Mr. Chairman, and Members of the Subcommittees:

I am pleased to appear before you today to present findings concerning the use of diethylstilbestrol (DES) as an "emergency" post coital contraceptive and to provide information on the use of DES as an animal feed additive. I will address the latter use first and point out that the National Cancer Institute remains fully supportive of legislation, regulation and activities which serve to reduce or eliminate environmental exposures to chemical carcinogens. Specifically, if DES were used as an animal feed additive and if residues of the drug were left in edible portions of animals, the result would be long-term exposures to virtually the entire population of the United States. It should be recognized that there is no health advantage to the exposed individual as is the intent when the drug is used therapeutically. The law prescribes

that substances like DES which have been shown to be carcinogenic can be used as feed additives providing no residues appear in any of the edible portions of the animal at the time of slaughter. The NCI

remains fully supportive of these requirements.

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Concern that the newly approved use of DES as a post coital pill

for emergency situations may cause cancer in treated patients is to be viewed in light of present day knowledge and information on human

subjects.

Since the intended use of DES is as a post coital contraceptive for emergency use following unprotected intercourse the primary concern over dangerous side effects, assuming the treatment is effective, would be for the patient. Secondarily, however, concern for the embryo must

be addressed since treatment might be ineffective and a child might be born despite these efforts. First I will speak to the concern for the treated patient.

Among the women treated with DES for threatened abortion no increase in the incidence of cancer at any organ site has been

detected. The dosage of DES and the duration of treatment varied widely from 2.5 150 milligrams per day and from 3 to 212 days. Most of these women were treated with as much as 50 milligrams per day for 150 days or longer. These observations date back to the late 1940's. They show no evidence that such use may be cancer causing. It should be pointed out, however, that such observations

are in contrast to those attendant to the use of DES for treatment of what is

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termed gonadal dysgenesis.

Gonadal dysgenesis in the female

implies defective and incomplete development of the ovaries, and DES has been used in an attempt to correct that condition. Among those patients who have been treated for 5 or more years with an average treatment time of 12 years, evidence exists which suggests an increased risk of an unusual type of cancer. In fact, in a recent study performed by Bruce S. Cutler in 1972, three cases of cancer of this unusual type were discovered among a group of 24 females who had been treated for gonadal dysgenesis over a period of 5 or more years.. Because this form of cancer is so rare, it has been assumed that such treatment puts the patient at increased risk as regards this disease.

The contrast between the cancer experience of women treated for threatened abortion and those treated for defective development of the ovaries can reasonably be assumed to be the result of differences in total dosage and duration of treatment. As indicated earlier, the risk associated with the use of DES as treatment for threatened abortion was so low that it could not be demonstrated.

Only at the higher exposure levels to the drug does evidence exist which suggests an increased cancer risk. On this basis it can

reasonably be assumed that the post coital use which involves 50 milligrams per day for a period of only 5 days would represent far less risk to the patient than did treatment for threatened abortion where indeed no increase in risk could be demonstrated.

Concern for the daughters exposed immediately following conception also needs to be addressed since the effectiveness of treatment is unlikely to be 100%, and the possibility exists that some daughters may be born to treated mothers. Since 1971

there have been extensive studies which document that the

daughters of women treated with DES for threatened abortion during the first 17 weeks of pregnancy have a low but demonstrably increased risk for cancer of the vagina and cervix.

These cancers

appear around the time of puberty but in some cases do not come

Currently,

to clinical attention until several years after puberty. the incidence is estimated to be 3-4 per thousand daughters but this value may increase as the daughters grow older. It should be pointed out, however, that all of these exposures occurred in mothers who were demonstrably pregnant at the time of treatment. This, then, differs markedly from post coital treatment which is