title: Associations between serum phthalates and biomarkers of reproductive function in 589 adult men.
abstract: Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level. Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant inverse associations between serum levels of the metabolites, the proxies and serum testosterone. Negative associations were also discovered between some metabolites and sex hormone-binding globulin, semen volume and total sperm count. Findings are compatible with a weak anti-androgenic action of DEHP metabolites, but less so for DiNP metabolites. Metabolic pathways differed significantly between the three study sites, but without major effect on semen quality or reproductive hormones.
authors.affiliation: Department of Occupational and Environmental Medicine, University Hospital of Copenhagen, DK-2400 Copenhagen NV, Denmark. Electronic address: ina.olmer.specht@regionh.dk.
authors.forename: Ina Olmer
authors.initials: IO
authors.lastname: Specht
authors.affiliation: Department of Occupational Medicine, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. Electronic address: gunntoft@rm.dk.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
authors.affiliation: National Research Centre for the Working Environment, DK-2100 Copenhagen Ø, Denmark. Electronic address: ksh@arbejdsmiljoforskning.dk.
authors.forename: Karin S
authors.initials: KS
authors.lastname: Hougaard
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, SE-221 85 Lund, Sweden. Electronic address: christian.lindh@med.lu.se.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Lindh
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, NL-3584 CM Utrecht, The Netherlands. Electronic address: V.C.Lenters@uu.nl.
authors.forename: Virissa
authors.initials: V
authors.lastname: Lenters
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, SE-221 85 Lund, Sweden. Electronic address: bo_a.jonsson@med.lu.se.
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, NL-3584 CM Utrecht, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.affiliation: Reproductive Medicine Centre, Malmö University Hospital, Lund University, Malmö SE-20502, Sweden. Electronic address: aleksander.giwercman@med.lu.se.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.affiliation: Department of Occupational and Environmental Medicine, University Hospital of Copenhagen, DK-2400 Copenhagen NV, Denmark. Electronic address: Jens.Peter.Ellekilde.Bonde@regionh.dk.
authors.forename: Jens Peter E
authors.initials: JP
authors.lastname: Bonde
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D004051:Diethylhexyl Phthalate / Q000097:blood* / Q000633:toxicity; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity; D042341:Gonadal Hormones / Q000097:blood*; D006116:Greenland; D006801:Humans; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids / Q000097:blood* / Q000633:toxicity; D011044:Poland; D012661:Semen / Q000187:drug effects; D055101:Semen Analysis; D013223:Statistics as Topic; D014455:Ukraine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D042341:Gonadal Hormones; D010795:Phthalic Acids; C012125:diisononyl phthalate; D004051:Diethylhexyl Phthalate
keywords: Di-2-ethylhexyl phthalate; Diisononyl phthalate; Fertility; Metabolic pathway; Reproduction; Testosterone