F.D.A. Will Remove Black Box Warnings From Hormone Treatments for Menopause

Health|F.D.A. Will Remove Black Box Warnings From Hormone Treatments for Menopause

The Food and Drug Administration will remove the so-called black box warning from all hormone replacement products containing estrogen, Dr. Marty Makary, the agency’s commissioner, announced on Monday.

The labels will be rewritten with age-specific guidance indicating that there are long-term health benefits if treatment is begun within 10 years of the onset of menopause.

The changes, expected within six months, represent a radical turnabout in what women have been told about hormone replacement therapy.

In 2003, large government-run clinical trials concluded that hormone pills did not protect against heart disease or dementia, and in fact raised the risk of blood clots and breast cancer. Medical guidelines since then have told women to use hormones only sparingly for menopausal symptoms like hot flashes.

Dr. Makary, long a champion of the treatment, asserted on Monday that in fact hormones can reduce cardiovascular disease and cognitive decline, and can improve bone health in postmenopausal women.

“The long-term health benefits have been largely misunderstood,” Dr. Makary said. “Hormone replacement therapy may improve the health outcomes of women at a population level more than any other intervention, arguably, with the exception of antibiotics or vaccines.”

Asked whether hormone use was safe for all women, he added that any patient with a predisposition to blood clots or a history of breast cancer fueled by hormones should avoid it. He acknowledged that there may be other contraindications.

Critics opposed to removing the warning, the strongest kind the F.D.A. issues, had urged Dr. Makary to convene a scientific advisory panel to carry out a careful assessment of the evidence before making any changes to the label.

“Removing the black box and putting warnings in a lengthy label that many doctors and most patients will not read is taking women’s health backward,” Diana Zuckerman, a scientist and president of the National Center for Health Research, said on Monday.

“The claim that hormones for menopause is the best way to improve the health of women is inconsistent with years of research and will harm millions of women,” Dr. Zuckerman said. “There are many better ways to reduce the chances of osteoporosis, heart disease, cancer and dementia than hormone therapy for menopause.”

Hormone use has plummeted in recent decades. Even though estrogen is considered the most effective treatment for alleviating menopausal symptoms like hot flashes, night sweats and sleep loss, some doctors say that many women who could benefit avoid the treatment.

Hormone therapy has been used to relieve menopausal symptoms since the 1940s. By the 1980s, hormones were increasingly being prescribed to prevent cardiovascular disease and osteoporosis, as well, even in women well past menopause, despite concerns that the treatment might raise the risk of breast cancer.

The popularity of hormones was driven largely by observational studies indicating that hormones protected women from heart disease.

But large randomized trials subsequently tested this hypothesis, and concluded that there were no benefits to hormone replacement therapy in terms of heart attacks — and that it actually increased the risk of blood clots and strokes.

The trials also concluded that combined hormones — progestin and estrogen — in pill form increased the risk of breast cancer. But the danger to individual women was small, especially in early menopause, and there was no increase in breast cancer with estrogen alone, which lowered heart attack risk among women in their 50s.

Hormones also offered some benefits, reducing osteoporosis-related bone fractures and colorectal cancer.

Critics have questioned the conclusions and the methodology of the government-sponsored trials. Some of the risks were of borderline significance, they said, and women who wanted to reap long-term benefits from hormone treatment should initiate it soon after the onset of menopause.

Many doctors who treat menopausal women had pushed for removing the black box warning from local vaginal estrogen products, noting that these are low-dose products applied topically, not oral formulations. These physicians argued that studies have shown minimal to no systemic absorption of hormones from such products.

But the risks and benefits of long-term use of vaginal estrogens are still unclear, because the studies have been of limited duration, some experts say.

The black box label currently on estrogen products says that oral estrogen, with or without progestin, should not be taken to prevent heart disease and increases the risk of probable dementia in women 65 and older, as well as blood clots and strokes.

The label warning says that combined estrogen and progestin pills — a formulation used to offset the risk of uterine cancer — increases the risk of breast cancer.

The label notes, however, that these risks were found in trials of specific hormone formulations, and that the risks may not carry over to products with different formulations or to topically applied or low-dose products.