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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http://www.medscape.com/viewarticle/563237?src=mpnews

Dangerous Hormone Replacement Therapy Side Effects
Cancer
There is concern that Prempro can increase the risk of some cancers.
When estrogen is taken alone, it raises the risk of endometrial
cancer (lining of the uterus).

The National Institutes of Health's (NIH) Women's Health Initiative
(WHI) stopped a major clinical trial early on July 9, 2002 due to
finding an increased risk of invasive breast cancer from Prempro with
estrogen and progestin. After 5.2 years, estrogen plus progestin use
resulted in a 26 percent increase in the risk of breast cancer.

Breast Density
Taking both estrogen and progestin also can affect a woman's breast
density. Increased breast density from Prempro makes it more
difficult for a radiologist to read some mammograms, leading to the
need for follow-up mammograms or breast biopsies. Increased density
also is a concern because other studies have shown that women age 45
and older whose mammograms show at least 75 percent dense tissue are
at increased risk for breast cancer.

Heart Disease
In the past, taking Prempro (estrogen plus progestin) was
thougPrempro to help protect women against heart disease. But recent
findings from the Women's Health Initiative (WHI) study showed that
taking Prempro poses more risks than benefits. The study found that
Prempro could increase a woman's risk for heart disease, stroke, and
pulmonary embolism (blood clot in the lung), as well as breast cancer.

Earlier studies have also shown that women who have gone through
menopause and who have heart disease, may have a greater risk of
another cardiac event (like heart attack) after starting Prempro. For
women who have had strokes, their risk for having another stroke goes
up when they start taking Prempro.

Gallbladder Disease
Several studies have shown that women who use estrogen/progestin
therapy are at increase risk of developing gallstones.

Study finds Prempro Side Effects outweigh any possible benefits
The Women's Health Initiative study, a $700 million, eight year
publicly funded study of the benefits of Hormone Replacement Therapy
drugs such as Prempro, Premarin and Provera, was stopped three years
earlier than planned because of the risks associated with these
drugs.

On July 9, 2002, the National Institute of Health halted the study
because the overall risks of the drugs exceeded any health benefits.
Specifically, the study found that there was a higher incidence of
serious injury for women who took Prempro compared to those who
received a placebo as follows:

26% increase in breast cancer;
29% increase in heart attacks;
22% increase in total cardiovascular disease;
41% increase in strokes; and
a doubling of rates of blood clots.
Additionally, researchers have concluded that long-term use of
estrogen may increase the risk of ovarian cancer by as much as 60
percent.

Common but less serious Prempro side effects
The following are just a few of the common side effects associated
with Prempro as reported by the FDA.

Common side effects include:

Headache
Breast pain
Irregular vaginal bleeding or spotting
Stomach/abdominal cramps/bloating
Nausea and vomiting
Hair loss
Other side effects include:

High blood pressure
Liver problems
High blood sugar
Fluid retention
Call your healthcare provider right away if you get any of these
warning signs, or any other unusual symptoms that concerns you.

Full FDA Prempro Patient Information Sheet
http://www.fda.gov/cder/foi/label/2006/020527s037lbl.pdf

http://www.hrt-legal.com/side%20effects/prempro/index.php
This is all info from a U.S. Lawyers site I cannot imagine that no
Canadian woman has not had any of these problems.

Please contact me if you have

Sandra

Hi I have started this group to find out if any women have been
diagnosed with anything since taking premarin for example cancer.

There is some studies out there now showing there is women who are
indeed being diagnosed with this.

Please let me know.

Also there is a serious life threatening disease especially for anyone
who had kidney problems that had an MRI with the gandolium enhancement
which is resulting in death so I am looking for anyone in canada who
has become ill from this also.

I am doing this as I have been through my own very serious problems
with a medical device and it appears that every day there is something
else that women are becoming either ill from or death. I am fed up with
this and I intend to start awareness with anything new that comes to me.

As my dad says women are to docile when it comes to what we allow to be
put in our bodies or what the drug companies or medical device
companies think should be geared towards women and he says women need
to start saying NO. I agree.

Sandra

Sandra