FDA Removes Boxed Warnings from Six Menopausal Hormone Therapies

The Food and Drug Administration on Thursday removed the most severe warnings related to breast cancer, cardiovascular disease and dementia from the labeling of half a dozen hormone therapies used for menopausal women. The commissioner announced plans to update the labeling in November in an effort to increase access to the treatments and reduce fears that have prevented women from seeking HRT treatments.

"Women face symptoms of menopause that can last for years, and our efforts will help these women make well-informed medical decisions," the commissioner said in a statement.

The decision to remove the "black box" warnings from hormone replacement therapies, or HRT, for menopause has been months in the making. At the FDA's request, 29 drug companies submitted proposed labeling changes.

HRT can be used to replenish hormones and relieve vasomotor symptoms, or hot flashes, associated with menopause. But various HRT treatments have not always been prescribed due to their black box warnings claiming an increased risk of cardiovascular events and cancers. Previous FDA labeling also warned of using estrogen for the prevention of cardiovascular disease and dementia.

Prior labeling was established after a major study conducted called the Women's Health Initiative that evaluated the use of estrogen plus progestin in postmenopausal women. The study was stopped early in 2002 after researchers identified an increased risk of heart disease and breast cancer. Another arm of the trial studying the use of estrogen only was also stopped early in 2004 after an observed increased risk of stroke.

However, other studies have identified mixed or even positive effects from using HRT, sparking debate about the risks and benefits of treatment. Some organizations and medical associations have supported broader use, but still warn of possible risks.

The commissioner held an informal panel in July to discuss the risks and benefits of HRT. The panel featured 12 experts of various medical backgrounds who held generally positive views of hormonal therapies and urged the FDA to change the labeling.

The commissioner said the agency would update labeling for several forms of hormone therapies for menopausal women following a "comprehensive review of the scientific literature."

A change in drug product labeling typically includes an FDA advisory committee tasked with rigorously reviewing and discussing new safety data. The FDA has stripped boxed warnings from six menopausal hormone therapies, bypassing the kind of lengthy advisory committee deliberations that usually precede such rare removals.

According to the FDA, randomized studies show that women who take HRT within 10 years of starting menopause before the age of 60 have a reduction in all-cause mortality and fractures.

The first group of treatments with new labeling includes products in systemic combination therapy, progestogen alone, systemic estrogen alone and topical vaginal estrogen.