Timing of HT may affect risk for Alzheimer’s disease

Previous trials have suggested an increased risk for Alzheimer’s disease in women who use hormone therapy, but researchers from the Cache County Study have determined that this association may depend on the timing or type of hormone therapy.

“This has been an area of debate because observational studies have shown a reduced risk of Alzheimer’s disease with hormone therapy use, while a randomized controlled trial showed an increased risk. Our results suggest that there may be a critical window near menopause where hormone therapy may possibly be beneficial,” researcher Peter P. Zandi, PhD, of The Johns Hopkins University, said in a press release. “On the other hand, if started later in life, hormone therapy could be associated with an increased risk of developing Alzheimer’s disease.”

According to Zandi and colleagues, the Cache County Study (CCS) was one of the prospective, observational studies suggesting that HT could reduce the risk for Alzheimer’s disease.

The patients consisted of elderly residents of Cache County, Utah, aged at least 65 years (as of Jan. 1, 1995), who underwent dementia screening (wave 1). For those patients who did not have dementia upon baseline screening, researchers conducted follow-up in 1998-1999 (wave 2), 2002-2003 (wave 3) and 2005-2006 (wave 4).

During the 7-year follow-up, 248 patients developed incident dementia, researchers wrote. Of those, 176 patients were diagnosed with definite, probable or possible Alzheimer’s disease. According to researchers, these patients tended to be older at baseline (78.1 years), more likely to have apolipoprotein E E4 allele and a history of diabetes vs. other patients.

In classifying the 1,105 patients (62.5%) who reported a history of HT use, researchers categorized patients as “opposed,” if the patient used a medication that included progestin plus estrogen (37%), or “unopposed” if they had not (59.7%), or unknown (3.3%).

According to data, women who used any type of HT within 5 years of menopause had a 30% reduced risk for developing Alzheimer’s disease (95% CI, 0.49-0.99). This was especially the case if women used any type of HT for more than 10 years.

However, the risk for Alzheimer’s disease was not reduced in those women who began HT use 5 or more years after menopause. Moreover, for opposed patients who began treatment within 3 years after the CCS baseline, the risk for Alzheimer’s disease increased (HR=1.93%; 95% CI, 0.94-3.96), researchers wrote.

In an accompanying editorial, Victor Henderson, MD, MS, of Stanford University, and Walter A. Rocca, MD, MPH, of the Mayo Clinic in Rochester, Minn., wrote that the direction and magnitude of endogenous and exogenous estrogens effects on risk for Alzheimer’s disease in women remain controversial.

“While this well-designed study supports the possibility that short-term hormone use may reduce the risk of [Alzheimer’s disease], more research is needed before we can make new clinical recommendations for women and their use of hormone therapy,” Henderson said in a press release.

In their editorial, Henderson and Rocca wrote that a new trial that included young postmenopausal women who are randomly assigned to placebo or an estrogen and followed for up to 3 decades for incident Alzheimer’s disease could lead to convincing evidence.

For more information:

Henderson VW. Neurology. 2012;79:1840-1841.

Shao H. Neurology. 2012; 79:1846-1852.

Disclosure:The researchers report no relevant financial disclosures