FACT SHEET: FDA Initiates Removal of “Black Box” Warnings from Menopausal Hormone Replacement Therapy Products

Menopausal hormone therapies, also commonly referred to as hormone replacement therapy or (HRT), are approved to provide relief from common menopause symptoms, such as hot flashes and night sweats. Women may be under-utilizing approved therapies that can alleviate menopause symptoms and improve women’s health because of U.S. Food and Drug Administration (FDA) “black box” warnings about the risks associated with these drugs that the agency is removing.

About HRT

• HRT is FDA-approved for relief from common menopausal symptoms, such as hot flashes and night sweats (also known as vasomotor symptoms) and symptoms due to changes to the vagina, vulva, and urinary tract caused by decreased estrogen, also known as vulvovaginal atrophy or genitourinary syndrome of menopause. Some HRT products are also approved for the prevention of osteoporosis (bone weakening).
• Studies have provided evidence that starting HRT within ten years of the onset of menopause can have numerous benefits which for most women outweigh potential risks. Benefits include a reduced risk of all-cause mortality and fractures. HRT has also been associated with 50% reduction in heart attack risk, 64% reduction in cognitive decline, and 35% lower risk of Alzheimer’s.
• An analysis of 30 trials with 26,708 women participants found HRT was not associated with increased cancer mortality. In fact, women who start HRT before age 60 appear to have a decreased mortality risk.

Removal of “Black Box” Warnings

• The FDA is requesting that companies make changes to the labeling to provide current, accurate and balanced information about the benefits and risks of these drugs, so women, in consultation with their healthcare providers, can make the best decisions for their health.
• Specifically, the agency is working with companies to update language in product labeling 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 estrogen-alone products.
• Though the starting time of HRT and duration of use are decisions made between the prescriber and the individual patient, the FDA’s labeled recommendation will be to start HRT within 10 years of menopause onset or before 60 years of age for systemic HRT.
• This action follows the FDA’s assessment of the current relevant literature, including a reanalysis of data from younger cohorts of patients who initiated HRT within ten years of the onset of menopause.
• The FDA recently approved a generic version of Premarin (conjugated estrogens) tablets, a complex mixture of estrogens used to treat various conditions related to menopause and hormone deficiencies.
• The FDA has also approved non-hormonal medication for treating moderate to severe vasomotor symptoms, such as hot flashes.