed pubertal timing in girls and boys: a systematic review and meta-analysis

Exposure to phthalate derivatives has adverse effects on the health and development of humans, especially for children. A growing body of evidence supports the idea that exposure to phthalates can change an individual's physiological set point and the time of puberty in both genders. In this systematic review and meta-analysis, recent studies were evaluated to obtain systematic and regulation results in relation to puberty status and phthalate exposure in girls and boys. We searched English-language papers using Scopus, ISI, and PubMed databases as search engines, with no restriction of time, until the end of July 2019. A comprehensive literature search for an association between phthalate exposure and signs of puberty as well as levels of different types of hormones was carefully performed. Of the 67 studies retained for full-text screening, 39 studies were eligible for data management and extraction. For conducting a meta-analysis, four studies had appropriate effect size and metrics for pooling in the meta-analysis. Our findings revealed that low and high exposure to phthalates could alter pubertal development in both genders; the effects were either early or delayed puberty such as changes in the pubarche, thelarche, and menarche time, as well as in testicular volume. We statistically analyzed the association of pubic-hair development, breast development, and menarche time with exposure to phthalates in girls. For example, the pooled odds ratios of mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) in relation to breast development were (OR: 1.48, 95% CI: 1.11-1.85) and (OR: 1.52, 95% CI: 1.15-1.58) (P-value < 0.001), respectively. In addition, we analyzed the correlation between pubic-hair development and testicular volume with exposure to phthalates in boys. To the best of our knowledge, this is the first systematic review and meta-analysis of its kind for girls and boys. In conclusion, we found that a positive association exists between phthalate exposure and pubertal timing in the pediatric age group. Therefore, prevention of exposure to phthalates and reduction of their use should be underscored in the strategies for primordial prevention of pubertal timing and related consequences.