Foetal Exposure to Phthalates and Endocrine Effects on the Leydig Cell

This review examines the association between early life exposure to phthalates in human males and Leydig cell endocrine function. A systematic search was performed in PubMed and EMBASE, identifying 17 studies for analysis. Association scores weighted for number of phthalates and subjects were calculated for luteinizing hormone (LH), testosterone, testosterone/LH ratio and insulin-like factor 3 (INSL3). The scores ranges from full consistency of positive (score = 1), through inconsistent (score = 0), to negative/inverse (score = -1) associations. LH and early life phthalate exposure showed a statistically significant weighted phthalate association score of 0.18. Testosterone showed largely null results, whereas testosterone/LH ratio showed a negative association, both not statistically significant. A rise in LH, and decrease of testosterone/LH ratio, indicates that early life phthalate exposure results in a demand for a larger LH stimulus to produce the same amount of testosterone, and perhaps a decreased function of the Leydig cells, that manifests with the onset of high testosterone production in puberty and adulthood. A statistically non-significant decrease in INSL3 with a weighted phthalate association score of -0.29 supports this finding. An early life phthalate exposure-induced decline in Leydig cell function could possibly impact the spermatogenesis and adult male fertility.