A recent study published in the Journal of the American Medical Association has shown that Wyeth’s hormone combination therapy Prempro increases the risk of probable dementia in postmenopausal women aged 65 years or older. Further studies are needed to establish the role of estrogen therapies in the onset of Alzheimer’s disease.
The Women’s Health Initiative Memory Study enrolled 4,532 postmenopausal women free of probable dementia aged 65 years or older. Participants received either one daily tablet of 0.625mg of the conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate, or a matching placebo in a randomized, double-blind, placebo-controlled clinical trial.
The results of the study showed 66% of the 61 women diagnosed with probable dementia were those receiving estrogen plus progestin. This gives an increased risk of an additional 23 cases of dementia per 10,000 women per year. The authors concluded that estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older and, estrogen plus progestin therapy did not prevent MCI (a common precursor to AD) in these women. In addition, the results coupled with previously reported Women’s Health Initiative data suggest that the risks of estrogen plus progestin outweigh the benefits.
Alzheimer’s disease (AD), the most common form of dementia, is thought to affect 10% of adults over the age 65 years, with women at greater risk. One hypothesis is that lower levels of estrogen which is thought by some experts to be neuroprotective may increase the risks of dementia in postmenopausal women.
Numerous epidemiology studies have suggested that women on HRT are at less risk of dementia. However, the vast majority of studies have failed to separate the use of estrogen alone and estrogen plus progestin and these latest results appear to contradict earlier findings. This raises the question as to which component of the drug is responsible for increasing the risk of dementia.
The results are a further blow for Wyeth’s Prempro. The drug has already come under fire following the termination of the WHI long-term study due to increased risks of ovarian cancer, heart attack and stroke. Further investigation into the association of estrogen therapies and dementia is warranted.