The Department of Health and Human Services (HHS) and the FDA have conducted an in-depth review of the scientific evidence and have decided to remove the former “black box” warnings that had accompanied many hormone treatments since 2002.
For more than 20 years, those black boxes warned of a possible increased risk of heart attack, stroke, thrombosis, breast cancer, and dementia in all women using estrogen, regardless of age, timing of treatment initiation, or the type of hormone used. These warnings were largely based on early results from the well-known Women’s Health Initiative (WHI) study, conducted in women over 60 years of age, many with pre-existing cardiovascular disease, and using hormone preparations that are now largely obsolete.
Dr. Sánchez – Neolife Medical Team
What exactly has the HHS/FDA decided?
After reviewing decades of clinical studies and meta-analyses, the HHS concluded that these generalized warnings did not reflect current scientific knowledge and may have discouraged many women from receiving a treatment beneficial to their health.
The key changes include the removal of “black box” warnings from multiple systemic estrogen and estrogen–progestogen preparations. Package inserts still include warnings, but no longer as a global, alarmist message for all women. It is also stated that in women under 60 years of age or within 10 years of menopause, the overall evidence from clinical trials indicates that hormone therapy reduces coronary heart disease events and overall mortality, markedly lowers the risk of osteoporotic fractures, and may reduce cognitive decline and Alzheimer’s disease when initiated close to menopause (the so-called “window of opportunity”), although debate remains in this area. In addition, the FDA has created a dedicated expert panel on menopause and Menopausal Hormone Therapy (MHT) to update information for patients and healthcare professionals and to continue reviewing the evidence on an ongoing basis.
In summary, the official message has shifted from “avoid it unless absolutely necessary and for the shortest possible time” to “for many younger postmenopausal women, the benefits may clearly outweigh the risks when therapy is properly indicated and supervised.”
What evidence supports this new perspective?
As mentioned, the data review includes meta-analyses of clinical trials showing that women who start Menopausal Hormone Therapy before age 60 or within 10 years after menopause experience a 30% reduction in coronary heart disease and a 30–40% reduction in all-cause mortality compared with placebo. Trials in women with recent menopause (such as the Danish DOPS study and others) were also included, showing fewer cardiovascular events and fewer fractures in women treated with estrogen compared with untreated women. In addition, observational and neuroimaging studies were considered, suggesting a lower amyloid/tau burden or reduced dementia risk when therapy is initiated close to menopause, although results are not uniform and research is ongoing.
All of this has strengthened the “timing” or window-of-opportunity hypothesis: the effects of hormones depend greatly on when they are started (age and years since the last menstrual period) and on the type of estrogen and progestogen used.
It is also important to note that modern menopausal hormone therapy is based on the use of bioidentical hormones, primarily progesterone and estradiol, which are not equivalent to the synthetic hormones commonly referred to as progestins and estrogens that were also included in many of these studies. This distinction is critical, as many historical risks associated with hormone therapy stem from the use of progestins (such as Provera) or conjugated estrogens (such as Premarin), which are very different from the biological profile of molecules that the human body naturally produces or recognizes, such as bioidentical hormones.
The superiority of bioidentical hormones lies in the fact that the body recognizes them as its own, allowing them to exert specific effects on human receptors without significant off-target activation of unwanted pathways. In contrast, progestins and commercially available “progestogens” may also bind to androgenic or mineralocorticoid receptors, generating side effects.
Do risks still exist?
Yes, depending on the type of hormone, the route of administration, and the individual woman’s characteristics. Some hormones may increase the risk of venous thrombosis and stroke, particularly in older women, smokers, those with obesity, or those with pre-existing risk factors, and especially with high-dose oral estrogens.
Certain regimens combining estrogen with specific synthetic progestogens may slightly increase the risk of breast cancer after several years of continuous use. This is why choosing estradiol and progesterone in a balanced way, along with appropriate monitoring, is essential. The decision to treat a particular woman must remain individualized, taking into account personal and family history.
In fact, several experts have warned that enthusiasm for potential cardiovascular and neurological benefits should not be interpreted as a “free pass” to prescribe hormones to any woman. Consulting a healthcare professional who is experienced and up to date in this field remains essential.
What does this mean for you as a patient?
At Neolife, transparency and scientific rigor are central to how we share information with our patients, and we believe this update opens the door to more honest and nuanced conversations. If you are in perimenopause or within the first 10 years after menopause and experience bothersome symptoms (hot flashes, insomnia, vaginal dryness, mood changes) or have risk factors for osteoporosis, we can evaluate Menopausal Hormone Therapy not only as a symptomatic treatment but also as part of a long-term prevention strategy. Even if many years have passed since menopause, or if you have a history of thrombosis or hormone-dependent cancer, we will likely prioritize other treatment options, as the type of therapy (oral, transdermal, vaginal), dosage, and whether or not to combine with progesterone must be decided on a case-by-case basis after careful assessment.
Our approach at Neolife integrates these new recommendations with a thorough evaluation of personal and family history, as well as complementary studies. We favor bioidentical estradiol and micronized progesterone, which are the most extensively studied molecules and generally have the best safety profile. We also maintain close follow-up with each patient, with regular reviews to assess efficacy, potential side effects, and changes in risk factors, alongside lifestyle guidance.
In conclusion, the decision by the HHS and the FDA to remove the former “black box” warnings finally acknowledges what we at Neolife have long understood through continuous scientific updating: that current evidence paints a very different picture from that of 2002, and that when properly indicated and initiated at the right time, hormone therapy is a powerful tool not only for symptom relief but also for protecting bone and cardiovascular health in many women—adding more life to years.
If you are at this stage of life and have questions, we encourage you to reach out to us. The most important thing is to discuss it with a professional trained in hormone therapy, who can explain options, benefits, and risks transparently, and help you decide together what is best for you.
BIBLIOGRAPHY
(1) S. Department of Health and Human Services. (2024).
(2) Food and Drug Administration. (2025). FDA expert panel on menopause and hormone replacement therapy for women, 07/17/2025. FDA Expert Panels.
(3) Danish Osteoporosis Prevention Study (DOPS)