Risk of thrombosis in women prescribed Hormone Replacement Therapy


Risk of thrombosis in women prescribed Hormone Replacement Therapy

What is the aim of the study and why is it important?

Hormone replacement therapy (HRT) is used to relieve adverse symptoms and reduce risk of chronic conditions in women going through menopause. There are different therapy types, which depend on the symptoms experienced by an individual.  Some women require a therapy based only on the oestrogen hormone, others may need a combination of that and another hormone, progesterone.  These therapies can also be administered differently – as tablets, patches or a cream.  Although all these treatments are effective in managing menopausal symptoms, they have a rare, but serious side effect – an increased risk of blood clots.  A recently issued guideline from the National Institute for Health and Care Excellence (NICE) stressed that research results from studies trying to estimate risk of developing blood clots as a result of HRT are still not clear, and that the findings are not a good basis for decision-making by doctors or patients.  The study therefore compared risks from all types of HRT used in the UK.

How is the research being done?

This study, for a 26 year period from 1990 to 2016, investigates real-life use of, effectiveness of and risks from all types of hormone therapy.  We use two large databases containing records from over 1700 English general practices and their associated hospital patient records.  We compare the treatment prescription records of all women who developed blood clots with those for women who did not.  We take into account other health conditions and patient characteristics which might affect the risk of blood clots to ensure that our results properly demonstrate the effects of the different therapies.

Chief Investigator

Julia Hippisley-Cox

Location of research

University of Nottingham and the University of Oxford

Date on which research approved


Project reference ID


Are all data accessed are in anonymised form?


Brief summary of the dataset to be released (including any sensitive data)

GP data for women aged 40-79 years registered between 01/01/1998 and 31/01/2017 who had a thrombosis diagnosed in the study period. Variables include risk factors for thrombosis and prescriptions for HRT. Linked mortality and hospital data for diagnosis of thrombosis.

What were the main findings?

Women who developed blood clots were more likely to be using hormonal treatments than women who did not. The risk of developing blood clots, however, was increased only for treatments using tablets and was slightly higher for higher dosages. Risk for patches, gels or creams was not increased and it was consistent for different dosages. For tablet treatments, the risk was found to differ for two types of oestrogens. Both for one hormone and combined hormone treatments, risk of blood clots was higher for the oestrogen manufactured from horse urine and lower for synthetic oestradiol.

Implications and Impact

These findings provide much clearer, more detailed information for doctors and patients about the relative risks of venous thromboembolism for all HRT treatments, and should help them to make good treatment choices. The information will also be useful to people developing best-practice guidelines.

Funding Source

Not externally funded

Research Team

Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox: University of Nottingham


  • Protocol to assess risk of venous thromboembolism associated with the use of hormone replacement therapy in real world settings: two nested case-control studies in primary care
    Authors: Vinogradova Y, Coupland CA, Hippisley-Cox J
    Ref: University of Nottingham ePrint
  • Use of hormone replacement therapy and risk of venous thromboembolism: nested case control studies using the QResearch and CPRD databases.
    Authors: Vinogradova Y, Coupland CA, Hippisley-Cox J.
    Ref: BMJ 2019; 364;k4810

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