The US Department of Health and Human Services (HHS) has announced plans to remove long-standing boxed warnings from hormone replacement therapy (HRT) products used to treat menopause.
The move marks a significant regulatory shift for the women’s health sector.
The FDA has begun the process of withdrawing the broad “black box” warnings that have been in place for more than 20 years, a move the agency says reflects updated evidence on the safety and clinical use of HRT.
The decision was outlined at a press briefing held at HHS headquarters, attended by FDA Commissioner Dr Marty Makary, HHS Secretary Robert F. Kennedy Jr and senior government officials.
Women have used HRT products for decades to relieve menopausal symptoms.
However, their use plummeted in the early 2000s when the FDA applied boxed warnings following a Women’s Health Initiative study that found a statistically non-significant increase in the risk of breast cancer diagnosis.
The average age of women in the study was 63 years — more than a decade past the average age of a woman experiencing menopause — and study participants were given a hormone formulation no longer in common use.
The FDA is initiating the removal of the boxed warnings following a comprehensive review of the scientific literature, an expert panel in July and a public comment period.
The agency is working with companies to update language in product labelling to remove references to risks of cardiovascular disease, breast cancer and probable dementia.
The FDA is not seeking to remove the boxed warning for endometrial cancer for systemic oestrogen-alone products.
“Today, we are standing up for every woman who has symptoms of menopause and is looking to know her options and receive potentially life-changing treatment,” said Secretary Kennedy.
“For more than two decades, bad science and bureaucratic inertia have resulted in women and physicians having an incomplete view of HRT."
"We are returning to evidence-based medicine and giving women control over their health again.”
“Tragically, tens of millions of women have been denied the life-changing and long-term health benefits of hormone replacement therapy because of a medical dogma rooted in a distortion of risk,” said FDA Commissioner Makary.
“For too long, issues of women’s health have been underrecognised. Women and their physicians should make decisions based on data, not fear.”
As women go through menopause, the ovaries produce less oestrogen and progesterone.
FDA-approved HRT containing oestrogen and progesterone (or oestrogen alone as indicated for postmenopausal women without a uterus) can restore these declining hormones and relieve symptoms such as hot flashes, night sweats, sleep disturbances and bone loss.
“Oestrogen is a key hormone for women's health. Every single part of a woman's body depends on oestrogen to operate at its best — including the brain, bones, heart and muscles,” said Advanced Research Projects Agency for Health Director Dr Alicia Jackson.
“The removal of the black box warning, based on the best science and data, is an incredible step forward to empower millions of women to live longer, healthier lives.”
“Someday, science will help us slow or reverse all the damage of ageing,” said Health and Human Services Deputy Secretary Jim O’Neill.
"A good, safe way to address oestrogen depletion already exists and today, Secretary Kennedy and Commissioner Makary are removing a barrier to this treatment."
"Many more women can reduce their risk of fracture, heart disease and immune and cognitive decline while extending their vigour.”
Randomised studies show that women who initiate HRT within ten years of the onset of menopause (generally before age 60) have a reduction in all-cause mortality and fractures.
Women may also reduce their risk of cardiovascular diseases by as much as 50%, Alzheimer’s disease by 35% and bone fractures by 50 to 60%.
Though the starting time of HRT and duration of use are decisions made between the prescriber and the individual patient, the FDA’s labelled recommendation will be to start HRT within ten years of menopause onset or before 60 years of age for systemic HRT.
In addition to the removal of boxed warnings, the FDA is also approving two new drugs to expand treatment options for menopausal symptoms.
The first is the approval of a generic version of Premarin (conjugated oestrogens), the first such approval in more than 30 years for this widely used hormone replacement therapy.
The new generic product is expected to improve affordability and access while maintaining the same quality, safety and effectiveness as the brand-name drug.
The second approval is for a non-hormonal treatment for moderate to severe vasomotor symptoms, such as hot flashes, associated with menopause.
This option provides relief for women who cannot or choose not to use hormone therapy.