Certain hormone replacement therapy (HRT) tablets containing both oestrogen and progestogen are associated with a higher risk of heart disease, according to a new study published in the British Medical Journal.
HRT is used to relieve menopausal symptoms such as hot flushes and night sweats, and different treatments are available depending on symptoms.
Some previous trials have suggested a link between menopausal hormone therapy and an increased risk of cardiovascular disease, but information on risks linked to different types of therapy during menopause is lacking, the researchers said.
The Swedish researchers used data from 138 emulated trials, which are observational studies that mimic clinical trials, involving 919,614 healthy women in Sweden aged 50-58 between 2007 and 2020 who had not used hormone therapy in the previous two years.
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They excluded women with a history of heart disease, stroke, narrowed arteries or cancer, and who had undergone surgery to remove their ovaries, a hysterectomy, or sterilisation.
Using monthly prescription records the women were assigned to one of eight menopausal hormone treatment types. Hospital records were then used to track cardiovascular events over two years, and other potentially influential factors such as age, education level, region of residence, high blood pressure and diabetes were taken into account.
During this monitoring period 24,089 cardiovascular events were recorded.
Compared with not starting menopausal hormone therapy, using oral combined continuous therapy was associated with an increased risk of ischemic heart disease. No increased risk of cardiovascular disease was found for transdermal treatments, which include skin patches, gels and creams.
An increased risk of blood clots was also found for oral combined continuous, oral combined sequential, oral unopposed oestrogen, and transdermal combined therapy.
Another HRT tablet called tibolone was associated with an increased risk of heart disease, heart attack and stroke, but not blood clots.
The British Medical Journal notes that these are observational findings, meaning “no firm conclusions can be drawn about causality”, and the authors point to limitations including a lack of data on menopausal status and the possibility that other unmeasured factors, such as smoking and body mass index, may have affected their results.
However, the journal added that by using an emulated target trial design they reduced the bias common to observational studies and the use of registry data allowed them to distinguish between different types of hormone therapies, including differences in administration, regimens and combinations of hormones.
The authors said: “These findings highlight the diverse effects of different hormone combinations and administration methods on the risk of cardiovascular disease.”
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