The Food and Drug Administration ruled yesterday that the millions of middle-aged women who take drugs containing estrogen for a year or longer must be warned repeatedly that they are multiplying the normal risk of cancer of the uterus five to 10 times.
Starting Sept. 21, the FDA will require pharmacists and physicians who dispense estrogen - the female sex hormone - to provide users with a special plain-language brochure each time they fill a prescription.
The brochure rejects promotional claims, which manufacturers and others have made for more than a decade, that prolonged use of estrogen actually may prevent cancer and, in the process, keep users "feminine forever."
"You may have heard that taking estrogens for long periods (years) after the menopause will keep your skin soft and supple and keep you feeling young," the brochure says at one point. "There is no evidence that this is so, however, and such long-term treatment carries important risks."
Manufacturers will print the brochures, Ayerst Laboratories, a division of American Home Products Corp., makes the most widely prescribed brand, Premarin.
Currently, the FDA estimates, 3 million women take the drugs for both menopausal and post-menopausal symptoms. About twice as many were taking them in December, 1975, when three separate teams of scientists reported that long-term estrogen intake increases the risk of cancer of the endometrium (lining of the uterus).
FDA Commissioner Donald Kennedy said the agency is "concerned that estrogens are used too frequently and for too long, and our aim is that the information to be provided to patients will lead to better use of these drugs - including less pressure on physicians to prescribe them."
Last year the FDA tightened the estrogen prescribing instructions for physicians. Only once before, however, has the agency required that crucial facts about a prescription drug be provided directly to consumers.
The brochure, which will be published Friday in the Federal Register, says that estrogens have "important uses," but makes these key points:
". . . considerably more than half of all women undergoing the menopause have only mild symptoms or no symptons at all and therefore do not need estrogens. Other women may need estrogens for a few months," while they adjust to the lower estrogen levels naturally occurring in the body usually between ages 45 and 55.
"Sometimes women experience nervous symptons or depression during menopause. There is no evidence that estrogens are effective for such symptoms and they should not be used to treat them . . ."
Because a postmenopausal estrogen user has five to 10 chances per 1,000 each year of getting endometrial cancer, compared with a nonuser's one per 1,000, "it is important to take estrogens only when you really need them."
"The risk of this cancer is greater the longer estrogens are used and also seems to be greater when larger doses are taken. For this reason, it is important to take the lowest dose of estrogen that will control symptoms and to take it only as long as it is needed."
In animals, estrogens can cuase tumors to develop in the breast and other organs. "At present, there is no good evidence that women using estrogen in the menopause have an increased risk of such tumors, but there is no way yet to be sure they do not; and one study raises the possibility that use of estrogens in the menopause may increase the risk of breast cancer may years later."
In a related action, the FDA porposed language for a user brochure for another class of hormones, the Progestins. Some doctors use them to test for pregnancy, but, the agency said, they many injure the fetus - needlessly, because "more rapid methods for testing for pregnancy are now available."
The drugs also have been used to prevent miscarriage, but, the FDA said, "no adequate evidence is available to show that they are effective." In addition, birth defects can occur if a woman takes the drugs during the first four months of pregnancy, the porposed brochure warns.
The drugs are sold under brand names including Delatutin, Duphaston, Norlutate, Norlutin and Provera.