Susceptibility to Creutzfeldt-Jakob disease after human growth hormone treatment in France.

OBJECTIVE:To identify, among the available data concerning host characteristics and exposure, risk factors influencing the susceptibility for developing iatrogenic Creutzfeldt-Jakob disease (iCJD) in a cohort of patients treated with human cadaver-sourced growth hormone (hGH) in France. METHODS:This study included all 1,443 individuals treated in France with hGH from January 1982 to December 1985, out of which 119 cases of hGH-iCJD have been identified so far. We applied a 3 sequential step Cox analysis involving univariable, stepwise, and nonstepwise multivariable procedures. The variables studied were sex, age at hGH treatment initiation, and treatment characteristics (batches and doses). RESULTS:While no effect of age at treatment initiation was observed, a significant effect of sex on disease susceptibility was unexpectedly evidenced with a 2-fold increase of disease occurrence in male patients. This effect did not depend on differences of exposure between male and female patients. We identified 4 categories of hormone batches from high risk to no association with susceptibility. A relationship between the dose received from at-risk hormone batches and the attack rate (number of patients developing the disease among exposed individuals) was demonstrated. CONCLUSIONS:Studying the hGH-exposed patients in France provides epidemiologic evidence of a relationship between dose of inoculum and disease occurrence in humans and suggests an unexpected effect of sex on individual susceptibility.