Risk of dementia linked to menopausal hormone therapy, even in women aged 55 and under

Menopausal hormone therapy was linked to dementia and Alzheimer’s disease, even in women who received treatment at age 55 or younger, a large observational study in Denmark has suggested.

Women aged 50-60 who had received estrogen-progestogen therapy had an increased risk of dementia from all causes (HR 1.24, 95% CI 1.17-1.33) compared to women who did not. had never used the treatment, reported Nelsan Pourhadi, MD, of the University of Copenhagen Hospital in Denmark, and co-authors.

Hazard ratios increased with longer durations of use, from 1.21 (95% CI 1.09-1.35) for 1 year or less to 1.74 (95% CI 1.45 -2.10) for more than 12 years, the researchers wrote in The BMJ.

Associations persisted in women who received treatment at age 55 and younger (HR 1.24, 95% CI 1.11-1.40), or when restricted to late-onset dementia (HR 1.21, 95% CI 1.12-1.30) or Alzheimer’s disease (HR 1.22, 95% CI 1.07-1.39).

What the results mean is unclear. “Further studies are warranted to determine whether these findings represent a real effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women needing these treatments,” Pourhadi wrote. and his colleagues.

Kejal Kantarci, MD, of the Mayo Clinic in Rochester, Minnesota, co-author of a accompanying editorialagreed.

“A relationship between hormone therapy and dementia does not mean that menopausal hormone therapy causes dementia,” Kantarci said. MedPage today. “While that could be one reason, there are many other factors that can contribute to this relationship.”

“For example, women who seek hormone therapy for reasons such as cognitive difficulties, sleep disturbances, or vasomotor symptoms may already be prone to dementia later in life,” Kantarci continued.

“Clinical trials provide the strongest evidence of causation,” she stressed. “Recent clinical trials indicate that women receiving hormone therapies during the menopausal transition are not at risk of cognitive decline.”

Although the analysis does not prove a causal link, “the possibility of a causal link is increased by the new finding (since better records were available) that the longer people took this type of HRT [hormone replacement therapy]the more likely they were to develop dementia,” observed Gill Livingston, PhD, of University College London in England.

“Furthermore, the prescription of HRT predated the dementia by many years,” Livingston wrote on the UK’s Science Media Center. “In addition, the researchers took other risk factors for dementia into account in the analysis.”

THE North American Menopause Society (NAMS) states that the benefit-risk ratio of hormone therapy is favorable for treating vasomotor symptoms and preventing bone loss in women 60 years of age and younger, or those within 10 years of the onset of menopause and which have no contraindications. For women over 60 or those starting hormone therapy more than 10 years after the onset of menopause, NAMS indicates that the benefit/risk ratio may be less favorable due to risks of coronary heart disease, stroke brain, venous thromboembolism or dementia.

Pourhadi and colleagues used data from the national register to identify 5,589 dementia cases and 55,890 age-matched controls without dementia between 2000 and 2018 among a population of all Danish women aged 50 to 60 in 2000 without history of dementia and no underlying reason preventing them from using menopausal hormone therapy.

Women in the case group more often had shorter education, lower family income, hypertension, diabetes, and thyroid disease than controls.

Dementia was diagnosed at an average age of 70. Before diagnosis, 1,782 (32%) cases and 16,154 (29%) controls received estrogen-progestogen therapy from an average age of 53 years. The average duration of use was 3.8 years for cases and 3.6 years. for controls.

Continuous (HR 1.31, 95% CI 1.18-1.46) and cyclic (HR 1.24, 95% 1.13-1.35) treatment regimens were associated with later diagnosis of dementia. Progestogen-only therapy and vaginal estrogen-only therapy were not associated with dementia.

The findings cannot inform shared decision-making about hormone therapy for menopausal symptoms, Kantarci and JoAnn Manson, MD, DrPH, of Harvard Medical School in Boston, said in their editorial.

“Confounding factors could produce a false signal indicating a higher risk of dementia in young women using hormone therapy for a short or long duration,” Kantarci and Manson wrote. “In particular, an increased risk of dementia with less than a year of hormone treatment is not biologically plausible, further confirming the presence of confounding factors.”

Brain imaging biomarkers can help determine whether hormone treatment affects the pathophysiology of dementia at an early stage, “making it possible to assess its influence on dementia risk in trials of recently postmenopausal women” , they added.