COGENT: Hormone Therapy Does Not Improve Cognition in Early
Postmenopausal Women CME
News Author: Caroline Cassels
CME Author: Penny Murata, MD
Disclosures

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.

This randomized, double-blind, placebo-controlled, multicenter, pilot
study examined the effects of HT on memory, attention, cognition,
sleep, sexuality, and QoL in recently postmenopausal women with
cognitive complaints.

Study Highlights
180 healthy postmenopausal women aged 45 to 55 years were randomized
to receive placebo or HT for 4 months.
Inclusion criteria were an intact uterus, last natural menstrual
cycle in previous 12 to 36 months (or last menstrual cycle from 6 to
< 12 months and serum levels of follicle-stimulating hormone > lower
limit of normal for postmenopausal women), English speaking, score of
10 or higher on the Primary Mental Abilities Vocabulary Test, at
least 1 cognitive complaint on the Self-reported Cognitive Function
Questionnaire of memory and concentration, and absence of disease
that would influence cognition.
Exclusion criteria were estrogen-dependent neoplasm, endometrial
hyperplasia, thrombophlebitis, thrombosis, thromboembolic disorders,
myocardial infarction, ischemic heart disease, cerebrovascular
accident, stroke, transient ischemic attack, estrogen or progestin
hypersensitivity, estrogen or progestin use in the previous 8 weeks,
more than 0.5 pack of cigarettes per day, a history of alcohol abuse,
cognitive impairment on the Mini-Mental State Examination, or
medication that could affect central nervous system function.
80 of 91 women assigned to the placebo group completed the study.
78 of 89 women assigned to receive conjugated equine estrogen 0.625
mg and medroxyprogesterone acetate 2.5 mg completed the study.
Groups appeared similar in age (mean, 52 years), height, weight,
months since last period, severity of hot flush, months of previous
use of HT, months since last use of HT, and white race.
Primary outcomes of change in memory, attention, and subjective
cognition, measured at baseline and after 4 months, were not
significantly different between the HT and control groups:

Results of the California Verbal Learning Test to assess verbal
learning and memory decreased with time but were similar for both
groups.
The Memory Function Questionnaire improved with time for frequency of
forgetting and retrospective functioning for both groups and for
seriousness of forgetting for HT group, but results were similar for
both groups.
Brief Test of Attention results improved with time for placebo group
but were similar for both groups.
Secondary outcomes were additional measures of cognitive function,
emotion, sexuality, and sleep:

The HT and control groups did not differ in results from the Benton
Visual Retention Test, Educational Testing Service Card Rotation
Test, Letter Fluency Test, Digit Span Forward and Backward Subtests
of Wechsler Memory Scale-Revised, and Positive and Negative Affect
Scale.
Of 6 subscales of the McCoy Female Sexuality Scale to assess
sexuality, level of interest and sexual thoughts increased more in
the HT vs the control group (P < .01 and P < .05).
Small increase in sleeping hours and decrease in time to fall asleep
were reported.
Post hoc analysis of women with a hot flush severity score of at
least 1.2 on baseline diary cards showed greater improvement in the
HT vs the control group for symptoms (P = .001), Utian Quality of
Life occupation index (P < .01), and total score (P < .05).
Most common adverse events occurring up to 15 days after the last
dose for the placebo vs the HT groups included headache (14 vs 10),
breast tenderness (3 vs 13), nasopharyngitis (10 vs 4), pharyngitis
(6 vs 4), sinusitis (5 vs 5), back pain (3 vs 6), abdominal pain (2
vs 6), dyspepsia (2 vs 6), toothache (5 vs 2), muscle cramps (2 vs
4), and arthralgia (1 vs 5).
3 serious adverse events were not related to treatment.
The study was terminated because of decreased enrollment short of the
expected 275 subjects.
Pearls for Practice
In recently postmenopausal women with cognitive complaints, HT does
not affect memory, attention, or cognition.
In recently postmenopausal women with cognitive complaints, HT seems
to improve sexual interest and thoughts, but not sleep or QoL.



Medscape Medical News 2007. ©2007 Medscape



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