Hormone replacement therapy and risk of venous blood clots

By Vania Morelli
Researcher at TREC

Hormone replacement therapy is a treatment used to relieve symptoms related to the menopause. Former studies have shown that hormone replacement therapy is associated with risk of venous blood clots; however, the risk may vary depending on the type of hormone replacement therapy used. A study recently published from the United Kingdom provides a more detailed picture of the blood clot risk for different hormone replacement therapy preparations. According to the authors, the study results can help clinicians and women make treatment choices.

Hormone replacement therapy is used to prevent a range of symptoms experienced by many women during menopause, such as hot flushes, night sweats, vaginal dryness, and weakening of the bones (osteoporosis). Hormone replacement therapy consists of female hormones known as oestrogen and progestogen. It is available in a variety of formulations and doses that can be prescribed in the form of tablets, skin patches, gels and creams. Along with the benefits, there are potential risks associated with using hormone therapy. Vinogradova and colleagues set out to assess in detail the association between risk of venous blood clots and all available types of hormone replacement therapy in the United Kingdom from 1998 to 2017.

In this large study, researchers used two primary care databases from the United Kingdom to compare hormone replacement therapy prescription records of over 80 000 women aged 40-79 who developed venous blood clots (cases) with those of over 390 000 women who did not (controls). Authors considered several relevant factors in their analyses that might have influenced the doctor’s decision to prescribe a specific type of hormone replacement therapy, such as lifestyle, family history of blood clots, and underlying conditions linked to blood clots. The study revealed that most oral preparations (tablets) were associated with increased risk of venous blood clots. On the other hand, no increased risk of venous blood clots was found for transdermal preparations (that is, those medications applied through the skin), including skin patches and subcutaneous or gel preparations. The authors concluded that differently from the tablets, transdermal preparations of hormone replacement therapy were not associated with risk of venous blood clots. As in all observational studies, like the one conducted by Vinogradova and colleagues, there might be still unknown or unmeasured factors that could have influenced the results on the association between hormone replacement therapy and blood clots. Therefore, caution when interpreting the results is advisable.

Finally, when addressing the possible clinical implications of the study findings, the team of researchers suggest that women with menopausal symptoms and their doctors could give greater consideration to transdermal hormone replacement therapy when making treatment choices, as this type of hormone therapy was not associated with increased risk of venous blood clots.

Reference: Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019; 364:k4810.

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