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BMJ. 2019 Jan 9;364:k4810. doi: 10.1136/bmj.k4810.

Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases.

Author information

1
Division of Primary Care, University of Nottingham, Nottingham NG2 7RD, UK Yana.Vinogradova@nottingham.ac.uk.
2
Division of Primary Care, University of Nottingham, Nottingham NG2 7RD, UK.

Abstract

OBJECTIVE:

To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy.

DESIGN:

Two nested case-control studies.

SETTING:

UK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data.

PARTICIPANTS:

80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391 494 female controls.

MAIN OUTCOME MEASURES:

Venous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs.

RESULTS:

Overall, 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%)and 16 938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiolhad a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01).

CONCLUSIONS:

In the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; JHC is professor of clinical epidemiology at the University of Nottingham and unpaid director of QResearch, a not-for-profit organisation which is a joint partnership between the University of Nottingham and EMIS (commercial IT supplier for 60% of general practices in the UK); JHC is also a paid director of ClinRisk, which produces open and closed source software to ensure the reliable and updatable implementation of clinical risk algorithms (including QRISK2) within clinical computer systems to help improve patient care; no other relationships or activities that could appear to have influenced the submitted work.

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