United States of America - The Food and Drug Administration (FDA) is advising women and health care professionals of important new safety changes to labelling of all estrogen and estrogen with progestin products for use by postmenopausal women. These changes reflect FDA’s analysis of data from the Women’s Health Initiative study (WHI), a landmark study sponsored by the National Institutes of Health that has raised concerns about risks of using these products.

The FDA will also be issuing updated guidances for manufacturers of estrogen and estrogen with progestin products regarding labelling of those products and development of new products for use in postmenopausal women. Changes include a boxed warning that reflects new risk information and changes to the approved indications to emphasize individualized decisions that appropriately balance the benefits and the potential risks of these products.

The WHI study has several components, one of which was designed to assess the effects of Prempro®, a combination of estrogens plus a progestin, on the risk of developing heart disease. The Prempro® arm of the WHI was halted early in July 2002 because the overall health risks, particularly the risks of invasive breast cancer and cardiovascular disease, exceeded the benefits of the drug. Estrogen and progestin hormones have never been approved by FDA for prevention of heart disease, although physicians could prescribe them “off-label” for this use.

All other manufacturers of estrogen and estrogen with progestin drug products for use in postmenopausal women have been requested to make similar changes to the labelling for their products. It is estimated that about ten million postmenopausal women in the USA currently use estrogen and combination estrogen with progestin products for relief of menopausal symptoms and prevention of postmenopausal osteoporosis.

Estrogen products are approved for use in relieving vasomotor symptoms of menopause such as “hot flashes” and night sweats; symptoms of vulvar and vaginal atrophy such as dryness, itching, and burning; and prevention of postmenopausal osteoporosis. Because there are few alternatives for the relief of severe vasomotor symptoms and severe symptoms of vulvar vaginal atrophy, estrogens and estrogens with progestins have an important role in women’s health.

Health care providers are advised to prescribe estrogen and combined estrogen with progestin drug products at the lowest dose and for the shortest duration for the individual woman. After discussing treatment with their doctor, women should have yearly breast exams by a health care provider, perform monthly breast self-examinations, and receive periodic mammography examinations based on age and risk factors. Other ways to reduce risk factors for heart disease (e.g., high blood pressure, poor diet, tobacco use) and osteoporosis (e.g., an appropriate diet, use of Vitamin D and Calcium supplements, weight-bearing exercise) should be proposed.

Reference: FDA News, P03-1 2003.