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Mariana F. Fernandez,¹ Begoña Olmos,¹ Alicia Granada,¹ Maria José López-Espinosa,¹ José-Manuel Molina-Molina,¹ Juan Manuel Fernandez,² Milagros Cruz,³ Fátima Olea-Serrano,⁴ and Nicolás Olea¹

¹Laboratory of Medical Investigations, ²Department of Pediatrics, and ³Department of Gynecology and Obstetrics, San Cecilio University Hospital, Granada, Spain; ⁴Department of Nutrition, University of Granada, Granada, Spain

Abstract
Background: Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs.

Objective: In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations.

Methods: In a case–control study, nested in a mother–child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) .

Results: TEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus nondetectable TEXB of 2.82 (95% CI, 1.10–7.24) . More pesticides were detected in cases than in controls (9.34 ± 3.19 vs. 6.97 ± 3.93) . ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p´-DDT (OR = 2.25 ; 95% CI, 1.03–4.89) , p,p´-DDT (OR = 2.63 ; 95% CI, 1.21–5.72) , lindane (OR = 3.38 ; 95% CI, 1.36–8.38) , mirex (OR = 2.85 ; 95% CI, 1.22–6.66) , and endosulfan alpha (OR = 2.19 ; 95% CI, 0.99–4.82) . Engagement of mothers in agriculture (OR = 3.47 ; 95% CI, 1.33–9.03) , fathers' occupational exposure to xenoestrogens (OR = 2.98 ; 95% CI, 1.11–8.01) , and history of previous stillbirths (OR = 4.20 ; 95% CI, 1.11–16.66) were also associated with risk of malformations.

Conclusions: We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta.

Key words: cryptorchidism, endocrine-disrupting chemicals, environmental estrogens, hypospadias, occupational exposure, risk factors. Environ Health Perspect 115(suppl 1) :8–14 (2007) . doi: 10.1289/ehp.9351 available via http://dx.doi.org/ doi:10.1289/ehp.9351 available via http://dx.doi.org/ [Online 8 June 2007]

This article is part of the monograph "Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects."

Address correspondence to M.F. Fernandez at the Laboratory of Medical Investigations, San Cecilio University Hospital, 18071-Granada, Spain. Telephone: 34-958-242864. Fax: 34-958-249953. E-mail: marieta@ugr.es

M.F.F. and B.O. contributed equally to this article.

We are indebted to all participants, without whom this work would not have been possible. We are grateful to the nursing staff for their cooperation, K. Main for her critical reading of this manuscript, and R. Davies for editorial assistance.

The study was supported by "INMA Study" G03/176 (Ministry of Health) , SAS 202/04 (Andalusia Government) , and QLK4-1999-01422 and QLK4-2002-00603 (European Commission) .

The authors declare they have no competing financial interests.

Received 22 May 2006 ; accepted 30 October 2006.