Associations between serum phthalates and biomarkers of reproductive function in 589 adult men

TY - JOUR

T1 - Associations between serum phthalates and biomarkers of reproductive function in 589 adult men

AU - Specht, Ina Olmer

AU - Toft, Gunnar

AU - Hougaard, Karin S

AU - Lindh, Christian H

AU - Lenters, Virissa

AU - Jönsson, Bo A G

AU - Heederik, Dick

AU - Giwercman, Aleksander

AU - Bonde, Jens Peter E

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/5

Y1 - 2014/5

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Biological Markers

KW - Diethylhexyl Phthalate

KW - Environmental Pollutants

KW - Gonadal Hormones

KW - Greenland

KW - Humans

KW - Male

KW - Middle Aged

KW - Phthalic Acids

KW - Poland

KW - Semen

KW - Semen Analysis

KW - Statistics as Topic

KW - Ukraine

KW - Young Adult

U2 - 10.1016/j.envint.2014.02.002

DO - 10.1016/j.envint.2014.02.002

M3 - Journal article

C2 - 24583187

SN - 0160-4120

VL - 66

SP - 146

EP - 156

JO - Environment International

JF - Environment International

ER -