Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union

Russ Hauser; Niels E Skakkebaek; Ulla Hass; Jorma Toppari; Anders Juul; Anna Maria Andersson; Andreas Kortenkamp; Jerrold J Heindel; Leonardo Trasande

doi:10.1210/jc.2014-4325

Lifestyle and Environment · Environmental Exposures

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union

Hauser R, Skakkebaek NE, Hass U, Toppari J, Juul A, Andersson AM, Kortenkamp A, Heindel JJ, Trasande L

Published April 2015 The Journal of clinical endocrinology and metabolism

DOI 10.1210/jc.2014-4325 PMID 25742517 PMC PMC4399287

RRM Academy Synopsis

Phthalates may contribute to male infertility and costs in the EU

In a cost model for the European Union in 2010, an expert panel gave phthalates a 40 to 69% probability of causing male infertility. At that probability, the model counts 618,000 additional ART procedures, costing €4.71 billion annually. It also priced undescended testicles, testicular cancer and low testosterone.

Key Findings

For phthalates and male infertility, the panel found low epidemiological and strong toxicological evidence and a 40 to 69% probability of causation, with an attributable increment in infertility of 9.38%.
From that increment, the model estimates 618,000 additional ART procedures costing €4.71 billion, assuming 56% of couples with a time to pregnancy over 12 months proceed to ART.
Prenatal exposure to polybrominated diphenyl ether (PBDE) flame retardants carried a 40 to 69% probability of causing undescended testicles, with low epidemiological and strong toxicological evidence and 4615 cases costing €130 million.
PBDEs and testicular cancer drew a 0 to 19% probability of causation, with very low epidemiological and weak toxicological evidence and 6830 potential cases a year at €848 million.
The panel gave phthalates a 40 to 69% probability of lowering testosterone in men aged 55 to 64, linked to 24,820 deaths a year and €7.96 billion in lost economic productivity.

Interpretation

The study is a model of disease burden and cost, built by an expert panel from published studies. The panel scored each chemical and outcome pair on a scale from the Intergovernmental Panel on Climate Change. The scale states cause as a probability range. The infertility estimate draws on a longitudinal study of 505 couples planning a pregnancy. The undescended testicle and testicular cancer estimates each draw on one case-control study. The authors say they modeled only chemicals with enough studies and left out combined exposure to several chemicals.

RRM Context

Restorative reproductive medicine looks for root causes in both partners. Male reproductive health belongs in the first evaluation. Environmental exposure is one root-cause question for poor semen quality or low testosterone. The paper prices phthalate-attributable male infertility by the cost of ART procedures. ART goes around the problem without finding why conception fails.

Our editorial summary of this paper, not the article's abstract.

Abstract

Introduction

Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders.

Purpose

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.

Topics

Lifestyle and Environment › Environmental Exposures › Endocrine Disrupting Chemicals · Male Fertility › Male Factor Causes › Lifestyle and Environment · Cost and Access › Cost of Care › Treatment Costs

Russ Hauser, Niels E Skakkebaek, Ulla Hass, Jorma Toppari, Anders Juul, Anna Maria Andersson, Andreas Kortenkamp, Jerrold J Heindel, Leonardo Trasande

R Hauser, N Skakkebaek, U Hass, J Toppari, A Juul, A Andersson, A Kortenkamp, J Heindel, L Trasande

PMID 25742517 25742517 DOI 10.1210/jc.2014-4325 10.1210/jc.2014-4325 Hauser et al. 2015, Hauser 2015

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union

Phthalates may contribute to male infertility and costs in the EU

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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