WebMDNews

News Author: Caroline Cassels
CME Author: Penny Murata, MD
Release Date: September 24, 2007

September 24, 2007 — New research suggests that hormone therapy (HT) does not improve memory in recently postmenopausal women with cognitive complaints.
In the largest study to date to examine the effects of HT in early postmenopausal women, the Cognitive Complaints in Early Menopause Trial (COGENT) found HT had no impact on verbal memory vs placebo.

“These results are similar to previous studies suggesting hormone therapy has minimal effect on a woman’s memory when taken many years after menopause,” said lead author Pauline Maki, PhD, from the University of Illinois at Chicago, in a statement from the American Academy of Neurology.
The study is published in the September 25 issue of Neurology.

Increased Sexual Interest
However, although no impact on cognition was found, investigators did observe that women taking HT experienced an increased level of sexual interest and thoughts.

“The level of sexual interest reported by women on hormone therapy increased 44% and their number of sexual thoughts increased 32% compared to the placebo group,” said Dr. Maki. In addition, women taking HT who had vasomotor symptoms showed a decrease in such symptoms and an improvement in general quality of life (QoL).

In the Study of Women’s Health Across the Nation, which included 16,065 participants, 42% of perimenopausal women and 40% of postmenopausal women complain of forgetfulness vs 30% of their premenopausal counterparts.

According to the COGENT authors, at least 6 randomized trials have reported positive effects of estrogen therapy on cognitive function in recently menopausal subjects, but these trials were limited by small sample size and typically included symptomatic women. Larger trials of combined estrogen and progestin HT and cognitive function in women older than 65 years have shown either negative or neutral effects.

The aim of COGENT was to examine the effects of HT on verbal memory, attention, and subjective memory in a large, randomized, multicenter, placebo-controlled

 trial. Secondary outcomes included the impact of HT on sleep, perceptions of sexuality, and QoL.
The study had a target enrollment of 275 healthy postmenopausal women with intact uteri whose last natural menstrual cycle had ended between 1 and 3 years before entry into the study.

Study Enrollment Fell Short

Study recruitment began in March 2002 but was terminated before it reached the target sample size. This was because of a drop in participation regarding safety concerns raised by results from the Women’s Health Initiative (WHI), which suggested that long-term use of HT increased the risk for breast cancer and did not protect against cardiovascular disease.

The study sample included 180 women between the ages of 45 and 55 years, all of whom underwent baseline testing of memory, attention, and subjective cognition. They were then randomized to receive daily HT consisting of 0.625 mg conjugated equine estrogen and 2.5 mg medroxyprogesterone acetate or placebo during a 4-month period. The final analysis included 158 women who completed the 4-month trial.

For primary efficacy endpoints, the researchers found no differences between the 2 treatment groups. However, they did find negative effects on short-term and long-term verbal memory that approached significance but were small in magnitude.
“While our results are inconsistent with smaller studies that found improvement in verbal memory for women who only used estrogen, it may be that progesterone modifies the protective effects of estrogen on verbal memory,” said Dr. Maki.

The study also showed a reduction in vasomotor symptoms, including hot flushes (also known as hot flashes) and night sweats, among subjects in the HT group and a general improvement in QoL outcomes vs placebo.

“COGENT is limited by lower power due to decreased enrollment following publication of the WHI results, though it is the largest study to date examining the effects of HT on cognitive function in recently menopausal women. The results are similar to previous studies suggesting minimal effects across cognitive domains,” the study authors write.
Wyeth Pharmaceuticals funded this study. The authors have disclosed financial relationships with Wyeth and the University of California, San Francisco.
Neurology. 2007;69:1322-1330.

Clinical Context
The effect of HT on cognitive function in postmenopausal women has not been clear. In 2005, Bagger and colleagues in the January-February issue of Menopause reported that early HT in postmenopausal women was linked to a decreased risk for impaired cognitive function. In the May 2006 issue of the Journal of Clinical Endocrinology and Metabolism, Resnick and colleagues found that HT in elderly women was associated with decreased verbal learning and memory.