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Marco Procopio, MD, MRCPsych; Paul Marriott, PhD

Arch Gen Psychiatry. 2007;64(12):1402-1407.

Context  Anorexia nervosa (AN) is approximately 10 times more common in females than in males. The reasons for this difference are not yet understood. Several mechanisms have been hypothesized as possible causes.

Objective  To determine whether the different hormonal environments to which male and female fetuses are exposed in utero might contribute to the increased risk of developing AN in females.

Design, Setting, and Participants  The study is based on a large population-based cohort of Swedish twins. The strategy used is to compare the prevalence for AN between same-sex and opposite-sex twins.

Results  The study shows that the risk of developing AN in female twins is higher than in male twins, as expected. The only exception is male members of opposite-sex pairs, who have a higher risk of developing the illness when compared with other males (P  = .62 for narrow diagnostic criteria and P  = .60 for broad diagnostic criteria). In fact, their risk is at a level that is not statistically significantly different from that of females from such a pair. A plausible explanation for this phenomenon is that in pregnancies bearing a female fetus, a substance is produced, probably hormonal, that increases the risk of having AN in adulthood. Because the male half of an opposite-sex twin pair would also be exposed to this substance, it could account for the observed elevated risk in males with female twins. The most likely candidates are sex steroid hormones.

Conclusions  The results of our study are compatible with the hypothesis that intrauterine exposure to sex hormones might influence neurodevelopment, affecting the risk of developing AN in adult life. This might be a factor contributing to the higher risk of developing AN in females.

Author Affiliations: Surrey and Borders Partnership NHS Trust, Chertsey, and Department of Psychiatry, Medical School, University of Sussex, Brighton, England (Dr Procopio); and Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada (Dr Marriott).

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