The Food and Drug Administration is requesting that manufacturers update labeling for hormone therapy products (estrogen and combination estrogen and progestin products) for use by postmenopausal women with data from WHIMS - The Women's Health Initiative Memory Study. WHIMS reported an increased risk of dementia in women 65 and older and showed that estrogen with progestin (Prempro) failed to prevent mild cognitive impairment (memory loss). (WHIMS is a substudy of the Women's Health Initiative (WHI) conducted by the National Institutes of Health.)
The suggested updated labeling and a revised labeling guidance include information about current approved uses of the drugs: estrogen and combined estrogen with progestin products are effective for treating moderate to severe hot flashes and night sweats, moderate to severe vaginal dryness, and prevention of osteoporosis associated with menopause. The suggested label states that if these products are prescribed solely for vaginal symptoms, health care providers are advised to consider the use of topical vaginal products. The suggested label recommends that if the products are prescribed for osteoporosis, women should be at significant risk for osteoporosis and non-estrogen treatments should be considered inappropriate.
FDA is also advising women and their health care providers that hormone therapy has never been approved for prevention of cognitive disorders such as Alzheimer's disease or memory loss.
"Postmenopausal women need to know about recent results of the Women's Health Initiative, because this information can have a significant public health impact," said FDA Commissioner Mark McClellan, M.D., Ph.D. He added, "After thoroughly evaluating the WHIMS data, FDA is updating the risk and benefit information in product labels to help women and health professionals make informed choices about hormone therapies."
FDA advises women to talk with their health care providers, and if they decide that hormone therapy is appropriate, they should use the lowest effective dose of for the shortest duration to reach treatment goals.
The results of the WHIMS study were published in May 2003 in the Journal of the American Medical Association (JAMA). The study included 4,500 (of the 16,000) WHI participants women between 65 and 79 years of age; half were taking Prempro and half were on placebo.
Sixty women were diagnosed with dementia. Of these, 39 (65%) were in the estrogen with progestin group and 21 (35%) were in the placebo group. Although these findings are statistically significant, the risks to individual women are small. Participants in the study were at least 15 years older than the typical newly menopausal woman. FDA is working with manufacturers to add the WHIMS data to the labels of these drugs and at the same time, the agency is releasing its updated labeling guidance for industry, which includes the revised information.
- Manufacturers should include WHIMS data in the existing Black Box that contains WHI data on cardiovascular risks based on the WHI study. WHIMS found an increased risk of developing probable dementia in postmenopausal women age 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate compared to placebo. It is unknown whether this finding applies to younger postmenopausal women taking estrogen alone.
- FDA also advised manufacturers to add the WHIMS data to the clinical studies section.
- Additional information being added from WHI about mammography includes: "The use of estrogen with progestin may result in an increase in abnormal mammograms requiring further evaluation."
- Manufacturers must specify the lowest effective dose or state that the lowest dose of their drug has not been determined.
FDA will include this new information in the educational materials developed for the "Menopause and Hormones Information Campaign" that was launched last fall. FDA will also continue to engage the National Institutes of Health as well as manufacturers to pursue research on questions addressing the safe and effective use of estrogen with progestin therapies.
Source: FDA Press Release #P04-18, February 10, 2004