Thyroid and reproductive hormones in relation to pesticide use in an agricultural population in Southern Brazil
Introduction
Many contemporary pesticides are suspected of disrupting the endocrine function by blocking or activating hormone receptors and/or to affect hormone levels (Campos and Freire, 2016; McKinlay et al., 2008; Mnif et al., 2011). In vitro studies suggest that a variety of non-persistent currently used pesticides, including organophosphates (OP), carbamates, and synthetic pyrethroids, and several herbicides and fungicides may exert estrogenic and/or anti-androgenic activity and disturb sex steroid-synthesizing enzymes like cytochrome (CYP) 19 (aromatase) and CYP17 (Andersen et al., 2002; Kojima et al., 2004; Orton et al., 2011; Saillenfait et al., 2016). Likewise, animal studies suggest that exposure to numerous modern pesticides may alter thyroid function (Campos and Freire, 2016; McKinlay et al., 2008).
Given the ability of many modern pesticides to disrupt the endocrine system, several human studies suggest associations between pesticide exposure and adverse endocrine or reproductive outcomes, including declined sperm quality (Cremonese et al., 2017; Perry, 2008), adverse pregnancy outcomes (De Araújo et al., 2016, 2017; Parvez et al., 2018), altered puberty timing (Ye et al., 2017a,b), and increased risk of hormone-dependent cancers (Engel et al., 2017; Lerro et al., 2015) and clinical thyroid disease (Goldner et al., 2010, 2013; Lerro et al., 2018; Shrestha et al., 2018a,b). Accordingly, a growing number of epidemiological studies have reported links between exposure to several contemporary pesticides and subtle alterations in circulating levels of reproductive or thyroid hormones in both adults from the general population (Fortenberry et al., 2012; Han et al., 2008; Jain, 2016, 2017; Meeker et al., 2006, 2008, 2009) and male agricultural workers (Aguilar-Garduño et al., 2013; Khan et al., 2013; Lacasaña et al., 2010; Lerro et al., 2018; Panganiban et al., 2004; Recio et al., 2005; Steenland et al., 1997). However, findings from these studies are inconsistent, with null, inverse, as well as positive associations between exposures and hormone levels, mostly with regard to sex hormones. Other studies explored seasonal variation or short-term changes in thyroid or reproductive hormone levels in relation to professional pesticide use also showing inconclusive results (Garry et al., 2001, 2003; Lacasaña et al., 2010; Larsen et al., 1999; Straube et al., 1999; Toft et al., 2006). Overall, current knowledge regarding the impact of contemporary-use non-persistent pesticides on hormone levels is still limited and its clinical implications remain unclear.
Brazil became in 2008 the largest consumer of agricultural pesticides in the world, and continues to use a range of pesticides banned in most other countries. Serra Gaúcha, in the State of Rio Grande do Sul, South of Brazil, is a predominantly rural region characterized by family farms mostly dedicated to fruit production, especially wine grape growing. In a previous cross-sectional study on male and female farm residents in Serra Gaúcha, we found that total lifetime use of herbicides and dithiocarbamate fungicides was associated with increased thyroid-stimulating hormone (TSH) and decreased free thyroxine (T4) among men (Piccoli et al., 2016). In addition, men sampled in the season of high pesticide use showed higher TSH levels when compared to those sampled in the season of low pesticide use. Conversely, farm work and lifetime use of pesticides were related with a slight decrease in TSH and increases in total triiodothyronine (T3) and free T4 values. In a subsequent study among rural and urban young men from the same population, lifetime use of herbicides and fungicides was associated with poorer sperm morphology and low luteinizing hormone (LH) and prolactin levels (Cremonese et al., 2017). With the above background, the current study aimed to determine whether recent pesticide exposure in agricultural population of this region causes disturbance of thyroid and reproductive serum hormone levels. To do this, serum samples from agricultural workers and farm family members were sampled both in the low and high pesticide use season under the hypothesis that seasonal differences in pesticide use results in altered individual hormone levels, assuming transitory effects. On the other hand, because long-term exposure to pesticides may produce sustained effects, the association between cumulative lifetime exposure to agricultural pesticides and changes in serum hormone levels was also examined.
Section snippets
Population and study design
The study participants were drawn from the sample of farm residents that participated in our previous survey in Serra Gaúcha region (Cremonese et al., 2017; Piccoli et al., 2016). Of the 275 subjects included in the survey, 50 men with at least one year of agricultural work experience were randomly selected and informed about the current research. We invited these 50 men and family members aged 18 years or older and residing on the farm house. A total of 132 subjects were invited, of which 122
Results
Table 1 summarizes characteristics of the study population, composed of 75 men and 47 women. Mean age of participants was 46 years (range: 18–70), 58% had <9 years of schooling, 7% were current smokers, up to 70% reported frequent alcohol intake in the last month, 64% did not practiced any physical activity over the last year, and 59% were overweight or obese. Eleven subjects had ever been diagnosed with hypothyroidism, one with hyperthyroidism, and 4 had a history of thyroid nodules.
There were
Discussion
In this study of farm residents, we observed significantly lower serum levels of total T4 and male testosterone in the heavy pesticide use season compared to the low pesticide use season. Moreover, in the harvesting season we found associations 1) of recent use of dithiocarbamate fungicides, not using full PPE, and use of manual equipment in the last pesticide application with reduced TSH; 2) of recent use of the pyrethroid lambda-cyhalothrin and the herbicide paraquat with reduced total T4 and
Conclusions
In summary, our study suggests that short-term exposure to agricultural pesticides could lead to decreased serum levels of total T4, TSH, and male testosterone, and may provide evidence for the endocrine disruptive potential of specific pesticides, including lambda-cyhalothrin, phthalamide, and paraquat. In addition, reduction of total T4 with unchanged TSH levels and increase in male testosterone appeared to be the most significant effect of long-term pesticide exposure. As several pesticides
Acknowledgments
The authors are grateful to the study participants, the “Prefeitura Municipal de Farroupilha-RS”, the “Centro Universitário da Serra Gaúcha-FSG”, and the “Pró Análisis” Laboratory. The authors are also grateful to the Carlos III Institute of Health (ISCIII) for the research contract granted to C. Freire (Miguel Servet-FEDER fund MS16/00085).
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