Copenhagen, Denmark—A new nationwide, nested, case-control study from Denmark has ignited a fierce debate after identifying a possible link between menopausal hormone therapy (MHT) and all-cause dementia and Alzheimer’s disease.

The report in The BMJ stated that the association was noted even in women who received treatment at age 55 years or younger.

A linked editorial from Kejal Kantarci, MD, of the Mayo Clinic and JoAnn E. Manson, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, argued that a causal link remains unlikely.

The Danish researchers sought to assess the association between the use of MHT and the development of dementia according to the type of hormone treatment, duration of use, and age at usage.

Using Danish national registries, they reviewed 5,589 incident cases of dementia and 55,890 age-matched controls between 2000 and 2018. The participants were from a population of all Danish women aged 50 to 60 years in 2000 with no history of dementia or contraindications for the use of MHT.

The study found that compared with women who had never used treatment, those who had received estrogen-progestin therapy had an increased rate of all-cause dementia (hazard ratio [HR] 1.24; 95% CI, 1.17-1.33). In addition, increasing durations of use yielded higher HRs, ranging from 1.21 (1.09-1.35) for 1 year or less of use to 1.74 (1.45-2.10) for more than 12 years of use.

“Estrogen-progestin therapy was positively associated with the development of dementia for both continuous (1.31 [1.18-1.46]) and cyclic (1.24 [1.13-1.35]) regimens. Associations persisted in women who received treatment at the age 55 years or younger (1.24 [1.11-1.40]),” the authors wrote. “Findings persisted when restricted to late-onset dementia (1.21 [1.12-1.30]) and Alzheimer’s disease (1.22 [1.07-1.39]).”

The study concluded that MHT was positively associated with the development of all-cause dementia and Alzheimer’s disease. However, the researchers call for further studies to determine whether these findings represent an actual effect of MHT on dementia risk or whether they reflect an underlying predisposition in women in need of these treatments.

The commentators pointed out, “Confounding factors could be producing a spurious signal for higher dementia risk in younger women using hormone therapy for either a short or long duration. In particular, increased dementia risk with less than one year of hormone treatment is not biologically plausible, further supporting the presence of confounding factors. Approximately two-thirds of women have subjective cognitive difficulties during the menopausal transition and may experience a temporary decline in cognitive processing speed. Women with subjective cognitive complaints, vasomotor symptoms, and sleep disturbances would likely seek hormone therapy more often than those who do not experience these symptoms.”

Background information in the study noted that dementia affects more women than men worldwide. “Even when controlling for differences in survival rates, the incidence of dementia among women is higher compared with that of men, suggestive of risk factors related to the female sex,” the authors wrote, pointing out that estrogen is known to have both neuroprotective and neurodamaging properties.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

 « Click here to return to Weekly News.