Authors
M. Krstevska-Konstantinova et al., Human Reproduction 16(5):1020-1026, 2001

Sexual precocity after immigration from developing countries to Belgium: evidence of previous exposure to organochlorine pesticides

Numerous reports have been published describing a secular although controversial trend towards earlier onset of puberty. Animal studies have revealed that sexual development can be altered by dietary manipulations as well as treatment with man-made chemicals. However, the association between exposure to environmental chemicals and precocious puberty in the human population remains highly controversial. This study is interesting because the authors describe a retrospective epidemiological study that evaluated a group of 145 patients with precocious puberty (PP) seen in Belgium during a 9-year period. The etiology of PP, country of origin, and data (age, height and BMI) at immigration and diagnosis were evaluated. The authors also examined blood samples from 41 patients to measure pesticides including p,p'-DDE [(1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene)], a main metabolite of the insecticide DDT [1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane].

Among the 145 patients, 28% appeared to be foreign children (39 girls, one boy) originating from numerous developing countries. Both adopted (n=28) and non-adopted (n=12) patients immigrated at similar ages (3.9 and 3.3 years respectively) and were diagnosed with PP at similar ages (7.8 and 8.3 years) after a 4-5 year period of living in Belgium. Based on the live birth rate in Belgium (~100,000 per year) and the number of adopted children reported to the Adoption Registry of Belgium, the prevalence of PP was found to be 80-fold higher in foreign children than in Belgian natives. Since children adopted from developing countries have delayed growth and development due to malnutrition and infectious diseases a delay in puberty onset would have been expected. However, in the present study, the adopted children showed less retarded growth and some patients entered PP. In addition, the present study did not support the idea that a particular ethnic group is at a greater risk of PP due to genetic predisposition. These observations have therefore led to the postulation of the role of environmental agents changing with immigration.

All pesticides were undetectable except for p,p'-DDE. Median serum p,p'-DDE concentrations in foreign adopted (n=15) and foreign non-adopted (n=11) girls with PP were 1.20 and 1.04 ng/ml, respectively. In contrast, the median concentration of p,p'-DDE in the Belgian natives was 0.13 ng/ml. In addition, concentrations of p,p'-DDE were detected in three foreign non-adopted girls with PP that were born in Belgium (data not available). These data suggest a possible intrauterine exposure to pesticides and warrants further study. Organochlorine exposure may be involved in the pathogenesis of PP by stimulating estrogen-sensitive target tissues peripherally and/or centrally. Alternatively, p,p'-DDE acting as an anti-androgen may have displaced testosterone from receptor sites making it available for conversion to estrogens and thus increasing circulating levels of estrogen. Although an interesting study, interpretation of the results is limited due to the small sample size. Further studies should measure p,p'-DDE concentrations in foreign adopted girls showing no PP. These data also suggest that target tissue responsiveness to gonadal steroids may be altered by developmental exposure to environmental agents. This later hypothesis, although interesting, will unfortunately have to be tested in an animal model.