Cardiovascular disease remains the leading cause of death worldwide, accounting for nearly 30% of all fatalities. Women typically experience cardiovascular disease several years later than men, with a significant rise during midlife, which coincides with the menopausal transition.
This transition is marked by a decrease in oestrogen levels and a rise in follicle stimulating hormone concentrations. These hormonal shifts can affect the neuroendocrine system, leading to symptoms such as hot flushes, night sweats, sleep disturbances, anxiety, and memory issues.
Most women experience menopause between the ages of 50 and 60, at which point estrogen levels plummet, raising the risk of osteoporosis and other health concerns, including mood swings and sleep problems. To combat these symptoms and improve quality of life, many women are prescribed hormone replacement therapy (HRT), which involves medications containing hormones or hormone-like substances.
Since its introduction in the 1970s, HRT has become a vital option for many women, with hundreds of thousands currently using it in Sweden alone. Initially, there was only one type of hormone replacement therapy; however, when a significant study in the 1990s indicated an increased risk of cardiovascular disease, its usage declined sharply.
Since then, new formulations have been introduced, leading to a notable rise in the adoption of hormone replacement therapy in relation to menopause over the past few years.
“There is concern among women that menopausal hormone therapy increases the risk of cardiovascular disease. This concern is based on older studies conducted more than 20 years ago that only looked at one type of treatment. Since then, many new preparations have been introduced, and our study shows that the previous conclusions do not apply to all types of treatments,” says Therese Johansson, postdoctoral researcher and lead author of the study, which was part of her thesis at Uppsala University.
In a recent study, Uppsala University researchers examined seven different types of hormone replacement treatments currently available, delivered through tablets, hormone patches, or hormone-releasing IUDs. This expansive analysis covered all HRT prescriptions in Sweden from 2007 to 2020 and monitored nearly one million women aged 50 to 58 for two years following their HRT initiation.
The study compared the risk of blood clots and cardiovascular disease between women who received a prescription for hormone replacement therapy and those who did not.
The findings clearly demonstrate that the risks associated with hormone replacement therapy are not uniform and depend significantly on the specific treatment utilized. Take, for instance, the synthetic hormone tibolone, which replicates the effects of natural hormones in the body. This treatment has been associated with an elevated risk of heart attack and stroke while not showing a significant increase in the risk of blood clots.
The estimated risk of experiencing a heart attack or stroke due to tibolone is approximately one in a thousand women. On the other hand, combined formulations that include both estrogen and progesterone elevate the risk of developing blood clots, such as deep vein thrombosis.
Blood clots can occur in the veins and may dislodge, traveling through the bloodstream to the lungs, which can result in a pulmonary embolism. Researchers estimate that the annual risk of deep vein thrombosis linked to this combined preparation is around seven per thousand women.
“It is important that both doctors and women are aware of the risks of menopausal hormone therapy and, in particular, that the existing drugs carry different risks of blood clots and cardiovascular disease. Tibolone, in particular, was associated with an increased risk of stroke and heart attack. Tibolone is used in Europe but is not approved in countries such as the United States. We hope that our study will lead to the drug being withdrawn from use here as well,” says Åsa Johansson, research group leader at Uppsala University and SciLifeLab and the study’s senior author.
Between 2007 and 2020, there was a noticeable rise of around 50 percent in the utilization of hormone patches, which were not associated with the same elevated risks. The growing preference for safer options like patches represents a significant advancement in lowering the risk of cardiovascular disease in menopausal women.
“The next step in our research will be to develop strategies to identify which women are at increased risk of certain diseases in connection with using hormonal drugs. In this way, we can guide patients to the most appropriate medicine for each individual and drastically reduce the number of side effects,” Åsa Johansson says.
Journal reference:
- Therese Johansson, et al. Contemporary menopausal hormone therapy and risk of cardiovascular disease: Swedish nationwide register based emulated target trial. BMJ, 2024; DOI: 10.1136/bmj-2023-078784