For nearly a quarter of a century, the standard medical advice for menopausal symptoms was a near-universal no. On 17 July 2002, a US trial of 16,608 postmenopausal women aged 50 to 79 was stopped early because the harms of combined hormone therapy appeared to exceed the benefits [1]. Within months, prescriptions collapsed, regulators imposed the harshest caution labels available, and a generation of women was steered away from the most effective treatment for hot flashes, night sweats and the genitourinary symptoms of menopause. Twenty-three years later, on 10 November 2025, the US Food and Drug Administration (FDA) moved to undo that warning, in a regulator-led reversal that, in the words of Commissioner Marty Makary, has its roots in "a distortion of risk" [2]. The reversal is, on the evidence, a long-overdue correction. It is also incomplete, contested, and not yet matched by access on the ground.
The 2002 study that ended a generation of treatment
The original Women's Health Initiative (WHI) trial, led by Jacques Rossouw and published in JAMA on 17 July 2002, randomised 16,608 women with a uterus to combined conjugated equine estrogens (CEE) 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg daily, or placebo. The mean age of participants was 63, more than a decade older than the average age of menopause onset in the United States, which is 51 [1]. After 5.2 years, the data and safety monitoring board halted the combined-hormone arm. The published findings: increased risk of breast cancer (HR 1.26), coronary heart disease events (HR 1.29), stroke (HR 1.41) and pulmonary embolism (HR 2.13), with reduced risk of colorectal cancer (HR 0.63) and hip fracture (HR 0.66) [1].
In 2003, the FDA imposed a black box warning on all systemic estrogen products, the agency's strongest caution, listing risks of breast cancer, blood clots, stroke and dementia. The warning has remained on every pill, patch, cream and spray containing estrogen for the past 22 years [2]. Use of hormone therapy in the United States fell from approximately 40% of postmenopausal women in 1999 to approximately 5% in 2020, per JAMA Health Forum data cited by USA Today [2]. The Menopause Society reported in 2024 that prescribing rates have only partially rebounded, with current use around 4 to 5% [3].
The scientific correction: timing, formulation, and the JAMA reanalysis
The argument that the 2002 WHI had been over-read is not new. By 2024, the WHI investigators themselves, writing in JAMA, were formalising it. JoAnn Manson and colleagues concluded that, when hormone therapy is initiated close to the time of menopause, the benefit-risk profile is more favourable than when it is initiated in older women [4]. In stratified analyses, the cardiovascular and mortality benefits of menopausal hormone therapy (MHT) emerged primarily in women who started treatment within 10 years of menopause onset, a finding now widely known as the "timing hypothesis".
What had driven the original adverse signal was participant age. The WHI cohort's mean age of 63 placed most women well outside the window in which MHT appears to be most beneficial. The same reanalyses flagged a second methodological point: the WHI used a specific oral combination, CEE plus MPA, at a fixed dose. A 2015 systematic review and meta-analysis by Vinther and colleagues in the Journal of Clinical Endocrinology & Metabolism found that oral estrogen was associated with increased risk of venous thromboembolism (VTE) compared with transdermal estrogen, and that transdermal estradiol patches at doses of 50 micrograms or less did not carry the same VTE signal [5]. A 2024 analysis of WHI cardiovascular biomarkers, led by Matthew Nudy of Penn State Hershey Medical Center, found that both CEE alone and CEE plus MPA improved most cardiovascular biomarkers relative to placebo: HDL cholesterol increased by 13% (CEE) and 7% (CEE+MPA), LDL cholesterol fell by about 11% in both arms, and lipoprotein(a) decreased by 15% and 20% respectively [6]. The one biomarker that worsened was triglycerides.
These findings underwrote the consensus codified in the major society statements. According to the International Menopause Society (IMS) 2024 White Paper, the benefits of MHT generally outweigh the risks for symptomatic women under 60 years of age or within 10 years of the onset of menopause, with dose, route of administration, and choice of progestogen all clinically important variables [7]. Endorsing the same framework, the 2022 position statement of The North American Menopause Society noted no arbitrary upper limit on duration of MHT for women with persistent symptoms and a favourable risk profile [8]. NICE in the UK updated its NG23 guideline in November 2024 to recommend hormone replacement therapy (HRT) as first-line for vasomotor symptoms and to prefer transdermal estrogen for women at higher VTE risk, including those with obesity [9].
The November 2025 FDA pivot
The regulatory action that consolidated this body of evidence came on 10 November 2025. Commissioner Makary, Health and Human Services Secretary Robert F. Kennedy Jr, and the agency's senior leadership announced that the FDA was asking drug manufacturers to remove the black box warning from systemic estrogen products and to update labels to reflect current evidence [2]. Product-specific safety information would remain, but the disproportionate top-of-label caution, in place since 2003, was to come off.
In a JAMA Viewpoint published the same day, Makary, Sara Brenner and Peter Marks framed the move as a re-evaluation of the 2003 decision that had been "driven by initial Women's Health Initiative findings" [10]. STAT News reported that Makary had previewed the reversal in a Wall Street Journal op-ed, characterising two decades of prescribing caution as a "medical dogma" that had "led to millions of women being denied the benefits of hormone therapy" [11]. At a summer 2025 FDA advisory panel, physicians including Heather Hirsch of Brigham and Women's and urologist Rachel Rubin had testified in favour of removing the warnings. "The label was outdated and harmful," Hirsch said. "It led to so many women not getting the care they need" [2]. The obstetrician-gynaecologist Corinne Menn, who practises with Alloy, added that the boxed fear "got in the way of patients being able to trust what their physicians were telling them" [2].
The FDA's recommendation was that hormone therapy should generally start within 10 years of menopause onset, or before age 60 [2]. Going further still, the 2024 IMS White Paper recommends against routine discontinuation at 65 [7].
The knowledge gap revealed
If the 2025 FDA action was the regulatory pivot, the 2026 evidence on what women actually know about menopause is the corrective on the other side of the consultation room. A global digital study by Mayo Clinic and the women's health app Flo Health, published in the journal Menopause on 28 January 2026, analysed responses from 17,494 Flo users across 158 countries, with data collected between December 2024 and May 2025 [12]. Women aged 18 to 34 completed knowledge and attitudes modules; women aged 35 and over completed additional modules on symptoms, healthcare interactions and treatment experiences.
Asked to identify symptoms they associated with perimenopause, 71% of women named hot flashes, 68% named sleep problems and 65% named weight gain, the visible trio. Awareness dropped sharply for fatigue, irritability and digestive changes, even though those symptoms were among the most frequently reported in the 35-and-over modules [12]. United States respondents ranked only sixth globally for perimenopause knowledge, behind the UK, Ireland, Canada, Australia and the Netherlands. First place went to the UK, a finding Future Fem Health attributed in part to the "Davina effect" from Davina McCall's menopause documentary driving HRT interest [13]. Lowest knowledge scores were in Nigeria, France and parts of Latin America [12].
For Anna Klepchukova, Flo Health's chief medical officer and the study's lead author, the implication is straightforward: "We need to normalise conversations around perimenopause and menopause, so women feel empowered to have honest conversations with their doctors and other support systems" [12]. The 2026 Nature feature by Heidi Ledford, "The missing pieces of menopause science", published 6 March 2026, makes a parallel point from the research side: decades of underfunding and the historical exclusion of women from cardiovascular and other clinical trials have left menopause understudied, and the pipeline of non-hormonal therapies, including the neurokinin 3 receptor (NK3R) antagonist fezolinetant, is still narrow [14].
The policy shift reshaping UK, US and Australian menopause care
The regulatory pivot in the United States has been matched, in different ways, on three policy fronts.
In the United Kingdom, the Department for Business and Trade issued updated menopause-in-the-workplace guidance on 4 March 2026, formalising employer responsibilities to consider reasonable workplace adjustments, including temperature control, flexible working, access to rest facilities and manager training [15]. The guidance implements provisions of the Employment Rights Act 2025, which phased in new protections that bring menopause within the existing workplace equality framework. An NHS Confederation 2024 study estimated that 60,000 women in the UK are unemployed because of menopausal symptoms, with an annual economic impact of about £1.5 billion (US$2 billion) [16]. Roughly one in two women in Great Britain aged 45 to 65 go through menopause without consulting a medical professional, per an Ipsos MORI survey for the British Menopause Society [16].
In Australia, the federal government introduced a new Medicare rebate for menopause health assessments on 1 July 2025, funded as part of the "More choice, lower costs and better health care for women" initiative and shaped by the 2024 Parliamentary Inquiry into Menopause and Perimenopause [17]. One in five Australian women experience menopausal symptoms severe enough to interfere with daily life, according to the Department of Health [17]. The TGA and the Australasian Menopause Society have warned that supply shortages of PBS-listed MHT products are ongoing, undermining the transdermal-first approach the IMS and NICE recommend [18][19].
In the United States, the JAMA Viewpoint by Makary, Brenner and Marks is the durable signal: the agency's own medical-journal rationale for the reversal will inform clinical practice guidance for years [10]. The 2024 Nudy cardiovascular biomarker analysis and the 2024 JAMA review by Manson and colleagues provide the US evidence base [4][6].
What women in perimenopause and early menopause should actually know in 2026
The 2026 consensus, drawn from the IMS 2024 White Paper, the 2022 North American Menopause Society position, the 2024 NICE NG23 update, and the November 2025 FDA action, can be summarised in six points. First, MHT remains the most effective treatment for vasomotor symptoms and for the genitourinary syndrome of menopause [7][8][9]. Second, the best window for starting systemic MHT is within 10 years of menopause onset or before age 60, the timing-hypothesis window the FDA, IMS and Menopause Society all endorse [2][7][8]. Third, transdermal estradiol plus micronised progesterone is generally preferred for women at higher VTE or stroke risk; medroxyprogesterone acetate, the progestin used in the original WHI, is increasingly displaced in many current guidelines by micronised progesterone and other progestogens with more favourable risk profiles [5][7][9]. Fourth, there is no arbitrary cap on MHT duration; the 2022 NAMS position and the IMS 2024 White Paper recommend regular individualised reassessment of the benefit-risk balance [7][8]. Fifth, vaginal estrogen for genitourinary symptoms can be used at any age and, because of its localised action, is generally regarded as carrying a different risk profile from the systemic formulations to which the 2003 boxed warning applied [8]. Sixth, women should still be counselled on personalised breast cancer and cardiovascular risk; the November 2025 FDA action is not a declaration that MHT is risk-free, it is a declaration that the original 2003 warning was disproportionate to the modern evidence base [2][10].
The honest-uncertainty side of this story is also the optimistic side. The November 2025 FDA action does not mean MHT is risk-free, and it does not mean the 2002 WHI was wrong on its own terms. It means that one trial, in a cohort with a mean age a decade older than menopause onset, was over-generalised into a generation of clinical caution. Twenty-three years on, the regulatory, scientific and policy machinery of menopause care is, finally, catching up with the evidence. The work that remains, on access and supply, is the part no boxed warning can solve.