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

Ulla Nordström Joensen,¹ Hanne Frederiksen,¹ Martin Blomberg Jensen,¹ Mette Petri Lauritsen,² Inge Ahlmann Olesen,¹ Tina Harmer Lassen,¹ Anna-Maria Andersson,¹ and Niels Jørgensen¹

¹Department of Growth and Reproduction, and ²Fertility Department, Copenhagen University Hospital, Copenhagen, Denmark


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.


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.


Key words: DEHP, DiNP, male reproduction, phthalates, semen quality, testosterone, %MEHP, %MiNP. 


Environ Health Perspect 120:1397–1403 (2012). http://dx.doi.org/10.1289/ehp.1205113 [Online 24 July 2012]


Address correspondence to U.N. Joensen, Department of Growth and Reproduction, Copenhagen University Hospital, section 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Telephone: 45 3545 5064. Fax: 45 3545 6054. E-mail: ulla.nordstroem.joensen@rh.regionh.dk


We thank all participants; we also thank O. Nielsen for skilled technical assistance. 


The authors received financial support from the European Commission (DEER, FP7-2007-212844), the Danish Agency for Science, Technology and Innovation (grants 27107068 and 09-067180), the University Hospital of Copenhagen (grant 961506336), the University of Copenhagen, the Danish Ministry of Health, the Danish Environmental Protection Agency (MST-621-00013), and the Kirsten and Freddy Johansen Foundation (grant 95-103-72087). Instrumental equipment was supported financially by the Velux Foundation. 


The funding organizations played no role in the design and conduct of the study, in collection, management, analysis, and interpretation of the data; or in the presentation, review, or approval of the manuscript.


The authors declare they have no actual or potential competing financial interests.


Received 17 February 2012; Accepted 23 July 2012; Online 24 July 2012.