HRT is used to treat hot flashes, night sweats, insomnia and mood changes due to the disappearance of sex hormones called estrogen and progesterone when women approach menopause.
CNN  — 

Hormone replacement therapy (HRT) is, for the most part, not linked with an increased risk of developing dementia, according to a large study of women in the United Kingdom.

However, the study – which published in the BMJ medical journal Wednesday – did show a slightly increased risk of developing Alzheimer’s disease, a specific form of dementia, among women who used estrogen-progestogen therapies for between five and nine years and for 10 years or longer. That translated into five and seven extra dementia cases, respectively, per 10,000 women.

“While the observational nature of the study means we can’t be sure of knowing what causes what, I think the results here can still reassure us that these hormone therapies mostly aren’t associated with increased risk of dementias,” Kevin McConway, emeritus professor of applied statistics at The Open University in the UK, told the Science Media Centre in London. He wasn’t involved in the research.

“And where there is some evidence of an increased risk, the increase isn’t very big at all,” he said.

Previous research into dementia and HRT has been inconsistent, the study noted. Lab studies and small trials have suggested a beneficial link between estrogen and age-related brain decline. However, a large trial of HRT, the Women’s Health Initiative Memory Study, found an increased risk of developing dementia among users of estrogen-progestogen treatments, but these women were all elderly. And a Finnish study that published in 2019 flagged an increased risk of developing Alzheimer’s disease among users of both estrogen-only and estrogen-progestogen treatments.

Using UK medical records, the researchers involved in the new study identified 118,501 women age 55 and over who were diagnosed with dementia between 1998 and 2020. A control group consisted of 497,416 women matched by age and by the same medical practice, who had no records for dementia.

Of the women with a dementia diagnosis, they found that 16,291 – 14% – had used HRT. The same percentage of women in the control group, or 68,726 of them, also used the treatment.

Not definitive

Also known as menopausal hormone therapy, HRT is used when women experience hot flashes, night sweats, insomnia and mood changes due to the disappearance of sex hormones called estrogen and progesterone. That happens as women approach menopause, typically in their late 40s or early 50s.

According to the study, overall there were no increased risks of developing dementia associated with menopausal hormone therapy “regardless of hormone type, application, dose, or duration of treatment.”

Other risk factors, such as family history, smoking, alcohol consumption, pre-existing medical conditions and other prescribed drugs, were taken into account as part of the analysis. As an observational study, it can only show an association and is not definitive.

There are different types of HRT, and the type used depends on whether a woman has a uterus. Women who don’t have one must use estrogen-only HRT. Those who haven’t had a hysterectomy must use a combination of estrogen and progesterone to avoid thickening of the lining of the womb. Recently, replacements for progesterone have broadened choices for women.

Study author Yana Vinogradova, a senior research fellow at the department of primary care at the University of Nottingham, said the new research found only a small risk association between using combined HRT for long periods and development of Alzheimer’s.

“Alzheimer’s disease is a type of dementia which develops slowly, and some signs of it such as insomnia or memory loss are similar to menopausal symptoms,” she said via email.

“The increased risk is very small and we also do not (and could not) claim that it was caused by MHT/HRT. It should not alarm users of MHT/HRT.”

The study put the risk of dementia in context for doctors and their patients, wrote Pauline Maki, a professor in the University of Illinois at Chicago’s department of psychiatry, psychology, and obstetrics & gynecology, and JoAnn Manson, a professor of medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, in an editorial that accompanied the study.

“The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they wrote. Vasomotor symptoms include hot flashes and night sweats.

Dr Haitham Hamoda, spokesperson for the Royal College of Obstetricians and Gynaecologists, and chair of the British Menopause Society, told the UK’s Science Media Centre that the findings “should be considered in the context of overall benefits and risk associated with HRT including symptom management and improvement in quality of life as well the bone and cardiovascular benefits associated with HRT intake.

“Every woman experiences the menopause differently. Symptoms can vary and be extremely debilitating, significantly impacting on their physical and psychological health, career, social life and relationships. Sadly, many women are still suffering in silence and are reluctant to seek advice and support due to concerns around HRT,” Hamoda said to the Science Media Centre.

Not the last word

While McConway said the study was “very reassuring,” he said it was unlikely to be the last word on a medical therapy that has been enveloped in mixed messages since doctors began being prescribing it widely in the late 1980s.

For years, physicians believed that giving women HRT at menopause was beneficial for the aging brain and would help prevent heart disease. But then came shocking preliminary results from the US Women’s Health Initiative, a long-term and wide-ranging national study designed to look at ways to prevent heart disease, osteoporosis, and breast and colon cancer in women.

Those 2002 and 2004 results found that the estrogen-progesterone combo of HRT actually increased the risk for heart disease, as well as stroke, blood clots, dementia and breast cancer.

The use of HRT plummeted. A decade later, other data suggested that the news wasn’t all bad, and that the risk of HRT might vary depending on a woman’s age. The original Women’s Health Initiative analysis looked at older women, who were already at risk for heart attacks, blood clots and stroke, meaning the findings might not apply to younger women.

Today, it’s believed that HRT could be helpful in controlling menopausal symptoms at the time when most women begin to go through it – in their late 40s and early 50s – when their risk for chronic disease is lower.

Women who wish to take hormones later in life, when the risk for blood clots, stroke and cancer are higher, should discuss the options thoroughly with their doctor.

CNN’s Sandee La Motte contributed to this report