Hormone therapy during pregnancy and isolated hypospadias: an international case-control study

Mothers of boys with hypospadias and control mothers were interviewed in eight malformation monitoring programs around the world. Hormone therapy was used quite frequently in five but rarely in three of the programs. The odds ratio for hypospadias after hormone therapy during pregnancy was 2.8 (95% confidence limits 1.2, 6.9) but there was no correlation between the timing of hormone therapy and the location of the urethral orifice, nor between the severity of the malformation and hormone therapy. Programs with the highest hormone exposure rate showed the lowest odds ratio for pregnancy bleeding, the most common reason for hormone therapy. These latter findings cast doubts on the causal association between hormone therapy and isolated hypospadias. Alternative explanations are recall or interviewer bias or unidentified confounders.