For more than 20 years, menopausal hormone therapy (MHT) has carried a boxed warning about cardiovascular disease, breast cancer, dementia, and other serious health risks. This warning was based largely on findings from the Women’s Health Initiative (WHI) trial—specifically the arm studying oral conjugated equine estrogens (CEE) combined with medroxyprogesterone acetate (MPA).
It is critical to clarify what the WHI actually studied. The estrogen used was equine-derived, not human or bioidentical estradiol, and it was administered orally, combined with a synthetic progestin (MPA). Despite these very specific exposures, the concerning findings from this single formulation and route of administration were rapidly expanded by the FDA—without direct clinical evidence—to include all estrogen-containing hormone therapies, regardless of hormone type, dose, formulation, or route of administration.
The Problem With a One-Size-Fits-All Black Box
The boxed warning treats all hormone therapy products as if they pose identical risks. This includes local, nonsystemic therapies, such as low-dose vaginal estrogen, which have minimal systemic absorption. It also assumes that all women carry the same level of risk when using hormone therapy.
This approach does not support individualized care. In fact, it actively undermines it.
The black box warning is often the first—and sometimes only—thing patients see. Its stark language creates fear and confusion, making it difficult for clinicians to explain meaningful differences between hormone formulations, routes of administration, timing of initiation, and individual risk profiles. Rather than facilitating shared decision-making, the warning becomes a barrier to it.
The consequences have been profound. Since the early 2000s, hormone therapy use has declined by an estimated 70%–80%, even among women who are appropriate candidates—particularly those who are recently menopausal and experiencing significant symptoms.
Not All Hormone Therapies Are the Same
It is scientifically inaccurate to treat all hormone therapy formulations as equivalent in risk.
Low-dose vaginal estrogen is a clear example. It has minimal systemic absorption and is among the most effective treatments for genitourinary syndrome of menopause (GSM), improving vaginal dryness, dyspareunia, urinary symptoms, and recurrent urinary tract infections. It has never been shown to increase the risks listed in the boxed warning, yet it remains significantly underutilized because it carries the same alarming label as systemic therapies.
Similarly, transdermal estradiol, which is chemically identical to endogenous human estrogen, has a different metabolic and risk profile than oral estrogen. By bypassing first-pass hepatic metabolism, it is less likely to increase clotting factors and thrombotic risk. Despite these meaningful differences, transdermal and oral estrogens are treated identically in FDA labeling.
This lack of differentiation misleads patients and clinicians and discourages further research by falsely implying that all hormone therapies—regardless of formulation or route—carry equal risk.
Regulatory Inconsistency
Adding to the concern, just weeks ago the FDA issued a warning regarding an increased risk of meningioma associated with Depo-Provera (medroxyprogesterone acetate), a widely used hormone-based contraceptive.
Personalized Care Is Already Being Practiced
For years, many clinicians—particularly those practicing functional and integrative medicine—have treated women, and men, with hormone replacement therapy using careful, individualized assessments. These assessments commonly include detailed evaluations of personal and family medical history, cardiovascular and cancer risk, prior hormone-related side effects, and patient-specific goals.
Patients are appropriately educated about the FDA black box warning and the known risks and uncertainties of hormone therapy. Importantly, however, they are also given context and the opportunity to engage in shared decision-making with their physician. Rather than being driven by fear, patients are able to make informed decisions for themselves under medical supervision—precisely the model of care modern medicine strives to support.
Keeping the Focus Where It Belongs: Patients and Clinical Need
Even if renewed attention to hormone therapy labeling were, in part, motivated by the prospect of increased pharmaceutical revenue following decades of sharply reduced hormone therapy use, the central issue must remain patient care.
What matters most is that women and their physicians are able to make decisions based on clinical need, individualized risk assessment, and quality of life
For millions of women, menopausal symptoms are not trivial. Vasomotor symptoms, sleep disruption, genitourinary syndrome of menopause, mood and cognitive changes, and sexual dysfunction can cause significant and persistent distress, impair daily functioning, and diminish overall well-being. When appropriately prescribed, hormone therapy has the potential to meaningfully alleviate this burden.
A Better Path Forward: Evidence-Based, Personalized Labeling
Modern hormone therapy decision-making should be grounded in risk stratification and personalization, taking into account age, time since menopause, formulation, route of administration, dose, and individual health history.
Removing the boxed warning—while retaining clear, evidence-based information about risks and benefits in standard package labeling—would now allow women and physicians to engage in informed, nuanced conversations without the undue influence of a frightening and outdated warning.
The goal is not to promote hormone therapy indiscriminately or to ignore legitimate risks. The goal is accuracy.
Women deserve labeling that reflects contemporary science, acknowledges meaningful differences among hormone therapies, and supports shared decision-making rather than fear-based medicine rooted in outdated assumptions.
It is time to get hormone therapy labeling right.
