UB Research Team Shows Estrogen Levels Affect Cognitive Abilities of Postmenopausal Women

BUFFALO, N.Y. -- Low levels of estrogen may impair some cognitive functions, while estrogen-replacement therapy may help improve certain thinking and biological brain processes, and also may play a role in elevating mood, results of studies involving postmenopausal women conducted by researchers at the University at Buffalo have shown.

A team of scientists led by Uriel Halbreich, M.D., UB professor of psychiatry and gynecology and obstetrics, and an expert in psychopharmacology, hormonal disorders and behavior, has reported that the performance of postmenopausal women on certain tests measuring the ability to integrate several cognitive functions improved significantly after a course of estrogen-replacement therapy (ERT).

Another study showed that estrogen improved serotonin activity in postmenopausal women. Decreased activity of the body chemical in the brain is associated with depression, anxiety, panic and other neuropsychiatric disorders.

Results of the research were presented at the annual meeting of the International College of Neuropsychopharmacology.

The study of cognitive functioning involved 34 postmenopausal women with an average age of 52, and 24 women of reproductive age who averaged 34 years old.

“We gave post menopausal women and women of child-bearing age a series of tests that measure a wide variety of cognitive functions,” Halbreich said. The tests measured integrative capabilities, reaction time, mental alertness, verbal abilities, coordination, dexterity and other capabilities.

“The postmenopausal women didn’t function as well as the younger group on most of the cognitive tests,” Halbreich said. “Their behavior was not abnormal, but it was very different from the younger women. Then we gave them estrogen for 60 days, and there was a significant improvement, which was correlated with the plasma levels of estrogen.”

Results showed that integrative abilities, reaction times and short-term verbal memory of postmenopausal women improved after estrogen therapy, but manual dexterity and visual memory did not.

Halbreich theorizes that estrogen may “protect” some functions that typically decline with age or menopause. Because there was no improvement on some tests, the hormone effect may be selective, influencing certain neural circuits and not others, he said.

In the study of the effect of estrogen on mood, Halbreich’s team tested 11 postmenopausal women who were candidates for ERT and 15 women of reproductive age, to determine if estrogen had an effect on serotonin, a body chemical known to serve as a central-nervous-system transmitter and to be involved in the regulation of behavior.

Halbreich said earlier research has suggested that postmenopausal women, who have low levels of estrogen, might be more susceptible to the development of depression, and that this vulnerability is thought to be associated with low serotonin response. Decreased serotonin activity has been associated with depression, obsessive-compulsive disorder, aggression, anxiety and panic disorders.

Halbreich’s team studied the hormonal response to a serotonergic agonist called m-CCP, and found it was blunted in postmenopausal women, compared to women of reproductive age. This blunted response, indicative of a decreased serotonergic activity, was “corrected” with ERT.

He also reported that increases in the levels of the hormones cortisol and prolactin were associated with the increase in plasma levels of estrogen, a further indicator that ERT boosts serotonergic activity.

Halbreich’s team also studied the effect of estrogen on the level of Alpha 2 receptors, a component of noradrenergic activity and another neurotransmitter involved in regulating mood. Receptor levels of the postmenopausal women were tested before and after 60 days of ERT.

“Persons diagnosed with depression have been found to have elevated levels of Alpha 2 receptors,” Halbreich said. “In postmenopausal women, Alpha 2 receptors are higher than in women of reproductive age. When we gave estrogen, the level of these receptors decreased. When we stopped estrogen or added progesterone, Alpha 2 receptors increased again.”

“If a decrease in some serotonin activities is involved in the pathophysiology of some mood disorders,” he said, “then our findings suggest that estrogen replacement therapy may be beneficial for preventing these disorders.” Estrogen replacement may be useful in treating depression in postmenopausal women, he said, but it is still unclear if estrogen improves the mood of women who are not clinically depressed.

Both studies were supported by grants from the National Institute of Mental Health.

The investigators, in addition to Halbreich, were Nathan Rojansky, M.D.; Steven Palter, M.D.; Henry Tworek, Ph.D.; Francis Genco, Pharm.D.; Sook-Haeng Joe, M.D.; Paul Hissin, Ph.D.; Ke Wang, M.D.; Lucille A. Lumley and Colleen Manning.