Association between organochlorine pesticide exposure and thyroid hormones in floriculture workers.

Several studies have suggested that exposure to DDT may be related to changes in thyroid hormone levels in animals and humans, even though results across studies are inconsistent. The aim of this study was to assess the association between exposure to p,p'-DDE (a stable metabolite of DDT) and serum levels of thyroid hormones in floriculture workers. A longitudinal study was conducted on 136 male subjects from the States of Mexico and Morelos, Mexico, who were occupationally exposed to pesticides, during agricultural periods of high (rainy season) and low (dry season) levels of pesticide application. Using a structured questionnaire, a survey was carried out on socio-demographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, residential chemical exposure, and occupational history. Blood and urine samples were collected to determine serum levels of TSH, total T3, total T4, and p,p'-DDE, and metabolites of organophosphate pesticides (OP), respectively. The analysis of the associations between p,p'-DDE levels and thyroid hormone profile adjusting by potential confounding variables including urinary OP metabolites was carried out using multivariate generalized estimating equation (GEE) models. Our results showed that the geometric means of p,p'-DDE levels were 6.17 ng/ml and 4.71 ng/ml in the rainy and dry seasons, respectively. We observed positive associations between the serum levels of p,p'-DDE and those of total T3 (ß=0.01, 95% CI: -0.009, 0.03), and total T4 (ß=0.08, 95% CI:0.03, 0.14) and negative but no significant changes in TSH in male floricultural workers, supporting the hypothesis that acts as thyroid disruptor in humans.

Effect of exposure to p,p'-DDE on male hormone profile in Mexican flower growers.

OBJECTIVES: p,p'-Dichlorodiphenyldichloroethene (p,p'-DDE) acts as an androgen receptor antagonist, however data regarding its hormonal effects in men are limited. The objective of this study was to evaluate the association between serum levels of p,p'-DDE and reproductive hormone profile in Mexican male flower growers. METHODS: A longitudinal study was carried out in a population of men working in the production of flowers and ornamental plants in two Mexican states during July-October 2004 (rainy season) and December 2004-May 2005 (dry season). A questionnaire including information on socioeconomic characteristics, tobacco and alcohol use, presence of chronic and acute diseases, occupational history and anthropometry was used and blood and urine samples were obtained. Serum levels of p,p'-DDE were analysed by gas chromatography; FSH, LH, testosterone, oestradiol, inhibin B and prolactin levels were measured by enzymatic immunoassay. Urinary levels of dialkylphosphates (DAPs) were analysed by gas chromatography. Associations between serum levels of p,p'-DDE and male reproductive hormones (both transformed to their natural logarithm) were evaluated using multivariate generalised estimating equation (GEE) models. RESULTS: Median p,p'-DDE levels were 677.2 ng/g lipid (range 9.4-12 696.5) during the rainy season and 626.7 ng/g lipid (range 9.4-13 668.1) during the dry season. After adjusting for potential confounders (age, body mass index, state of residence and DAPs), p,p'-DDE levels were negatively associated with prolactin (ß=-0.04; 95% CI -0.07 to -0.008) and testosterone (ß=0.04; 95% CI -0.08 to 0.005) and positively with inhibin B (ß=0.11; 95% CI 0.02 to 0.21). CONCLUSION: These results indicate that p,p'-DDE can affect hypothalamic-pituitary-gonadal axis function in humans.

Exposure to organophosphate pesticides and male hormone profile in floriculturist of the state of Morelos, Mexico.

BACKGROUND: Studies on experimental animals have found that organophosphate (OP) pesticides may act as endocrine disruptors; however, their effects on the human hormonal profile have not yet been adequately characterized. We evaluate the association between exposure to OP pesticides, measured through dialkyl phosphate (DAP) metabolites urinary levels, and the male hormone profile. METHODS: A cross-sectional study was performed in 104 floriculturists of Morelos, Mexico. A structured questionnaire was applied to get information on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, and work history. DAP metabolites [dimethylphosphate (DMP), dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate] were determined using gas-liquid chromatography. Serum levels of FSH, LH, prolactin, testosterone, inhibin B and estradiol were determined using enzyme-linked immunosorbent assay. Multiple linear regression was used to study the association between DAP metabolite levels and male hormonal profile. Data were adjusted by p,p'-dichlorodiphenyldichloroethene serum levels and other potential confounders. RESULTS: There was a negative association between inhibin B and urinary levels of DMP, DEP, DETP and total DAP metabolites. DEP levels were negatively associated with serum FSH concentrations, but marginally and positively associated with those of testosterone. DETP was marginally associated with lower LH serum levels. There were no other significant associations among OP metabolites and serum hormone levels. CONCLUSIONS: Inhibin B and FSH vary according to levels of DAP metabolites in men occupationally exposed to OP pesticides. These results suggest that OP pesticides could act as endocrine disruptors in humans; however, most hormonal values fell within the wide normal range and associations were small. There is, therefore, a need for further investigation to elucidate their biological and clinical relevance.

Association between organophosphate pesticides exposure and thyroid hormones in floriculture workers.

The ability of organophosphate pesticides to disturb thyroid gland function has been demonstrated by experimental studies on animal, but evidence of such effects on human remains scarce. The aim of this study was to assess the association between exposure to organophosphate compounds and serum levels of thyroid hormones in floriculture workers. A longitudinal study was conducted on 136 male subjects from the State of Mexico and Morelos, Mexico, occupationally exposed to organophosphate pesticides, during agricultural periods of high (rainy season) and low (dry season) levels of pesticide application. Using a structured questionnaire, a survey was carried out on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, residential chemical exposure, and occupational history. Urine and blood samples were taken the day after pesticide application to determine urine dialkylphosphate (DAP) levels, serum levels of TSH, total T(3), total T(4), serum PON1 activity, and serum p,p'-DEE levels. The analysis of the association between DAP levels and thyroid hormonal profile was carried out using multivariate generalized estimating equation (GEE) models. Our results showed an increase in both TSH and T(4) hormones in serum associated with a increase in total dimethylphosphate levels (SigmaDMP) in urine (p-trend<0.001) and a decrease in total T(3) serum levels with an increase of SigmaDMP levels in the urine (p-trend=0.053). These results suggest that exposure to organophosphate pesticides may be responsible of increasing TSH and T(4) serum hormone levels and decreasing T(3) serum hormone levels, therefore supporting the hypothesis that organophosphate pesticides act as endocrine disruptors in humans.

Interaction between organophosphate pesticide exposure and PON1 activity on thyroid function.

Organophosphate pesticides are widely used in agricultural purposes. Recently, a few studies have demonstrated the ability of these chemicals to alter the function of the thyroid gland in human. Moreover, the paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity. This study evaluates the interaction between exposure to organophosphate compounds and PON1 enzyme activity on serum levels of TSH and thyroid hormones in a population of workers occupationally exposed to pesticides. A longitudinal study was conducted on a population of floriculture workers from Mexico, during two periods of high and low-intensity levels of pesticide application. A structured questionnaire was completed by workers containing questions on sociodemographic characteristics and other variables of interest. Urine and blood samples were taken, and biomarkers of exposure (dialkylphosphates), susceptibility (PON1 polymorphisms and activity) and effect (thyroid hormone levels) were determined. Interaction between dialkylphosphates and PON1 polymorphisms or PON1 activity on hormone levels was evaluated by generalized estimating equation (GEE) models. A significant interaction was found between serum diazoxonase activity and total dialkylphosphates (ΣDAP) on TSH levels. Thus, when PON1 activity was increased we observed a decrease in the percentage of variation of TSH level for each increment in one logarithmic unit of the ΣDAP levels. This interaction was also observed with the PON1(192)RR genotype. These results suggest a stronger association between organophosphate pesticides and thyroid function in individuals with lower PON1 activity.

The impact of a monophasic continuous estro-progestogenic treatment on Latin American menopausal women.

OBJECTIVE: The present study was undertaken to assess the impact, effectiveness and safety of a monophasic hormone replacement treatment (HRT) for continuous use with regards to the clinical effects, bleeding patterns and lipid profile of menopausal women in four Latin American countries. DESIGN: Three hundred and six postmenopausal women with natural menopause and uterus present were recruited. This was a multicentre prospective, clinical trial; the participating countries were Brazil (BR), Colombia (CO), Mexico (MX) and Argentina (AR). The study period was 12 months. The HRT regime was formulated in tablets containing 2 mg estradiol E2 and 1mg norethisterone acetate (NETA); one visit every 3 months was solicited. METHODS: HRT was given as one tablet every day without interruption for 1 year. Climacteric complaints, side-effects, reason for discontinuation, bleeding patterns, lipid profile at baseline and 12 months of treatment were documented. RESULTS: There were no significant differences between the four populations on clinical measurements. Thirty-four women discontinued, 13 for bleeding problems. The five most common side-effects were mastalgia, bleeding problems, headache, pelvic pain and nausea. 44.8% of women experienced scanty vaginal bleeding during the first 3 months of therapy. Ninety seven percent of women had amenorrhea at the end of the study in MX, BR and AR, and 100% in CO. Body weight was constant during the study, and no correlation was found between body weight and total days with bleeding. The Kupperman index score was used to evaluate the climacteric complaints, and the score decreased from a mean of 25.4 to 5.1 at 12-months visit. Total cholesterol levels were significantly reduced in BR and CO (P < 0.05) between baseline and the final sample; serum triglycerides remained unchanged, HDL-cholesterol was significantly increased in MX (P < 0.05), and LDL-cholesterol was significantly reduced in CO (P < 0.05). The results of this 1-year study emphasize that a continuous combined HRT regimen with 2 mg E2/1 mg NETA is an attractive alternative for postmenopausal women who are at least 1 year after their menopause and optimally 2 years after their menopause. Although the combination of 2 mg E2 with 1 mg NETA in a continuous combined therapy scheme has been in use in the Nordic countries for over a decade and in Latin America for the last 6 years, there have been no previous published reports on its effectivity in Latin American women. This publication reports the experience in a group of 306 Latin American women, and it is the first Latin American publication with this formulation.

Symptoms at pre- and postmenopause in rural and urban women from three States of Mexico.

OBJECTIVES: We studied the possible influence of modern cultural conditions on symptoms at menopause in three distant populations, comparing urban vs. rural women from three different States of Mexico: Guanajuato, Coahuila and Yucatán. In these groups we compared the age at menopause and symptoms at pre- and postmenopause. METHODS: A total of 7632 volunteers were selected from Guanajuato, Coahuila and Yucatán. In house visits, an oral questionnaire was applied to women 45-60 years old, non-pregnant or lactating, without hysterectomy, chronic illness, or hormone treatment. We collected general and personal data, clinical, somatometric variables, and symptoms: hot flashes, vaginal dryness, dispareunia, and diminished sexual interest. Depressive mood and anxiety were evaluated with the Hamilton-Bech-Rafaelsen Scale. RESULTS: The mean age at menopause was 48.0 years. A logistic regression identified the association of age at menopause with urban or rural residence, and the State of origin. Scores for depression and anxiety were lower in Yucatán, and they were higher in rural women. Hot flashes, vaginal dryness and the diminished sexual interest were increased at postmenopause. Hot flashes varied from 73 to 32%, and were associated with menopause, low schooling, rural residence, body mass index (BMI), and State of residence. Similar factors were associated with vaginal dryness, dispareunia, and loss of sexual interest. Depressive mood was associated with rural residence, State of residence, menopause, high BMI, smoking habit, age, and schooling. Anxiety was associated with menopause, rural residence, low schooling, high BMI, and age. The loss of sexual interest was associated with age, BMI, menopause and number of pregnancies. CONCLUSIONS: The frequencies of symptoms at menopause have similar ranges to other countries. Ethic and socio-cultural and environmental factors are involved in the appearance or symptoms.

Menstrual pattern and lipid profiles during use of medroxyprogesterone acetate and estradiol cypionate and NET-EN (200 mg) as contraceptive injections.

The objectives of this study were to compare effects of medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg (Cyclofem) and norethisterone enanthate (NET-EN) upon the menstrual pattern and determine changes in lipoprotein parameters after 12 months of use. One-hundred females were included and 87 (45 with Cyclofem and 42 with NET-EN) women completing 12 months were evaluated. Menstrual changes were the leading complaint among users. At the end of 12 months, 20/45 (44.4%) and 18/41 (43.9%) Cyclofem and NET-EN users, respectively, had normal menstrual pattern. Irregular and infrequent bleeding were the two most important changes that occurred. The discontinuation rate at 12 months due to menstrual disturbances did not show any significant differences between the two preparations, but showed lower incidence compared to other studies. Total cholesterol, high-density, low-density and very low-density lipoprotein cholesterol and triglyceride levels decreased at 12 months in both groups and these changes were statistically significant.

A 13-month multicenter clinical experience of a low-dose monophasic oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene in Latin American women.

This prospective, multicenter study was conducted to evaluate the contraceptive reliability, cycle control and tolerability of a 21-day oral contraceptive regimen containing 20 microg ethinylestradiol and 75 microg gestodene in four Latin American countries (Mexico, Argentina, Brazil and Colombia). Participants took trial medication daily for 21 days. Contraceptive efficacy, cycle control and tolerability were evaluated over a period of 13 cycles. Efficacy data gathered from 5,109 treatment cycles were obtained from 393 participants. The trial medication proved to be an effective contraceptive and provided good cycle control. One pregnancy because of poor compliance was recorded. This resulted in a study Pearl index of 0.25. Forty-six percent of Latin American women reported one intracyclic spotting bleeding episode and 37.6% reported one intracyclic breakthrough bleeding (medium/excessive bleeding) episode during cycles 2-4 (primary target). Overall, intracyclic bleeding was reported in 41%. Overall, there was a trend towards a lower incidence of spotting in all the countries and this difference had statistical significance between Argentina and the others three countries (p < 0.05) during cycles 2-4. This trend was also apparent with respect to breakthrough bleeding, but again the difference did not achieve statistical significance. The discontinuation rate because of adverse events was low (3%); no serious adverse events were reported. More than 78% of the women in the four countries maintained constant body weight or lost weight (2 kg) during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study.

Effect of a low-dose contraceptive patch on efficacy, bleeding pattern, and safety: a 1-year, multicenter, open-label, uncontrolled study.

This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high.

Arsenic exposure and calpain-10 polymorphisms impair the function of pancreatic beta-cells in humans: a pilot study of risk factors for T2DM.

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function.