Different Hormone Treatments During Menopause Carry Different Risks

Researchers at Uppsala University have investigated the effects of seven different hormone treatments for menopausal symptoms on the risk of blood clots, stroke and heart attack. The study, in which around one million women aged between 50 and 58 participated, shows that the risks vary depending on the active ingredient and how the medication is taken. Published in the journal BMJ, the study is the largest and most comprehensive investigation of currently prescribed hormone treatments in the world.

“There is concern among women that hormone therapy during menopause increases the risk of cardiovascular disease. This fear is based on older studies conducted more than 20 years ago and only one type of treatment was studied. Since then, many new preparations have come onto the market, and our study shows that the earlier conclusions do not apply to all types of treatment,” says Therese Johansson, postdoc and lead author of the study, which was part of her doctoral thesis at Uppsala University.

Risks of Hormone Replacement Therapy Vary Depending on the Type of Treatment

Most women experience menopause between the ages of 50 and 60. Estrogen levels drop sharply, increasing the risk of osteoporosis. Low hormone levels can also cause health problems such as hot flashes, mood swings and sleep disturbances. To counteract these health effects, women may be prescribed hormone replacement therapy with drugs containing hormones or hormone-like substances.

In Sweden alone, hundreds of thousands of women are currently taking hormone replacement therapy, and this type of treatment has been available since the 1970s. Back then, there was only one type of hormone replacement therapy, and when a major study in the 1990s showed that it increased the risk of cardiovascular disease, its use declined rapidly. Since then, new preparations have come onto the market, and in recent years, the use of hormone replacement therapy for menopause has increased significantly.

In the new study, the researchers examined seven different types of currently used hormone replacement treatments, administered via tablets, hormone patches or hormone-releasing coils. The study is based on all prescriptions for hormone replacement therapies in Sweden from 2007 to 2020 and includes almost one million women aged 50 to 58. The women were followed for two years after starting hormone replacement therapy. The risk of blood clots and cardiovascular disease was compared in women who had been prescribed a hormone replacement therapy prescription and in women who had not taken such a drug. The results clearly show that the risks of hormone replacement therapy vary depending on the type of treatment.

Safer Alternatives

For example, the synthetic hormone tibolone, which mimics the action of the body’s natural hormones, has been associated with an increased risk of heart attacks and strokes, but not with an increased risk of blood clots. The risk of heart attack or stroke due to tibolone is estimated to be one in a thousand women. Combined preparations containing both estrogen and progesterone instead increase the risk of blood clots, including deep vein thrombosis. Blood clots form in the veins and can come loose and travel with the bloodstream to the lungs, causing a pulmonary embolism. Researchers estimate that the risk of deep vein thrombosis from this combination preparation is about seven in every thousand women per year.

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 for blood clots and cardiovascular disease. Tibolone in particular has been 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. The researchers hope that their 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 senior author of the study.

During the study period from 2007 to 2020, an increase in the use of hormone patches of about 50 percent was observed, and these preparations were not associated with the same increased risk. The increasing use of safer alternatives such as patches is an important step forward in reducing the risk of cardiovascular disease in menopausal women. The next step will be to develop strategies to identify which women are at increased risk of certain diseases in the context of taking hormonal medications.