The impact of long-term hormone therapy on Alzheimer's disease

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What does the data tell us about the effect of hormone therapy on the incidence of Alzheimer’s disease? Conflicting data has appeared in the literature for many years.

The WHI (Women’s Health Initiative) data demonstrated that women over 65 who were given oral Premarin and medroxyprogesterone acetate had cognitive decline, while the younger women did not. Perhaps, similar to cardiovascular disease, timing is important.

Data from a Finnish study which followed women for 25 years had different findings. Of the 8000 women who were followed, 227 eventually developed Alzheimer’s disease, with a mean age of 72. The analysis controlled for the following risk factors: age, alcohol use, smoking, exercise, occupation, and parity ( the number of children a women has had). The data demonstrated that if hormone therapy was taken for 5 years, there was no increased risk of developing Alzheimer’s.  If hormones were taken 5-10 years, the risk ration was .89, or an 11% decrease in the incidence of Alzheimer’s, although this did not reach statistical significance.
What was significant was that women who took hormones for more than 10 years had an almost 50% reduction in Alzheimer’s disease.

Three other large randomized trials in which women took HRT for less than 7 years did not demonstrate a change in cognitive function. In contrast, the Cache County study from Utah did demonstrate a significant reduction in Alzheimer’s disease if HRT was started early in menopause and continued for at least 10 years.

Mortality date from the WHI calculated 18 years after the study was completed demonstrated a decreased risk of dementia in estrogen and progesterone uses, with a larger decrease in risk in those women who took estrogen alone.

Since the WHI, there have been changes in hormone prescribing, with more use of transdermal preparations and bio-identical progesterone. It is possible that these preparations would
provide improved results.

At this point, the North American Menopause Society does not recommend that HRT be given for the prevention of dementia until more definitive data is available. Hormones given soon after surgical menopause may improve cognitive function, and should be considered at least until the age of natural menopause.

It is not likely that long-term randomized clinical trials will be done to put this issue to rest.
What can be concluded from the data as provided  is that hormone therapy started soon after menopause and continued for ten years or more may reduce the incidence of Alzheimer’s disease.

References:


Update Menopause. OBG Management, Volume 30, Number 6, June 2018
What’s the impact of long-term use of systemic hormone therapy on Alzheimer disease risk?
Andrew Kaunitz, MD, JoAnn Pinkerton, MD, JoAnn Manson, MD


Imtiaz, et al., Post-menopausal hormone therapy and Alzheimer’s disease: a prospective cohort study, Neurology, 2017; 88 (11) pp 1062-1068