Combination HRT linked to dementia in older women: findings reinforce need to limit its use to short-term tx in younger women. (Women's Health Initiative).

The new finding that estrogen plus progestin therapy is associated with an increased risk for probable dementia in older postmenopausal women reenforces the need to limit hormone replacement therapy use to shortterm relief of menopausal symptoms in younger women, experts agreed.

"Estrogen plus progestin should not be prescribed with the expectation that it will enhance cognitive performance in postmenopausal women," Sally A. Shumaker, Ph.D., and her associates concluded in a new analysis of data from the Women's Health Initiative (JAMA 2891201:2651-62, 2003).

On the other hand, the new data should not be overinterpreted either, menopause expert Dr. Wulf H. Utian cautioned in an interview.

"We have to be careful not to take every study, particularly a big study like WHI, and extrapolate it to everything. [The new data] say that if you start hormones in women over age 65, you might increase the risk of dementia. For women taking HRT around the menopausal age and for a relatively short time for symptom relief, these data probably have no impact at all," said Dr. Utian, executive director of the North American Menopause Society (NAMS). Furthermore, current evidence suggests that unopposed estrogen alone may offer protection against cognitive decline and that progestin may be responsible for the adverse outcomes in women on combination therapy he added.

In the WHI Memory Study, use of the continuous combination hormone replacement therapy for an average of 5.6 years in 2,229 women aged 65 and older (mean age 71) was associated with a doubling of the risk of developing probable dementia, compared with 2,303 women on placebo. Still, the overall absolute risk was small: 45 vs. 22/10,000 women aged 65 and older per year.

Combination therapy also did not protect against mild cognitive impairment, said Dr. Shumaker of Wake Forest University, Winston-Salem, N.C., and her associates.

In another part of that study, Stephen R. Rapp, Ph.D., also of Wake Forest, and his associates reported that the combination therapy did not improve cognitive function, compared with placebo (JAMA 289[20]:2663-72, 2003). And in a third trial that evaluated various subgroups with respect to stroke risk, ischemic stroke was increased by 44% among women on the combination therapy (JAMA 289[20]:2673-84, 2003).