Dear Editor,
A black box warning is the United States Food and Drug Administration’s (FDA) most stringent safety alert, displayed prominently in bold text within a black-bordered box on drug packaging to highlight serious or life-threatening risks, often restricting use. On 10 November 2025, the FDA announced the initiation of the removal of these warnings from all menopausal hormone therapy (MHT) products, including systemic and low-dose vaginal preparations, citing outdated interpretations of early Women’s Health Initiative (WHI) findings that overstated risks in older women [1]. Imposed in 2003 following early termination of the WHI combined therapy arm, the warnings cautioned against risks of cardiovascular disease, stroke, breast cancer, and probable dementia in postmenopausal women aged 50–79 years using oral conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg daily, where overall health risks exceeded benefits over an average 5.2-year follow-up in healthy postmenopausal U.S. women[2].
Extended WHI follow-up and contemporary evidence now show that risks are markedly lower when MHT is initiated in women younger than 60 years or within 10 years of menopause. In this group, combined and estrogen-only MHT demonstrate no significant increase in coronary heart disease (HR 0.94, 95% CI 0.78–1.14) or breast cancer (HR 0.79, 95% CI 0.65–0.97 for estrogen-only), with significant reductions in all-cause mortality and osteoporotic fractures[3]. Low-dose vaginal estrogen, widely used for genitourinary syndrome of menopause, has negligible systemic absorption and no increased risk of endometrial or breast cancer (Cochrane meta-analysis of 30 RCTs)[4]. The North American Menopause Society 2022 position statement and recent international guidelines endorse MHT as first-line therapy for bothersome vasomotor symptoms and prevention of osteoporosis in appropriately selected women[5].
In South Asia, where early menopause and osteoporosis are prevalent, fear of MHT induced by outdated warnings has left millions of symptomatic women untreated. The FDA’s evidence-based decision should encourage regional societies to update guidelines and reassure clinicians and patients that appropriately timed, individualized MHT is safe and effective. In Pakistan, practical and feasible steps include convening the Society of Obstetricians and Gynecologists of Pakistan (SOGP) and health authorities to form an expert panel for reviewing WHI reanalysis global guidelines; advocating to the Drug Regulatory Authority of Pakistan (DRAP) for updated product labeling aligned with current evidence, including removal of overly restrictive warnings; integrating menopause management training into continuing medical education (CME) programs for gynecologists and primary care physicians; launching targeted public awareness campaigns through electronic and print media, community health workers (e.g., Lady Health Workers), and outpatient clinics to educate women on symptoms, benefits of timely MHT, and shared decision-making; and encouraging affordable access by promoting generic MHT formulations and including essential MHT options in public sector procurement. These straightforward, low-cost actions can effectively bridge evidence-practice gaps and improve women’s health outcomes in resource-constrained settings. This letter to editor is in compliance with the TITAN guideline[6].
Footnotes
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Published online 27 January 2026
Ethical approval
This paper did not involve patients; therefore, no ethical approval was required for this LTE
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This study did not involve human participants, identifiable data, or images requiring informed consent.
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Author contributions
Zeeshan: Conceptualization, Project Administration, Supervision, Writing – Original Draft, Writing – Review and Editing. A.S.: Writing – Original Draft.
Conflicts of interest disclosure
None.
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This is new and not registered anywhere.
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This article was not commissioned and underwent external peer review.
Data availability statement
No data were generated for this manuscript.
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References
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Data Availability Statement
No data were generated for this manuscript.