Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.
BACKGROUND
Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders.


OBJECTIVE
To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU).


METHODS
An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources.


RESULTS
The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion.


CONCLUSIONS
EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.
Department of Environmental Health (R.H.), Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115; Department of Growth and Reproduction (N.E.S., A.J., A.M.A.), Rigshospitalet, EDMaRC and University of Copenhagen, DK-2100 Copenhagen, Denmark; National Food Institute (U.H.), Technical University of Denmark, 2800 Kgs Søborg, Denmark; Departments of Physiology and Pediatrics (J.T.), University of Turku, 20014 Turku, Finland; Brunel University (A.K.), London UB8 3PH, United Kingdom; National Institute of Environmental Health Sciences (J.J.H.), Division of Extramural Research and Training, Research Triangle Park, North Carolina 27709; New York University (NYU) School of Medicine (L.T.), New York, New York 10016; NYU Wagner School of Public Service (L.T.), New York, New York 10012; NYU Steinhardt School of Culture, Education, and Human Development (L.T.), Department of Nutrition, Food, and Public Health, New York, New York 10003; and NYU Global Institute of Public Health (L.T.), New York, New York 10003.
Russ
R
Hauser
Niels E
NE
Skakkebaek
Ulla
U
Hass
Jorma
J
Toppari
Anders
A
Juul
Anna Maria
AM
Andersson
Andreas
A
Kortenkamp
Jerrold J
JJ
Heindel
Leonardo
L
Trasande
D000328:Adult; D057231:Climate Change; D017281:Cost of Illness; D003456:Cryptorchidism / Q000139:chemically induced / Q000191:economics / Q000453:epidemiology; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure / Q000191:economics / Q000706:statistics & numerical data; D005058:Eunuchism / Q000139:chemically induced / Q000191:economics / Q000453:epidemiology; D005062:European Union / Q000191:economics* / Q000706:statistics & numerical data; D006801:Humans; D007248:Infertility, Male / Q000139:chemically induced* / Q000191:economics* / Q000453:epidemiology; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000139:chemically induced / Q000191:economics / Q000453:epidemiology; D013736:Testicular Neoplasms / Q000139:chemically induced / Q000191:economics / Q000453:epidemiology; D014874:Water Pollutants, Chemical / Q000633:toxicity
D052244:Endocrine Disruptors; D014874:Water Pollutants, Chemical