Exogenous progestogen and estrogen implicated in birth defects.

A five-year study of possible teratogenicity of exogenous female sex hormones included three case-control studies and one cohort study. The first case-control study disclosed an estimated relative risk of 8.41 and a highly significant difference in maternal hormonal exposure (P less than .001) between controls and infants with three major anomalies of the VACTERL group (V, vertebral; A, anal; C, cardiac; T, tracheal; E, esophageal; R, renal; and L,limb). Relative risk (RR) estimates of 5.58 (P = .017) and 3.35 (P less than .001) were found in two case-control studies involving maternal hormonal exposure and patients with congenital heart lesions without other malformations. A controlled, single-blind prospective study disclosed an excess of patients with major malformations (RR = 2.75), congenital heart anomalies (RR = 6), and neurological and neural tube disorders preponderant in the presence of a precipitously declining exposure rate during a three-year period in our referral area.