There is growing evidence that organophosphate, pyrethroid, and neonicotinoid pesticides may be endocrine-disrupting chemicals (EDCs). Endocrine alterations by these three classes of insecticides have been observed in experimental studies of rats (Alaa-Eldin et al., 2017a; Hu et al., 2013; Bal et al., 2012; Tetsatsi et al., 2019), mice (Wang et al., 2019; Bhaskar et al., 2017), and fish (Tian et al., 2017; Crago and Schlenk, 2015; Ghasemzadeh et al., 2015). The limited epidemiological evidence of hormone disruption due to insecticide exposure has mostly been in adult populations and are focused on gonadal hormone outcomes, such as alterations in testosterone, estradiol, and dehydroepiandrosterone (DHEA) concentrations (Suárez et al., 2021; Mendy and Pinney, 2022; Suwannarin et al., 2021; Meeker et al., 2009a). Endocrine disruption can negatively affect human health, as it has been linked to health conditions including, but not limited to, depression and anxiety symptoms (Chronister et al., 2021), cancer, diabetes, and reproductive and developmental alterations (Kabir et al., 2015).

In epidemiologic studies, organophosphate exposure has also been linked to reduced concentrations of testosterone, total testosterone, free testosterone, and testosterone to estradiol ratios in adult males (Aguilar-Garduño et al., 2013; Dziewirska et al., 2018; Gravel et al., 2020; Omoike et al., 2015; Qin et al., 2020). In a cohort of men who were patients of the Massachusetts infertility clinic, there was a dose-dependent increase in the odds of being in the lowest estradiol quintile with increasing exposure to 3,5,6-Trichloro-2-pyridinol (TCPy) (Meeker et al., 2008). In a study of 116 Spanish male adolescents, non-occupational exposure to TCPy was also inversely associated with estradiol and follicle stimulating hormone (FSH) and positively associated with DHEA sulfate (DHEAS), while exposure to 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy) was directly associated with estradiol, DHEAS, and FSH (Suárez et al., 2021). Organophosphate pesticides are known to inhibit the enzymatic activity of acetylcholinesterase (AChE). The central cholinergic system has been shown to modulate the hypothalamic-pituitary-adrenal axis in rats, which controls adrenal hormone secretion (Rhodes et al., 2002). To our knowledge, no studies have directly assessed the effects of AChE disruption on testosterone, estradiol, DHEA, and cortisol hormones.

Research on the effects of neonicotinoid insecticides on endocrine alterations is limited. Using data from the 2015–2016 National Health and Nutrition Examination Study (NHANES) examination, in men, women, and children both n-desmethyl-acetamiprid and 5-hydroxy-imidacloprid (OHIM) were associated with decreased free androgen index which estimates physiologically active testosterone (Mendy and Pinney, 2022). OHIM was also associated with decreased serum total testosterone in women (Mendy and Pinney, 2022). In male farmworkers in Northern Thailand, imidacloprid exposure was associated with increased testosterone, dehydrocorticosterone, and DHEA (Suwannarin et al., 2021). N-desmethyl-acetamiprid exposure was associated with increased androstenedione, an endogenous weak androgen steroid hormone helping in the biosynthesis of estrone and testosterone from dehydroepiandrosterone (Suwannarin et al., 2021).

Exposures to pyrethroids have also been associated with endocrine alterations (Alaa-Eldin et al., 2017a; Hu et al., 2013; Wang et al., 2019; Crago and Schlenk, 2015). Pyrethroids have been found to induce significant estrogenicity in Var-I human endometrial cancer cell line (Suárez et al., 2021) and MCF-7 human breast carcinoma cell line (Go et al., 1999), and antagonize progesterone action in T47D human cell lines (Garey and Wolff, 1998). While in a study of adult men recruited from an infertility clinic observed that the urinary metabolites 3-phenoxybenzoic acid (3-PBA), cis- (cis-DCCA) and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA) were positively associated with FSH and luteinizing hormones (LH) (Meeker et al., 2009b). In men, LH stimulates testosterone production from Leydig cells, while FSH stimulates spermatogenesis and Sertoli cell function (Dandona and Rosenberg, 2010). Trans-DCCA was also inversely associated with testosterone and free androgen index (Meeker et al., 2009b).

Adolescents living in agricultural communities have increased risk of exposure to pesticides, through pesticide drift from spray sites to nearby homes, direct contact with fumigated crops, parental take-home pathways, and behavioral activities (Simcox et al., 1995; Garry, 2004). Children and adolescents are at higher risk, as they are more susceptible to the effects of toxic exposures (Landrigan and Goldman, 2011) and endocrine disruption at this stage can have life-long effects (Kabir et al., 2015). Thus, it is imperative to identify whether organophosphate, neonicotinoids and pyrethroids contribute to endocrine disruption in adolescent populations. Considering the potential for hormone imbalances associated with pesticide exposures among adolescents, and the dearth of studies in this age-group, this study aimed evaluate whether biomarkers of exposures to organophosphate, neonicotinoids, and pyrethroid insecticides were associated with alterations in sex and adrenal hormones in Ecuadorian adolescents living in agricultural communities.