The Truth About the Black Box Warning on Menopausal Hormone Therapy: What the Change Really Means
For more than two decades, menopausal hormone therapy (MHT) has carried a black box warning — the most serious caution the FDA places on a medication. For many women, this warning shaped their fears, influenced their doctors, and dramatically limited access to a therapy that can be life-changing when used appropriately.
Now, with the FDA removing the black box warning from most forms of estrogen therapy and adjusting the language around risk, many women are asking:
What does this mean? Should we trust these changes? And how should we move forward?
As a neurologist specializing in women’s brain health, here’s my perspective:
What Is a Black Box Warning?
A black box warning is the strongest type of safety warning issued by the FDA. It is placed on medications when there is evidence of potentially serious risks.
For menopausal hormone therapy, the warning was added in 2003 after early findings from the Women’s Health Initiative (WHI) suggested increased risks of:
Breast cancer
Stroke
Coronary artery disease
Blood clots
Although later research clarified and, in many cases, reduced these concerns, the warning remained in place for decades.
Why Was the Original Warning Established?
The WHI was a landmark study, but its findings were misinterpreted, exaggerated and overly generalized, leading to fear and decades of under-treatment. The study participants were, on average, 63 years old, many more than a decade past menopause (age 51 in the US) — a group for whom starting oral estrogen does carry higher risks.
But younger women (40s–50s) starting MHT close to menopause were not the population driving the concerning risk signals. Later analyses also clarified that:
Breast cancer risk was small (less than 1 in a 1000), and in the estrogen-only arm, breast cancer risk was actually lower.
Stroke and clotting risks were associated primarily with oral estrogen, not transdermal forms.
Cardiovascular risks were highest when starting therapy late in menopause — not early.
Cognitive decline appeared increased only in women 65+ years starting estrogen for the first time.
Despite these nuances, the warning remained broad, frightening, and nonspecific — discouraging use even for women for whom the benefits clearly outweighed the risks.
Why the Warning Was Changed — And Should We Trust It?
Some voices have framed this as a political or administrative issue. Emotion is running high. I’ve seen extreme statements, from “the government wants women harmed” to “now anything goes.” Neither is true.
My perspective is that no one should prescribe a therapy unless they have personally seen — and understand — how that therapy’s risks present in real human beings. In my own clinical work I’ve seen both sides of menopausal hormone therapy — the profound benefits it can offer when used appropriately, and the serious adverse events that can occur when it is not, including stroke, myocardial infarction, and worsening vascular risk.
That requires clinical training, judgment, and lived experience. It cannot be replaced by an online course, a weekend seminar, or mid-level protocols designed for high-volume care.
The updated FDA guidance reflects 20+ years of new data, much of it showing that the original warnings overstated or misattributed risk. The change does not mean MHT is risk-free — only that the warning now better matches the evidence. At the same time, some recent FDA statements have leaned toward overly optimistic messaging that minimizes the complexity of MHT safety and may give the false impression that risks are negligible or universally offset by benefits.
What Should We Expect From This Change?
The Risk: Overprescribing Without Nuance
This is my biggest concern.
With the stigma reduced, some clinicians — especially those without deep training in midlife whole-systems physiology — may prescribe hormone therapy without appropriate evaluation. The result?
Misuse of oral estrogen in women with vascular risk
Inadequate baseline metabolic and cardiovascular assessments
Missed contraindications
Increased risk of stroke, clotting, or CAD when prescribed to the wrong patients
Potential backlash: if adverse events rise due to careless prescribing, we risk another pendulum swing toward fear, restriction, and misinformation — setting women’s health back another decade
MHT is powerful. It needs respect, not fear — and not casual prescribing.
The Benefits:
Improved Physician Acceptance
Many clinicians who previously avoided MHT entirely may now gain confidence to learn more:
Better education in medical training
More comfort discussing symptoms
Less stigma
More referrals to specialists
This is excellent for women.
2. More Research Investment
One of the most meaningful potential benefits of the black box removal is the opportunity for renewed scientific investment in menopausal hormone therapy — especially as it relates to brain health.
For two decades, the fear generated by the WHI halted or slowed entire areas of research. Grant funding dried up, industry investment stalled, and many academic centers avoided menopause research altogether because the topic felt “too controversial.” As a result, we lost critical time that could have been spent understanding how estrogen interacts with the brain, metabolism, and aging.
But this shift — paired with a cultural “menopause moment” — is already beginning to change the landscape.
What expanded research could mean:
Better understanding of estrogen’s role in brain energy metabolism.
Emerging imaging studies show estradiol affects glucose utilization, mitochondrial efficiency, and resilience of neural circuits — especially in women at genetic risk for Alzheimer’s.
More clarity on the timing hypothesis.
We need rigorous trials to define which women benefit most from therapy started in early perimenopause versus early postmenopause, and how timing influences long-term cognitive trajectories.
Improved insight into individualized risk.
Research could help us refine how genetics (ApoE status, CYP metabolism), vascular health, sleep disorders, metabolic markers, and inflammatory phenotypes interact with MHT safety and benefit.
Better progestogen science.
Not all progestogens are the same. We need studies distinguishing micronized progesterone from synthetic progestins in terms of breast cancer risk, vascular safety, and brain effects.
Potential therapeutic advances for dementia prevention.
If MHT — started at the right time, in the right dose, and in the right formulation — influences amyloid processing, tau phosphorylation, or synaptic plasticity, the implications for women’s long-term neurologic health are enormous.
New delivery systems and formulations.
With fear reduced, pharmaceutical innovation may return, leading to safer routes, personalized dosing, and combination therapies that target both symptoms and long-term health.
3. Better Health Outcomes
Millions of women have suffered silently for years.
A more balanced risk message may encourage:
Earlier diagnosis of perimenopause resulting in proactive intervention
Better quality of life
Better long-term brain and cardiometabolic health outcomes
4. Improved Social and Economic Outcomes
Untreated menopausal symptoms affect:
Work performance, promotion and productivity ($1.8 billion per year in lost work time, according to a Mayo Clinic study.)
Relationships, marital and family stability
Mental health and happiness
Community involvement
When women feel better, families, workplaces, and communities thrive.
How Do We Prevent the Downsides?
1. Patients and clinicians must be informed — not fearful.
Knowledge, compassion and curiosity as clinicians protects patients better than any warning label.
2. Care must be individualized.
There is no one “right” hormone treatment. Timing, dose, route, and personal risk factors matter.
3. Treatment should come from experts.
Preferably clinicians who have the training and experience to navigate the complex decision-making required when considering menopausal hormone therapy within the broader context of whole-person care — including cardiometabolic health, vascular risk, and long-term brain health.
What Do We Actually Know About the Risks?
A brief evidence-based overview:
Breast Cancer
Estrogen-only therapy reduced breast cancer risk in the WHI.
Combined estrogen + progestogen therapy slightly increased risk after >5 years, but the absolute risk was small (<1 in 1000 new cases of breast cancer)
Different progestogens carry different risk profiles.
Stroke
Elevated risk is primarily associated with oral estrogen.
Transdermal estrogen at physiologic doses has not shown the same risk profile.
Coronary Artery Disease (CAD)
Starting MHT early in menopause may be cardioprotective (“the timing hypothesis”).
Starting it late, especially orally, can increase cardiovascular events. It’s important to understand a woman’s cardiovascular risk profile before starting MHT.
Dementia
Starting MHT after age 65 increased dementia risk in the WHI Memory Study.
But newer studies show that timely, individualized estradiol use may support brain metabolism and memory — particularly in APOE4 carriers.
My Perspective as a Neurologist Specializing in Women’s Brain Health
What I’m Seeing
Women prescribed oral estrogen at 55+ without metabolic evaluation
Increasing use of hormone pellets with supraphysiologic dosing
Lack of adequate cardiovascular or cerebrovascular risk assessment before prescribing
Overlooking sleep apnea, insulin resistance, or hypertension — all major modifiers of MHT safety
Underrecognition that menopausal symptoms are neurologic as much as hormonal
What I Do in My Practice
I take a prevention-focused, neurologically informed, data-driven approach:
Comprehensive metabolic, cardiovascular, and cerebrovascular risk profile consideration
Preference for transdermal estradiol unless contraindicated
Thoughtful progestogen (and testosterone) use when needed
Ongoing monitoring
Education on lifestyle, supplements, and non-hormonal options
A whole-body, systems-based view of women’s midlife physiology
Why I Practice Differently
Menopause isn’t just about hot flashes, shifting hormones or symptom relief. It represents a critical inflection point in a woman’s long-term neurologic trajectory. This transition affects brain metabolism, cardiovascular aging, glucose regulation, sleep architecture, mood circuits, cognitive resilience, and overall neurologic health, often years before symptoms become obvious. Supporting women through this period requires expertise and nuance, prevention-focused thinking, and a commitment to seeing the entire woman: her risks, her goals, and the future brain she hopes to protect.
Final Thoughts
The removal of the black box warning is not a green light to prescribe blindly, nor is it evidence of political manipulation. It is recognition that the science has evolved, and that women deserve accurate information, not fear.
We move forward best when we move forward informed — with expertise, humility, nuance, and partnership between patient and clinician.
