Recently a widely-reported study from Denmark suggested that women who took estrogen and progestin hormone replacement therapy (HRT) for menopausal symptoms had an increased risk of developing Alzheimer’s disease and other types of dementia within 20 years. The increased risk was seen in both short-term users who started the therapy at 55 or younger, as well as in long-term users.
However, medical experts say the study is unable to draw a direct connection to dementia, and the overall benefits of HRT far outweigh the risks for many patients. In fact, in the same journal where the study was published, researchers from the Mayo Clinic and Harvard Medical School published an editorial, “A Causal Link Remains Unlikely,” emphasizing that the study didn’t provide evidence that HRT causes Alzheimer’s or other dementias. They noted that Alzheimer’s disease is twice as common in women than in men, making midlife exposures that might influence its risk in women considerable interest.
Erkan Buyuk, board-certified reproductive endocrinologist, infertility specialist and OB-GYN at RMA of New York who was not part of the study says HRT is the most effective therapy for hot flashes associated with menopause, which is why it is most commonly prescribed to menopausal women.
“However, HRT has a wide range of additional benefits,” said Dr. Buyuk. “It has also been shown to reduce cases of coronary heart disease, colorectal cancer, genitourinary infections and death from all-cause mortality.” He adds that HRT can also decrease the risk of osteoporosis, weak bones, improve sleep, skin health, eye health and improve overall quality of life.
How the study on HRT and dementia risk was conducted
Using Denmark’s national registry, the study assessed medical records of roughly 56,000 Danish women between 2000 and 2018. Of those women, 5,500 were later diagnosed with dementia or Alzheimer’s disease.
Dr. Buyuk said that there are many types of medications used for menopausal symptoms and they each have different mechanisms of action with short and long-term side effects. However, the HRT that is used in this study is the standard regimen that is most commonly used.
After controlling for a number of factors that could affect the development of dementia, such as age, sex, hypertension, thyroid disease and diabetes, the study found that women who used hormone therapy, even briefly, had a 24 percent higher rate of dementia and Alzheimer’s than the women who did not use hormones.
The study also found that when women used 12 or more years of hormone therapy, diagnosis of dementia rose to 74 percent.
And the study’s findings are similar to previous studies that identified some associations between taking HRT for menopause symptoms and dementia. In 2003, the Women’s Health Initiative found that women aged 65 and older who were on HRT had a greater risk of developing dementia than those who took a placebo.
Understanding the limitations of the study
There are multiple limitations to this study, said Atoosa Ghofranian, OB-GYN and REI fellow at RMA of NY who was not part of the study. Namely the control group only represented 1.8 percent of eligible patients in a specific, homogeneous population, which is far from representative or generalizable.
“The control (dementia) group also had significantly more individuals with lower education level, lower household income, more likely to live alone and have hypertension, diabetes and thyroid disease, all of which are risk factors for dementia,” said Dr. Ghofranian. “Women who needed to use hormonal therapy could have underlying predisposition to dementia as well. The relation of menopause to use of hormonal therapy is not clear.”
She adds that this is a retrospective study, only an association has been suggested, causation cannot be deduced. The study also only looked at people who used a certain type of HRT — an at the time widely prescribed combination of estrogen and progesterone.
“Hormone therapies have changed significantly over the years as the study showed that the outcomes were not ideal and since then there have been changes in the types of drugs (hormones) as well as the dosages,” said Flow Advisory Council member Jessica Shepherd, OB-GYN and chief medical officer at Verywell Health who was not part of the study. “Therefore, there may be differences in the side effects of today’s therapy.”
She adds that the outcomes from both groups showed that 31.9 percent of the women in the HRT group had dementia, compared to 28.9 percent of those in the control group.
Unpacking the scary headlines
This is an informative study that adds to the body of literature on HRT, however it should not dissuade women, especially those suffering from debilitating menopausal symptoms from taking HRT, said Dr. Ghofranian.
That growing body of research contains conflicting information. A 2019 observational study from Finland, as well as two other studies done in the UK and Taiwan, showed a very small increased risk for Alzheimer’s disease, especially when using combination hormones long-term. However, one observational study from 2021 looked at the medical records of nearly 380,000 women and found that the long-term use of hormone therapy had a seemingly “protective effect” against neurodegenerative diseases overall.
Hormones are essential to our overall well-being, but everyone is different, and hormones can fluctuate, leading to negative side effects and some illnesses, says Dr. Shepherd. This is where hormone therapy can come in to help counteract side effects and help with hormonal imbalances. When it comes to menopause specifically, hormone therapy can help regulate symptoms such as hot flashes, vaginal dryness and discomfort, sleep trouble and more.
And while the new findings may cause worry for some women taking HRT, the study highlights just how much we still don’t know about the effects of hormones on women’s cognitive and brain health.
‘It is important to emphasize that there are proven numerous health benefits from HRT and these risks and benefits should be weighed for each patient on an individualized level,” said Dr. Ghofranian. “HRT should always be a shared and individualized decision between a patient and their physician including a thorough discussion of risks and benefits.