Contemporary menopausal hormone therapy and thrombotic disease: nationwide nested case-control study
Authors' conclusion
Compared with no current use of any hormone therapy, oral menopausal hormone therapy was associated with increased venous thromboembolic risk regardless of dosage and treatment duration, while prolonged use of high dose oral oestradiol (>1 mg/day) showed elevated risks of ischaemic stroke and myocardial infarction. No increased thrombotic risks were observed with transdermal therapy.
Study context
- Population
- Women aged 50–69 years living in Denmark 2003–2021 without history of venous or arterial thrombosis, cancer, liver disease, thrombophilia, oophorectomy, infertility treatment, endometriosis or polyendocrine metabolic ovarian syndrome (PMOS); national Danish health registriescases matched to controls
- Comparison
- Current use of MHT vs no current use
- Outcome
- First time diagnosis of VTE, ischaemic stroke or MI
Methodological detailsnationwide, matched by birth year
- Nationwide
- Matched by birth year
Main finding
As reported in the abstract
VTE, ischaemic stroke and MI with oral oestrogen therapy
Each group vs no current useEstimate (95% CI)
Oral oestrogen therapy
HR (VTE) 1.6(1.5–1.8)
Oral oestrogen therapy
HR (ischaemic stroke) 1.3(1.2–1.4)
Oral oestrogen therapy
HR (MI) 1.2(1.1–1.3)
Each group vs no current useEstimate (95% CI)
Oral oestrogen therapy
Absolute risk increase per year (VTE) 0.09%(0.08–0.13%)
Oral oestrogen therapy
Absolute risk increase per year (ischaemic stroke) 0.06%(0.04–0.08%)
Oral oestrogen therapy
Absolute risk increase per year (MI) 0.03%(0.01–0.04%)
- Oral oestrogen therapy
- NNH for one year of use (VTE) 1055 (95% CI 791–1266)
- Oral oestrogen therapy
- NNH for one year of use (ischaemic stroke) 1642 (95% CI 1232–2463)
- Oral oestrogen therapy
- NNH for one year of use (MI) 3846 (95% CI 2564–7692)
Observational data: associations, not effects.
Further findings
| Outcome | Estimate | |
|---|---|---|
| Oral oestradiol >1 mg/day for >5 years · >5 years of useOral oestradiol >1 mg/dayvs No current use | HR (ischaemic stroke) 1.8 (95% CI 1.4–2.2) | |
| Oral oestradiol >1 mg/day for >5 years · >5 years of useOral oestradiol >1 mg/dayvs No current use | HR (MI) 1.8 (95% CI 1.4–2.4) | |
| Transdermal therapyTransdermal combined cyclic therapyvs No current use | HR (MI) 2.1 (95% CI 1.1–4.1) | |
| 0.20.5125Ratio (log scale) |
Incidence rates among women who had not used MHT
- VTE per 10 000 person years
- 15.8
- Ischaemic stroke per 10 000 person years
- 20.3
- MI per 10 000 person years
- 13.0
Oral oestradiol >1 mg/day for >5 years · >5 years of use
- Oral oestradiol consistently associated with increased VTE risk vs no current use; risks of stroke and MI increased with treatment duration
Transdermal therapy
- Transdermal therapy not associated with increased thrombotic rates vs no current use, except MI with transdermal combined cyclic therapy
Original publication
Contemporary menopausal hormone therapy and thrombotic disease: nationwide nested case-control study. BMJ. Published 23 September 2026. doi:10.
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