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Rogelio Recio,^1,2 Guadalupe Ocampo-Gómez,² Javier Morán-Martínez,² Victor Borja-Aburto,³ Malaquías López-Cervantes,⁴ Marisela Uribe,¹ Luisa Torres-Sánchez,⁴ and Mariano E. Cebrián¹

¹Sección Externa de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México; ²Departamento de Salud Ambiental, Centro de Investigación Biomédica, Facultad de Medicina de Torreón, Universidad Autónoma de Coahuila, Torreón, Coahuila, México; ³Instituto Mexicano del Seguro Social, México DF, México; ⁴Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.

Abstract
Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas-liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP ; 55%) , followed by diethylphosphate (DEP ; 46%) , dimethylthiophosphate (DMTP ; 32%) , and dimethyldithiophosphate (DMDTP ; 31%) . However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%) . The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamic-pituitary endocrine function and also indicates that FSH and LH are the hormones most affected. Key words: alkylphosphates, endocrine disruptors, estradiol, FSH, LH, organophosphorous pesticides, prolactin, testosterone. Environ Health Perspect 113:1160-1163 (2005) . doi:10.1289/ehp.7374 available via http://dx.doi.org/ [Online 10 May 2005]

Address correspondence to M.E. Cebrián, Sección de Toxicología, CINVESTAV, P.O. Box 14-740 Avenida Instituto Politécnico Nacional No. 2508, Col. Zacatenco, Delegación Gustavo A. Madero, CP 07300, México DF, México. Telephone: 52-5-5061-3309. Fax: 52-5-5061-3395. E-mail: mcebrian@mail.cinvestav.mx

We thank C. Hernández, P. Nava, and R.M. García for chemical analysis and A. Gómez-Muñoz for statistical advice.

This study was partially supported by grants from the Consejo Nacional de Ciencia y Tecnología (CONACYT ; 28403-M) , the World Health Organization Human Reproduction Program (96349) , University of California Institute for Mexico and the United States (UC-MEXUS) , and the National Institutes of Health/Fogarty International Center Training and Research in Environmental and Occupational Health (TW00623) .

The authors declare they have no competing financial interests.

Received 30 June 2004 ; accepted 10 May 2005.

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