Phthalate Excretion Pattern and Testicular Function: A Study of 881 Healthy Danish Men

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. Objectives: We aimed to provide estimates of the effects of phthalate ex...

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Bibliographic Details
Published in:Environmental health perspectives 2012-10, Vol.120 (10), p.1397-1403
Main Authors: Joensen, Ulla Nordström, Frederiksen, Hanne, Jensen, Martin Blomberg, Lauritsen, Mette Petri, Olesen, Inge Ahlmann, Lassen, Tina Harmer, Andersson, Anna-Maria, Jørgensen, Niels
Format: Article
Language:English
Subjects:
Adolescent
Animal experimentation
Biological and medical sciences
Birth control
Chemical hazards
Chromatography, Liquid
Denmark
Environment. Living conditions
Environmental Exposure
Environmental Monitoring
Gonadal Hormones - blood
Gonadotropins, Pituitary - blood
Gynecology. Andrology. Obstetrics
Health aspects
Hormone metabolism
Hormones
Humans
Immunoassay
Male
Medical sciences
Men
Metabolites
Phthalates
Phthalic Acids - urine
Public health. Hygiene
Public health. Hygiene-occupational medicine
Quartiles
Reproductive health
Risk factors
Semen
Semen Analysis
Serums
Sex Hormone-Binding Globulin - analysis
Sexual disorders
Spermatozoa
Sterility. Assisted procreation
Tandem Mass Spectrometry
Testosterone
Toxicology
Urine
Young Adult
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Summary: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. Objectives: 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/E2. %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 Conclusion: 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.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.1205113