title: Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men.
abstract: BACKGROUND
  In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function.
  
  
  OBJECTIVE
  We aimed to provide estimates of the effects of phthalate exposure on reproductive hormone levels and semen quality in healthy men.
  
  
  METHODS
  A total of 881 men gave urine, serum, and semen samples. Serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-B; semen quality; and urinary concentrations of 14 phthalate metabolites, including metabolites of di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP), were assessed. The proportions of DEHP and DiNP excreted as their respective primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-isononyl phthalate (MiNP)] were calculated and expressed as percentages (%MEHP and %MiNP, respectively).
  
  
  RESULTS
  The free androgen index was 15% lower [95% confidence interval (CI): -23, -8%] for men in the highest %MiNP quartile compared to the lowest quartile (p < 0.001) after adjusting for confounders, and 9% lower (95% CI: -16, -1%) in the highest %MEHP quartile (p = 0.02). %MEHP and %MiNP were negatively associated with the ratio of testosterone/LH and testosterone/FSH. %MEHP was negatively associated with total testosterone, free testosterone, and ratio of testosterone/E(2). %MiNP was positively associated with SHBG. There was little evidence of associations between urinary phthalate metabolites or sums of phthalates with reproductive hormones or semen quality.
  
  
  CONCLUSIONS
  Our data suggest that both testosterone production and pituitary-hypothalamic feedback may be compromised in individuals excreting a high proportion of primary metabolites of long-chained phthalates relative to the proportion of secondary metabolites.
authors: Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark. ulla.nordstroem.joensen@rh.regionh.dk
authors: Ulla Nordström
authors: UN
authors: Joensen
authors: Hanne
authors: H
authors: Frederiksen
authors: Martin
authors: M
authors: Blomberg Jensen
authors: Mette Petri
authors: MP
authors: Lauritsen
authors: Inge Ahlmann
authors: IA
authors: Olesen
authors: Tina Harmer
authors: TH
authors: Lassen
authors: Anna-Maria
authors: AM
authors: Andersson
authors: Niels
authors: N
authors: Jørgensen
mesh_terms: D000293:Adolescent; D002853:Chromatography, Liquid; D003718:Denmark; D004781:Environmental Exposure; D004784:Environmental Monitoring; D042341:Gonadal Hormones / Q000097:blood*; D006065:Gonadotropins, Pituitary / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D008297:Male; D010795:Phthalic Acids / Q000652:urine*; D055101:Semen Analysis; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D042341:Gonadal Hormones; D006065:Gonadotropins, Pituitary; D010795:Phthalic Acids; D012738:Sex Hormone-Binding Globulin