Sex and adrenal hormone alteration in Ecuadorian adolescents with home and school proximity to floriculture crop area.

Background: Adrenal and sex hormone dysregulation have been independently associated with increased depression and anxiety. Cortisol, an adrenal hormone often used as a marker of stress, can modify the production of sex hormones and may modify the hormone-mood associations. This study evaluated the associations and interplay between sex and adrenal hormones with depression and anxiety among adolescents. Methods: We examined 545 adolescents in rural Pedro Moncayo, Ecuador in 2016 (ages 11-17y, 50.4% female). Depression and anxiety symptoms were assessed using the Children’s Depression Inventory 2nd Edition (CDI-2) and the Multidimensional Anxiety Scale for Children 2nd Edition (MASC-2), respectively. Testosterone, cortisol, dehydroepiandrosterone (DHEA), and estradiol were measured in …

Psychometric properties of the child and adolescent perfectionism scale in ecuadorian adolescents

Background: Pesticides frequently used in agriculture, including organophosphates, glyphosate or 2,4-D, have endocrine disrupting potential. We previously found that residential proximity to agricultural crops (pesticide spray sites) can increase the potential for chronic pesticide exposure of children and adolescents, but little is known about whether residential proximity to crops can affect their hormone levels. Methods: We examined 523 adolescents (12-17 years, ESPINA cohort) living in Pedro Moncayo, Ecuador, where ~21% of the adult population works in floriculture. Using multiple linear regression, we analyzed the association of hormones (DHEA, testosterone, estradiol, and cortisol) with residential proximity to floricultural greenhouses and greenhouse areas near homes. Multiple linear regression models were stratified by whether participants lived closer or farther than 300m from the nearest plantation. Results: We found that 10 percent increases in crop areas within 150m and 200m residential buffer regions were associated with reduced concentrations of testosterone by -0.66 (95%CI: -1.27, -0.06) percent and -0.76 (-1.28, -0.23) precent, respectively. Crop areas within 150m and 500m were also significantly associated with lower estradiol, measured in boys only, by -1.21 (-2.27, -0.14) percent and -0.64 (-1.28, -0.01) percent, respectively. Cortisol was significantly associated with areas within 300m among boys but not girls. Residential proximity to crops within 150m and 200m was inversely associated with testosterone among boys. Conclusions: This is the first study to evaluate geospatial determinants of off-target pesticide drift from crops to nearby homes, including residential proximity to crops and crop surface areas, in relation to hormone alterations. Endocrine disruption of adolescents growing up in agricultural settings is of concern. Keywords: Geospatial, drift, agriculture, pesticides, hormones.

Associations between organophosphate esters and sex hormones among 6–19-year old children and adolescents in NHANES 2013–2014

Testosterone, estradiol, DHEA and cortisol in relation to anxiety and depression scores in adolescents

During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer. METHODS: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25–29 years who participated in the Dietary Intervention Study in Children from 1988–1997 and had sex hormones and sex hormone binding globulin (SHBG) measured in serum collected on 1–4 occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV. RESULTS: Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all Ptrend ≤ 0.03) but not when measured in postmenarche samples (all Ptrend ≥ 0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7% to 22.1% and from 14.1% to 24.3%, respectively. Estrogens, progesterone, androstenedione, and testosterone were not associated with %DBV pre- or post-menarche (all Ptrend ≥ 0.16). CONCLUSIONS: Our results suggest that higher DHEAS and SHBG levels during adolescence, particularly before the onset of menarche, are associated with higher%DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown.

IntroductionDuring adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer.MethodsPercentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25–29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV.ResultsDehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all Ptrend ≤0.03) but not when measured in postmenarche samples (all Ptrend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all Ptrend ≥0.16).ConclusionsOur results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown.Clinical trials registrationClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999

Background:Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents.Methods:We assessed 519 participants (11–17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, , and testosterone was assessed using structural equation modeling.Results:The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0–2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration 95% confidence interval (CI): , ], language [ (95% CI: , )], and memory/learning [ (95% CI: , 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ (95% CI: , )]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed.Conclusion:This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383

BACKGROUND AND AIM: Recent studies suggest that glyphosate has many characteristics of an endocrine disrupting chemical (EDC) through alteration of the hypothalamus-pituitary axis and cellular-signaling, evidenced in in vitro studies of human cell lines and rat models. We assessed the relationship between urinary concentrations of glyphosate with adrenal and gonadal hormones in Ecuadorian adolescents living in an agricultural community. METHODS: We examined 522 adolescents (ages: 11-17y, 50.7% female, 78% Mestizo or White) living in Pedro Moncayo, Ecuador in the summer of 2016 (The ESPINA study), a non-peak pesticide spray season, and measured urinary glyphosate concentration using mass-spectrometry and salivary hormone concentrations using enzymatic methods (dehydroepiandrosterone [DHEA], testosterone, cortisol, and estradiol [the last in boys only]). Saliva was collected upon awakening. Glyphosate was detected in 98% of participants. We conducted pooled and gender stratified multivariate general linear models to assess the relationship between ln-glyphosate and ln-hormone concentrations. Models adjusted for age, race, BMI-for-age z-score, sexual maturation, sample collection time after awakening and ln-creatinine. Estimates were then transformed to present percent difference in hormone concentration per 10% increase in pesticide metabolite concentrations (β). RESULTS:The median glyphosate concentration was 0.87 ng/mL (range: 0.41-1.80 ng/mL, detectable in 98%). In pooled (boys and girls) analyses, a 10% increase in glyphosate concentration was associated with a 0.81% (95% CI: 0.33%, 1.30%) increase in testosterone. This association was stronger in boys (β=1.04% [0.34%, 1.74%]) than girls (β=-0.02% [-0.52%, 0.48%]). Glyphosate was also positively associated with cortisol concentration in boys (β=1.38% [0.45%, 2.32%]) and borderline negatively associated with concentration in girls (β=-0.57% [-1.25%, 0.10%]). No associations were seen for DHEA or estradiol. CONCLUSIONS:Urinary glyphosate was positively associated with concurrent testosterone and cortisol concentrations among male adolescents. Our findings provide some of the first epidemiological data to support prior in-vitro and in-vivo findings that have characterized glyphosate as an EDC. KEYWORDS: Pesticides, Endocrine Disrupting Chemicals, Environmental Epidemiology

Adipose tissue influences steroid conversion by paracrine and autocrine mechanisms. Leptin is secreted by adipocytes and influenced by sex hormones and adiposity. Short-term weight loss in the treatment of childhood obesity reduces leptin and adipose tissue. We therefore asked, Do alterations in sex hormones occur owing to weight loss? and can these alterations be explained by changes in fat mass or sc fat and are alterations in sex hormones directly related to the fall in leptin? Twenty obese boys and 40 obese girls were studied before and after 3 wk of low-calorie diet and physical activity. The weight loss program significantly lowered fat mass, abdominal fat distribution, sc fat (all p < 0.0001), leptin, insulin, and estradiol (all p < 0.0001) but not testosterone. Changes in leptin were related to changes in body mass and to changes in fat mass in boys. In girls, changes in leptin were related to changes in sc fatness and also to changes in insulin. In boys, the reduction in sc fat was positively correlated to changes in testosterone (r = 0.54; p < 0.01) and inversely related to the fall in estradiol (r = -0.41; p < 0.05). In girls, changes in testosterone (r = 0.33; p < 0.05) and in estradiol (r = 0.40; p < 0.01) were related to changes in insulin. Stepwise regression showed that initial leptin was the best determinant for the fall in leptin (adjusted R2 = 0.87; p < 0.0001). The results show that alterations in sex hormones are related to changes in certain fat depots in boys whereas in girls changes in insulin might participate in changes in sex hormones. A greater fall in leptin owing to short-term weight loss is not associated with greater alterations in sex hormones and initial leptin is the best determinant to explain the variability in changes in leptin. The possibility of sex differences in changes in sex hormones secondary to the reduction in fatness warrants further study.

The link between testosterone and amygdala–orbitofrontal cortex connectivity in adolescent alcohol use

Urinary polycyclic aromatic hydrocarbons and sex hormones in children and adolescents: Evidence from NHANES

THE STEROIDAL ACTIONS OF DIGITALIS EDWARD B. Le WINN* William Withering's reintroduction of digitalis to medicine in 1785 marked the first time in the long history of diat drug diat it was shown unequivocally to be of value in the treatment of a specific clinical problem , namely, "die dropsy" [I]. In order to temper the reputation as a treacherous and dangerous medicine which digitalis had acquired through centuries ofabuse, Withering, in the section onEffects, Rules and Cautions of his classic, An Account of the Foxglove, wrote, "Let the medicine [digitalis] . . . be continued until it either acts on Ike kidneys, the stomach, the pulse, or the boweL·; let it be stopped upon thefirst appearance ofany one ofthese effects, and I will maintain diat the patient will not suffer from its exhibition , nor the practitioner be disappointed in any reasonable expectation" (Withering's emphasis). In time diis cautionary note became generally heeded, and it was the accepted practice to prescribe digitalis in courses lasting at most only a week or two at a time. It was not until some 60 years ago that this practice was abandoned in favor of continuous administration over longer periods [2]. It was probably for this reason diat 165 years were to elapse from Withering's account ofthe foxglove to first reports in 1950 [3] and 1953 [4] suggesting that the pharmacodynamics of digitalis include a steroidal action, namely, gynecomastia, elicited clinically during relatively long-term use (months or years), in addition to and in contrast with its long-known cardiotonic effects, which may appear within hours or days. In the 3 decades since the first reports of the steroidal behavior of digitalis [3, 4], sufficient additional information concerning the clinical and laboratory aspects of the effects has been acquired to engage the attention not only of the cardiologist and pharmacologist but of the gynecologist, endocrinologist, urologist, surgeon, oncologist, and Work supported by funds from the Institutes for the Achievement of Human Potential, Philadelphia, Pennsylvania.»Senior attending physician, medicine, emeritus, Albert Einstein Medical Center, Philadelphia, Pennsylvania. Address: Box 439, Upper Black Eddy, Pennsylvania 18972.© 1984 by The University of Chicago. All rights reserved. 0031-5982/84/2702-0380101.00 Perspectives in Biology and Mediane, 27, 2 ¦ Winter 1984 | 183 pathologist as well. A review of the developments on which diis information is based may be ofvalue to these and odier areas ofmedicine. Structural Characteristics ofDigitalis Digitalis, primarily a horticultural term, has in recent years acquired a specific pharmacological meaning, referring to any steroid or steroidglycoside compound that exerts a typical, positive, inotropic, and electrophysiological effect on die heart [5, pp. 945-952]. More than 300 such substances are known to exist in nature, occurring mostly in a wide variety of herbs, flowers, shrubs, and trees but also in the animal kingdom , notably in the skin of the common toad. All digitalis glycosides combine three components: (1) a steroid nucleus to which is attached, at the Cl 7 position, (2) an unsaturated five- or six-member lactone ring, and (3), at the C3 position, a chain of one or more monosaccharide molecules (fig. 1). Chen and Henderson [6] concluded from their study of the pharmacology of 64 cardiac glycosides and aglycones that, although one could not expect complete correlation of structure with biologic behavior , the importance of the spatial arrangements in the molecules ofdiese substances was demonstrated repeatedly. The structural arrangements in some glycosides and aglycones endow them not only with cardiotonic and apparently steroidal but also with convulsive capabilities. It is noteworthy that similar specific relationships exist in the various structural features and the physiological actions of the steroidal hormones , whether those of the glucocorticoids, the mineralocorticQids, or the sex hormones, which have in common with the cardiac glycosides essentially the same steroid nucleus. It is these specific structural relationships that endow each steroidal hormone and each cardiac glycoside with its special biological characteristics. THE STEROID NUCLEUS Through their steroid portion the glycosides are chemically related to cholesterol, bile acids, sterols, and the sex and adrenocortical hormones. The steroid moiety consists of a cyclopentanoperhydrophanthrene nucleus with its C and D rings in the eis or "chair-shaped" configuration. This arrangement is one of the characteristics contributing...

BackgroundBisphenol A (BPA) exposure and its structural analogs (BPS and BPF) might cause endocrine alterations and adverse physiological effects. Few studies to date have directly explored the association between its structural analogs (BPS, BPF) and sex hormones in adult male participants. Therefore, we aimed to assess the associations between BPA, BPS, BPF, and sex hormones in American adult men.MethodsWe used data from the U.S. National Health and Nutrition Examination Survey 2011–2016. We excluded participants without data available on sex hormones and urinary bisphenols. Furthermore, participants consuming sex hormone medications were excluded. Multivariable regression models were performed to assess the association between bisphenols and sex hormones.ResultsIn this study, 2367 participants were included. Of 2367, in 1575 participants, the data on BPS and BPF were available. We found that a per unit increase in BPF was associated with 0.575 ng/dL higher total testosterone (TT) (Model 2: 95% CI: 0.047, 1.103, P = 0.033). However, there was no significant association between BPA or BPS and TT. Furthermore, increased BPA and BPS levels were associated with higher levels of sex hormone-binding globulin (SHBG) (Model 2: β = 0.364, 95% CI: 0.158, 0.571; β = 0.25, 95% CI: 0.071, 0.429, respectively). Additionally, participants in the highest BPA exposure quartile (quartile 4) had 4.072 nmol/L higher levels of SHBG than those in quartile 1 (Model 2: 95% CI: 0.746, 7.397, P = 0.017; P for trend =0.005). Both BPA and BPS were negatively associated with free testosterone (FT, nmol/L) after full adjustment (Model 2, β = − 0.01%, P = 0.0211, P = 0.0211; Model 2, β = − 0.01%, P = 0.0258, respectively). However, BPF was positively associated with FT (Model 2, β = 0.0029%, P = 0.0028).ConclusionOur study indicated that exposure to both BPA and its substitutions could alter sex hormone levels. This finding supports the possibility that human exposure to bisphenols at environmental levels might affect the endogenous hormone balance.

Dementia is a highly prevalent chronic disease among the older population, affecting more than 50 million people worldwide and representing a huge healthcare, social and economic burden. Dementia, and in particular Alzheimer's disease, prevalence is expected to raise within the next few years. Unfortunately, no disease-modifying therapies are available so far, despite a plethora of clinical trials targeting the hallmarks of Alzheimer's disease. Given these premises, it appears crucial to address not only the neuropathological correlates of the disease, but also the modifiable risk factors. Among them, evidence suggest a role of the endocrine system not only in the brain development, but also in the maintenance of its health, having neurotrophic, antioxidant and metabolic functions crucial for the cognitive abilities. This review focuses on the evidence evaluating the impact of the endocrine systems, in particular thyroid function, insulin resistance, parathyroid hormone, vitamin D and sexual hormones on cognitive status. Results from epidemiological, preclinical and some clinical studies demonstrated the link between thyroid, parathyroid hormone and vitamin D and cognitive status, between diabetes, and insulin resistance in particular, and dementia, between sexual and adrenal hormones, particularly estrogen variation at menopause, and cognitive decline. The growing interest on the modifiable risks factors of cognitive decline increased the knowledge about the complex interplay of endocrine systems and cognition, highlighting the need and the usefulness of a multidisciplinary approach to the prevention of a complex and devastating disease.