In a new study, researchers analyzed the effects of seven different hormone treatments for menopausal symptoms on the risk of blood clots, stroke and heart attack. The study, which involved around one million women aged between 50 and 58, is the largest and most comprehensive study of currently prescribed hormonal substances in the world. The results show that the risks differ depending on the active substance and how the medicine is taken.

Researchers at Uppsala University analyzed the effects of seven different hormone treatments for menopausal symptoms on the risk of blood clots, stroke and heart attack.

Study lead author Therese Johansson commented, “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.”

Most women enter menopause between 50 and 60, when estrogen levels rapidly decline, increasing the risk of osteoporosis. The low levels can also contribute to symptoms such as hot flashes, mood swings and difficulty sleeping. To counteract these health effects, women may be prescribed hormone replacement therapy involving medicines containing hormones or hormone-like substances.

In the new study, the researchers looked at seven different types of currently used hormone replacement treatments, administered via tablets, hormone patches or hormone-releasing IUDs. The study is based on all prescriptions for hormone replacement therapy in Sweden from 2007 to 2020. The women were monitored for two years after starting hormone replacement therapy. The risk of blood clots and cardiovascular disease was compared between women who had and had not collected a prescription medicine for hormone replacement therapy.

According to Johansson, the results show clearly that the risks of hormone replacement therapy vary depending on the type of treatment. For example, she pointed out, the synthetic hormone tibolone (not available in the US), which mimics the effects of the body’s natural hormones, was linked to an increased risk of both heart attack and stroke, but not to an increased risk of blood clots. The risk of heart attack or stroke due to tibolone is estimated at one in a thousand women.

Combined preparations containing both estrogen and progesterone instead increase the risk of blood clots, including deep vein thrombosis, they found. Blood clots form in the veins and can break loose and travel with the circulation to the lungs, leading to pulmonary embolism. The researchers estimate that the risk of deep vein thrombosis resulting from this combined preparation is about seven per thousand women per year.

During the period of the study, 2007-2020, Johansson and her team observed an increase in the use of hormone patches by about 50 percent; but these preparations were not linked to the same higher risk. She noted that the increased use of safer alternatives, such as patches, is an important step forward in reducing the risk of cardiovascular disease among menopausal women.

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

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