PROGESTATIONAL DRUG BIRTH DEFECTS WARNING STATEMENT

PROGESTATIONAL DRUG BIRTH DEFECTS WARNING STATEMENT should be deleted from current class progestrone labeling, FDA's Fertility and Maternal Health Drugs Advisory Committee recommended at its Jan. 8 meeting. Committee chairperson Carolyn Coulam, MD, Methodist Hospital of Indiana, said, "It was the unanimous consensus of the committee that this warning label should be deleted from the labeling from all progestational agents." The specific progestational agents under consideration were progesterone, 17 alpha hydroxyprogesterone caproate and medroxyprogesterone. The warning label, which has been required since 1977, states: "Several reports suggest an association between the intrauterine exposure to female sex hormones and congenital anomalies including congential heart defects and limb reduction defects." The committee recommended that the warning be deleted because the association between birth defects and progesterone exposure is not statistically significant in the studies reported. "Our charge here today is to make sure that those warnings do contain accurate information," Coulam said. The warning may cause unwarranted concern, the committee said. "The implications that progestational agents are proved carcinogens . . . provokes panic and possibly unnecessary abortions by anxious women," committee consultant Joe Simpson, MD, American College of Obstetricians and Gynecologists, declared. FDA staffer Ridgely Bennett, MD, in his presentation, cited a 1985 study by Katz, et al, which failed to find an association between congenital anomalies and the exposure to medroxyprogesterone acetate. The objective was to detect possible teratogenic effects of medroxyprogesterone and 17 alpha hydroxyprogesterone caproate given during early pregnancy in a controlled non-concurrent, prospective study of 2,754 infants born to mothers who had bled during the first trimester of pregnancy. Of the study group, 1,600 were infants of mothers treated with progesterones, including 1,274 mothers who received oral medroxyprogesterone acetate exclusively, and 334 who received 17 alpha hydroxyprogesterone caproate alone or in combination with medroxyprogesterone. The control group consisted of 1,146 infants of untreated mothers. All the infants were examined and no significant difference was found between the treated and the control groups with respect to malformations. Two other warning statements were under consideration for addition to the boxed warning for progestational agents. One proposed statement suggested an association between intrauterine exposure to the agents and "masculinization of the external genitalia of the female fetus." The second proposed statement suggested a link between exposure and "hypospadias of the male fetus." The committee decided to defer a recommendation on the genital tract issue until a subcommittee can review available data and make a report to the full committee. Franz Rosa, MD, FDA, cited a survey that showed 1.265 mil. progesterone Rxs were written between 11/85 and 10/86 to women 20-39 years old. Valid indications for progestrone treatment include premenstrual syndrome and threatened abortion, Rosa said.