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Serious psychiatric outcome of subjects prenatally exposed to diethylstilboestrol in the E3N cohort study

Published online by Cambridge University Press:  04 April 2007

HELENE VERDOUX ,
JACQUES ROPERS ,
DOMINIQUE COSTAGLIOLA ,
FRANÇOISE CLAVEL-CHAPELON  and
XAVIER PAOLETTI
HELENE VERDOUX
Affiliation:
INSERM U657; Université Segalen-Bordeaux 2, Bordeaux, France
JACQUES ROPERS
Affiliation:
Agence Française de Sécurité Sanitaire des Produits de Santé, St Denis, France
DOMINIQUE COSTAGLIOLA
Affiliation:
INSERM U720, Paris, France
FRANÇOISE CLAVEL-CHAPELON
Affiliation:
INSERM, Equipe E3N, Villejuif, France
XAVIER PAOLETTI*
Affiliation:
INSERM U738, Paris, France
*
*Address for correspondence: Xavier Paoletti, Institut National du Cancer, Department of Clinical Research and Biostatistics, 52 avenue Morizet, 92513 Boulogne cedex, France. (Email: [email protected])
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Abstract

Background

Prenatal exposure to diethylstilboestrol (DES) may induce neurodevelopmental disturbances potentially mediating an increased risk of psychiatric disorders in exposed subjects. Most findings of an increased prevalence of psychiatric disorders in men and women prenatally exposed to DES are not easy to interpret because of selection biases.

Method

Information on hormonal treatment during pregnancy and on offspring's medical outcome was collected from women participating in the Etude Epidemiologique de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort who completed consecutive postal questionnaires on a range of medical events since 1990. Information on hormonal treatment during pregnancy was collected in 1992 and on offspring's medical outcome in 2004. The psychiatric outcome of subjects prenatally exposed to DES was compared to that of their unexposed siblings.

Results

A total of 1352 mothers with DES treatment for at least one pregnancy provided information on 1680 exposed children and 1447 unexposed siblings. After adjustment for duration of follow-up, educational level, history of obstetric complication, prenatal exposure to progestagen drugs or other hormones and parental history of psychiatric hospitalization, no association was found between prenatal exposure to DES and occurrence of strictly defined serious psychiatric outcome (suicide or psychiatric hospitalization) [adjusted odds ratio (OR) 0·8, 95% confidence interval (CI) 0·5–1·2], or of broadly defined serious psychiatric outcome (same events plus psychiatric or psychological consultation) (adjusted OR 1·0, 95% CI 0·8–1·2).

Conclusions

These findings suggest that the impact of prenatal DES exposure on foetal brain development, if any, is unlikely to increase the risk of serious psychiatric disorders.

Type
Original Article
Information
Psychological Medicine , Volume 37 , Issue 9 , September 2007 , pp. 1315 - 1322
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

Cannon, M., Kendell, R., Susser, E. & Jones, P. (2003). Prenatal and perinatal risk factors for schizophrenia. In The Epidemiology of Schizophrenia (ed. Murray, R., Jones, P., Susser, E., Van Os, J. and Cannon, M.), pp. 74–99. Cambridge University Press: Cambridge.Google Scholar
Clavel-Chapelon, F. (2002). Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women. British Journal of Cancer 86, 723–727.CrossRefGoogle ScholarPubMed
Crow, T. J., Done, D. J. & Sacker, A. (1996). Cerebral lateralization is delayed in children who later develop schizophrenia. Schizophrenia Research 22, 181–185.CrossRefGoogle Scholar
Ehrhardt, A. A., Feldman, J. F., Rosen, L. R., Meyer-Bahlburg, H. F., Gruen, R., Veridiano, N. P., Endicott, J. & Cohen, P. (1987). Psychopathology in prenatally DES-exposed females: current and lifetime adjustment. Psychosomatic Medicine 49, 183–196.CrossRefGoogle ScholarPubMed
Fournier, A., Berrino, F., Riboli, E., Avenel, V. & Clavel-Chapelon, F. (2005). Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. International Journal of Cancer 114, 448–454.CrossRefGoogle Scholar
Fried-Cassorla, M., Scholl, T., Borow, L., Strassman, H. & Bowers, E. (1987). Depression and diethylstilbestrol exposure in women. Journal of Reproductive Medicine 32, 847–850.Google ScholarPubMed
Geschwind, N. & Galaburda, A. (1985). Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and program for research. Archives of Neurology 42, 521–552.CrossRefGoogle Scholar
Gustavson, C. R., Gustavson, J. C., Noller, K. L., O'Brien, P. C., Melton, L. J., Pumariega, A. J., Kaufman, R. H. & Colton, T. (1991). Increased risk of profound weight loss among women exposed to diethylstilbestrol in utero. Behavioral and Neural Biology 55, 307–312.CrossRefGoogle Scholar
Kaufman, R. H., Adam, E., Hatch, E. E., Noller, K., Herbst, A. L., Palmer, J. R. & Hoover, R. N. (2000). Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring. Obstetrics and Gynecology 96, 483–489.Google ScholarPubMed
Lewis, S. & Murray, R. (1987). Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia. Journal of Psychiatry Research 21, 413–421.CrossRefGoogle ScholarPubMed
Meyer-Bahlburg, H. F., Ehrhardt, A. A., Feldman, J. F., Rosen, L. R., Veridiano, N. P. & Zimmerman, I. (1985). Sexual activity level and sexual functioning in women prenatally exposed to diethylstilbestrol. Psychosomatic Medicine 47, 497–511.CrossRefGoogle ScholarPubMed
Murray, R. & Lewis, S. W. (1987). Is schizophrenia a neurodevelopmental disorder? British Medical Journal 295, 681–682.CrossRefGoogle ScholarPubMed
Newbold, R. R. (2004). Lessons learned from perinatal exposure to diethylstilbestrol. Toxicology and Applied Pharmacology 199, 142–150.CrossRefGoogle ScholarPubMed
Orr, K. G., Cannon, M., Gilvarry, C. M., Jones, P. B. & Murray, R. M. (1999). Schizophrenic patients and their first-degree relatives show an excess of mixed-handedness. Schizophrenia Research 39, 167–176.CrossRefGoogle Scholar
Palmlund, I., Apfel, R., Buitendijk, S., Cabau, A. & Forsberg, J. G. (1993). Effects of diethylstilbestrol (DES) medication during pregnancy: report from a symposium at the 10th International Congress of ISPOG. Journal of Psychosomatic Obstetrics and Gynecology 14, 71–89.CrossRefGoogle ScholarPubMed
Pillard, R. C., Rosen, L. R., Meyer-Bahlburg, H., Weinrich, J. D., Feldman, J. F., Gruen, R. & Ehrhardt, A. A. (1993). Psychopathology and social functioning in men prenatally exposed to diethylstilbestrol (DES). Psychosomatic Medicine 55, 485–491.CrossRefGoogle ScholarPubMed
Porrini, S., Belloni, V., Della Seta, D., Farabollini, F., Giannelli, G. & Dessi-Fulgheri, F. (2005). Early exposure to a low dose of bisphenol A affects socio-sexual behavior of juvenile female rats. Brain Research Bulletin 65, 261–266.CrossRefGoogle ScholarPubMed
Reinisch, J. M. & Sanders, S. A. (1992). Effects of prenatal exposure to diethylstilbestrol (DES) on hemispheric laterality and spatial ability in human males. Hormones and Behavior 26, 62–75.CrossRefGoogle Scholar
Romieu, I., Avenel, V., Leynaert, B., Kauffmann, F. & Clavel-Chapelon, F. (2003). Body mass index, change in body silhouette, and risk of asthma in the E3N cohort study. American Journal of Epidemiology 158, 165–174.CrossRefGoogle ScholarPubMed
Schachter, S. (1994). Handedness in women with intrauterine exposure to diethystilbestrol. Neuropsychologia 32, 619–623.CrossRefGoogle Scholar
Scheirs, J. G. & Vingerhoets, A. J. (1995). Handedness and other laterality indices in women prenatally exposed to DES. Journal of Clinical and Experimental Neurophysiology 17, 725–730.Google ScholarPubMed
Slikker, W. Jr., Bailey, J. R., Newport, D., Lipe, G. W. & Hill, D. E. (1982). Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey. Journal of Pharmacology and Experimental Therapeutics 223, 483–489.Google Scholar
Smith, L. L. & Hines, M. (2000). Language lateralization and handedness in women prenatally exposed to diethylstilbestrol (DES). Psychoneuroendocrinology 25, 497–512.CrossRefGoogle ScholarPubMed
Tehard, B., Kaaks, R. & Clavel-Chapelon, F. (2005). Body silhouette, menstrual function at adolescence and breast cancer risk in the E3N cohort study. British Journal of Cancer 92, 2042–2048.CrossRefGoogle Scholar
Titus-Ernstoff, L., Perez, K., Hatch, E. E., Troisi, R., Palmer, J. R., Hartge, P., Hyer, M., Kaufman, R., Adam, E., Strohsnitter, W., Noller, K., Pickett, K. E. & Hoover, R. (2003). Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol. Epidemiology 14, 155–160.CrossRefGoogle ScholarPubMed
Verdoux, H. (2002). Long-term psychiatric and behavioural consequences of prenatal exposure to psychoactive drugs [in French]. Therapie 57, 181–185.Google ScholarPubMed
Verdoux, H. (2004). Perinatal risk factors for schizophrenia: how specific are they? Current Psychiatry Reports 6, 162–167.CrossRefGoogle Scholar
Verdoux, H., Geddes, J., Takei, N., Lawrie, S., Bovet, P., Eagles, J., Heun, R., McCreadie, R., McNeil, T., O'Callaghan, E., Stöber, G., Willinger, U., Wright, P. & Murray, R. (1997). Obstetric complications and age at onset in schizophrenia. An international collaborative meta-analysis of individual patient data. American Journal of Psychiatry 154, 1220–1227.Google ScholarPubMed
Vessey, M. P., Fairweather, D. V., Norman-Smith, B. & Buckley, J. (1983). A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring. British Journal of Obstetrics and Gynaecology 90, 1007–1017.CrossRefGoogle ScholarPubMed
Watier, L., Richardson, S. & Hemon, D. (1997). Accounting for pregnancy dependence in epidemiologic studies of reproductive outcomes. Epidemiology 8, 629–636.CrossRefGoogle ScholarPubMed