Human exposure to endocrine disrupting chemicals and fertility: A case–control study in male subfertility patients

Highlights

• Exposure to endocrine disruptors was studied in male subfertility patients.

• Chlorinated pesticides in serum were associated with increased risk of subfertility.

• Brominated flame retardants negatively influence fertility in men.

• Phthalates, triclosan and bisphenol A affect sex hormone levels.

Abstract

Background

Dioxins, PCBs, chlorinated pesticides, brominated flame retardants, bisphenol A, triclosan, perfluorinated compounds and phthalates are known as endocrine disrupting chemicals (EDCs).

Objectives

The aim of our study was to investigate whether higher exposure to EDCs is associated with increased subfertility in men.

Methods

We measured biomarkers of exposure in 163 men, recruited through four fertility clinics. According to WHO guidelines, we used a total motility count (TMC) of 20 million as cut-off value. We assigned patients to the case group when two semen samples – collected at least one week apart – had a TMC < 20 and to the control group when both samples had a TMC ≥ 20. To estimate the risk of subfertility and alteration in sex hormone concentrations we used multivariable-adjusted analysis, using logistic and linear regressions, respectively.

Results

For an IQR increase in serum oxychlordane, the odds ratio for subfertility was 1.98 (95% CI: 1.07; 3.69). Furthermore, men with serum levels of BDE209 above the quantification limit had an odds of 7.22 (1.03; 50.6) for subfertility compared with those having values below the LOQ. Urinary levels of phthalates and triclosan were negatively associated with inhibin B and positively with LH. Urinary bisphenol A correlated negatively with testosterone levels.

Conclusions

Our study in men showed that internal body concentrations of endocrine disrupting chemicals are associated with an increased risk of subfertility together with alterations in hormone levels. The results emphasize the importance to reduce chemicals in the environment in order to safeguard male fertility.

Introduction

In 1985, Hull et al. (1985) assessed subfertility in 708 couples in a single health district in England and concluded that at least one in six couples need specialist help at some point in their lives because of subfertility. In a recent U.S. study, the estimated prevalence of infertility was 12.0% (95% CI: 7.0; 23.2) (Louis et al., 2013). It is generally assumed that the low fertility rates in the industrialized countries are the result of social and economic changes, such as women's careers, postponed child wish, declining ideal family size, instability of partnership, etc. However, there is growing evidence to suspect that lifestyle factors and increasing environmental exposure to endocrine disrupting chemicals (EDCs) are also contributing to the trends in occurrence of reproductive health problems. Prenatal exposure to EDCs may be associated with anomalies of the testicular dysgenesis syndrome (TDS) later in life, which includes reduced semen quality, increased incidence of cryptorchidism and hypospadias, and increased incidence of testis cancer (Sharpe and Skakkebaek, 1993). These reproductive-tract abnormalities can be brought about by estrogen-induced changes during fetal development, i.e. by reducing Sertoli cell numbers and impairing Leydig cell development (Sharpe and Skakkebaek, 1993).

Although fertility is a condition of a couple, where the reproductive health of both sexes plays a role, there is accumulating evidence that semen quality in humans is decreasing over time (Carlsen et al., 1992, Le et al., 2014) and may play a role in the impaired reproductive outcomes. Decreased fertility rates due to environmental exposure to EDCs have important financial implications for the society. Recently, an international expert panel estimated the economic costs for male infertility attributable to phthalate exposure in Europe, with a 40–69% probability of causing 618 000 additional assisted reproductive technology procedures, at €4.71 billion annually (Hauser et al., 2015).

Subfertility in this study was defined as ‘involuntary infertility’, indicating that a couple has unsuccessfully tried to obtain pregnancy during 12 months or more (Slama et al., 2014).

The use of biomarkers can help to identify possible links between subfertility and exposure to EDCs at the individual level. In this case–control study in male subfertility patients, we assessed exposure to environmental contaminants from historical sources, such as dioxins, PCBs and chlorinated pesticides, as well as emerging chemicals such as phthalates, bisphenol A (BPA), triclosan, brominated or perfluorinated compounds that are present in a growing number of daily consumption products, such as personal care products, clothing, carpeting, packaging, cooking materials, electronic and electrical equipment, etc. These chemicals are all known to have hormone disrupting properties. PCBs have both estrogenic and anti-estrogenic effects depending on the congener, while dioxins are well-known anti-estrogens (Bonefeld-Jorgensen et al., 2014); phthalates may act as anti-androgens (Latini et al., 2004); BPA has been shown to exhibit estrogenic activity (Maffini et al., 2006); reproductive effects from perfluorinated compounds have been observed in experimental animals as well as changed hormone levels (Bonefeld-Jorgensen et al., 2014, Taxvig et al., 2014). In observational human studies, effects on sperm quality were reported for chlorinated persistent compounds (Toft, 2014), phthalates (Kay et al., 2014) and perfluorinated compounds (Toft et al., 2012).

The aim of our study was to investigate whether higher exposure to EDCs is associated with increased subfertility in men, defined on the basis of semen parameters. In order to understand underlying mechanisms, serum sex hormone concentration levels were measured and studied in relation to the biomarkers of exposure.