222 Male reproductive toxicity of phthalates: a cross-sectional study of testosterone and total sperm count in European and Inuit populations

Abstract

Objectives Phthalates are widely used man-made chemicals that in spite of a short half-life in the organism are detectable in urine among more than 95% of investigated men and women. Phthalates are with varying potency anti-androgens through interaction with several metabolic steps involved in endogenous sex-steroid metabolism. Some cross-sectional studies have shown inverse associations between phthalates and plasma levels of testosterone and some semen characteristics, but the evidence base is limited and results are conflicting. The aim of this study was to examine the hypothesis that phthalates are associated with reduced levels of plasma testosterone and total sperm counts. Methods Spouses of pregnant women from Greenland (n = 196), Poland (n = 190) and Ukraine (n = 203) were enrolled into the study. We measured six metabolites of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DINP) in serum and concurrent testosterone, sperm concentration, sperm volume and total sperm count. Analyses were stratified by country as well as analysed across countries. Results The most abundant metabolite from DEHP namely 5-cx-MEPP (mean concentration in serum 2.22 ng/ml) was negatively associated with testosterone, sperm volume and total sperm count in the overall analysis after adjustment for country, age, sexual abstinence time and current smoking. Testosterone decreased with 1.08% pr ng/ml 5-cx-MEPP (p = 0.032), volume with 1.59% (p = 0.043) and total sperm count with 3.47% (p = 0.030). When analysed by country the association was strongest in Ukraine and Poland, but the inverse relationship between 5-cx-MEPP and outcomes was observed in all three countries. No significant association between phthalate metabolites and sperm concentration was observed. Conclusions These results are compatible with a weak anti-androgenic action of the DEHP metabolite 5-cx-MEPP on testosterone and total sperm count. Whether this cross-sectional association reflects causal mechanisms remains to be established.