On September 23, 2026, The BMJ published a nationwide Danish nested case-control study (Berggreen et al., DOI 10.1136/bmj-2026-100688). It found that current use of any oral menopausal hormone therapy was linked to a higher risk of venous thromboembolism (blood clots in the legs or lungs) regardless of dose or how long it was taken. Transdermal therapy delivered through patches, gels or sprays showed no general increase in thrombotic risk regardless of regimen, active ingredient, dose or duration. Stroke and heart attack risk rose only with high-dose oral estradiol, above 1 mg a day, taken for more than a year, and it climbed with longer use.

Why It Matters

This lands in a market already moving fast. Afterglow reported on September 5 that US estradiol patch prescriptions nearly tripled after the FDA removed the black-box warning, from about 594,000 in June 2024 to 1.6 million in May 2026, and that the FDA was working to raise patch supply while declining to call it a shortage. A large, clean dataset saying the delivery route drives clot risk, with a clear preference for transdermal, pushes demand further toward exactly the formulation that is already hard to get. Expect it to feature in the next round of pressure on manufacturers and the FDA's shortage list. For menopause telehealth platforms, many of them cash-pay and scaling on the hormone-therapy boom, the study is a formulary and liability signal. Defaulting to oral estradiol because it is cheaper or easier to ship now carries a documented, if small, risk difference that a prescriber has to justify. It also helps the growing field of transdermal and local delivery products (gels, sprays, vaginal estrogen for genitourinary symptoms) that sits closest to sexual wellness. The absolute numbers are reassuring for most healthy women in their 50s. The comparative numbers are the part that changes practice.

The scale is what makes it land. The researchers used Danish registries for women aged 50 to 69 between 2003 and 2021, with no history of blood clots, cancer, liver disease, endometriosis, PCOS, fertility treatment or oophorectomy. They identified 9,807 women with a first venous thromboembolism, 18,460 with ischaemic stroke and 11,974 with heart attack, matched by birth year to 49,035, 92,300 and 59,870 controls respectively. Among women not using hormone therapy, rates were 15.8, 20.3 and 13.0 per 10,000 person-years. Oral oestrogen, alone or with a progestin, added absolute yearly risks of 0.09% for VTE, 0.06% for stroke and 0.03% for heart attack. That works out to one extra clot per 1,055 women on oral therapy for a year, one extra stroke per 1,642 and one extra heart attack per 3,846. The one transdermal exception was a higher heart-attack rate with combined transdermal cyclic therapy, which the authors say rests on sparse data.

The limits are standard for this design. It is observational and cannot establish cause. The registries lacked age at menopause, BMI and smoking status, and the population may not reflect more ethnically diverse groups. In a linked BMJ opinion piece, Dr. Amani Meaidi of Copenhagen University Hospital – North Zealand told Healio (as reported by Medical Daily) that menopausal hormone therapy "should not be viewed as one uniform treatment." She said transdermal delivery is preferred on these findings, and that when pills are used, clinicians should aim for the lowest effective dose, ideally no more than 1 mg of estradiol daily, and reassess regularly.

Sources

Update — 2026-09-29

Initial entry — story first created.