Does hormone replacement therapy preserve everyday memory functioning in postmenopausal women

1
Does hormone replacement therapy preserve
everyday memory functioning in postmenopausal
women?

• Donna Spooner, Dr Nancy Pachana
• The School of Psychology, The University of
  Queensland
• Prof Soo Khoo, Dr Sheila ONeill
• The Betty Byrne Henderson Centre, The Royal
  Womens Hospital, Brisbane

2
Characteristics of the Menopause

• The menopause is the permanent cessation of
  menstruation
• Results from the loss of ovarian follicular
  activity and estrogen output
• Preceded by a 4-year menopausal transition
• Average age of menopause is 51, following which
  life expectancy averages 27 to 32 years
• Menopause is considered complete when
  menstruation has ceased for 12 months

3
Characteristics of the Menopause

• Menopause transition is a time of fluctuating
  hormones levels
• Changes in estrogen levels can lead to a variety
  of symptoms - e.g. hot flushes, muscle
  complaints
• Menopause is associated with atherosclerotic
  vascular disease, increased risk for osteoperosis
  
• HRT is prescribed to target many of the somatic
  symptoms research indicates that is may reduce
  the risk for diseases such as osteroperosis (e.g.
  Newman, 1999)

4
Effects of Estrogen on the CNS

• Research suggests that estrogen plays a role in
  the maintenance of neuronal integrity and in CNS
  plasticity (e.g. Brinton, 2001 Toran Allerand,
  et al., 1992).
• Estrogen receptors are found in many regions of
  the brain (e.g. cerebral cortex, hypothalamus,
  amygdala, hippocampus)
• Estrogen influences cognitive functioning by
  increasing enzymes needed to synthesise
  acetylecholine (Luine, 1985).
• Estrogen may enhance synaptic functioning in the
  CA1 area of the hippocampus (Sherwin, 1998).
• The prefrontal cortex and its neural circuitry
  may be a primary site of estrogens effect on the
  brain (Keenan, Ezzat, Ginsgurg, Moore, 2001).

5
Effects of Estrogen on Cognition

• Studies have demonstrated variations in cognitive
  performance during the naturally fluctuating
  hormone levels of the menstrual cycle (e.g.
  Phillips Sherwin, 1992).
• Estrogen loss resulting from a natural or induced
  menopause can adversely affect cognitive
  functioning in otherwise healthy women (Resnick,
  et al., 1997 Sherwin, 1999).
• Long-term use of estrogen replacement therapy by
  postmenopausal women may prevent or delay the
  onset of AD (e.g. Kawas, et al., 1997) and reduce
  risk of dementia (LeBlanc, et al., 2001).
  (controversial)

6
Current controversies surrounding use of HRT

• Use of HRT is currently a very topical issue, for
  example
• Research has linked combined estrogen and
  progestin HRT with increased rates of breast
  cancer and cardiovascular disease in women taking
  it for more than 5 years (Work Group for the
  Womens Health Initiative, 2002).
• Determining the link between HRT and memory
  functioning may help woman make better informed
  decisions

7
The Effects of HRT on Cognitive Functioning

• Zec and Trivedi (2002) reviewed 23 observational
  studies and 19 experimental studies that examined
  the effects of ERT on memory and cognitive
  functioning in postmenopausal women.
• Overall, the ERT groups performed significantly
  better on 28 of the 66 memory measures (42) used
  in the studies.
• There was a higher percentage of significant
  positive findings for the verbal memory measures
  (47) as compared to the visual memory measures
  (31).

8
The Effect of HRT on Cognitive Functioning
(Contd)

• LeBlanc, Janowsky, Chan, Nelson (2001)
  conducted a meta-analysis of 29 cohort studies
  examining effects of HRT on cognitive functioning
  in postmenopausal women.
• Significantly better performance reported on
  tasks of verbal memory, vigilance, reasoning, and
  motor speed, in symptomatic menopausal women
  taking HRT.
• Generally, no benefits were observed in
  asymptomatic women.

9
The Effects of HRT on Cognitive Functioning
(Contd)

• However, this finding has not been supported by
  other studies.
• For example, Zec Travedi (2002) reported a
  positive effect of HRT on cognitive functioning
  in postmenopausal women who were generally
  asymptomatic.
• Polo-Kantola, et al. (1997) reported similar
  cognitive functioning in postmenopausal women who
  experienced significant menopausal symptoms and
  those with minimal symptoms.

10
The Effect of HRT on Cognitive Functioning
(Contd)

• Findings from previous studies have been largely
  inconsistent.
• Some studies have found that estrogen has a
  positive impact on verbal memory (e.g. Jacobs et
  al., 1998 Sherwin, 1998).
• However, there have been studies of equal merit
  that have not supported this finding (e.g.
  Polo-Kantola et al., 1998 Matthews et al.,
  1999).
• Inconsistencies may be due to methodological
  differences and/or problems in the research.

11
A Critique of Previous Research

• Researchers have limited themselves to the use of
  traditional laboratory-type memory tasks (e.g.
  WMS)
• These tools are typically comprised of tasks such
  as learning pairs of unrelated words, reproducing
  simple geometric figures, and learning word lists
• However, the use of these tests has been
  questioned because they do not necessarily mirror
  practical, everyday types of memory tasks
• Limited empirical evidence supporting a
  correlation between traditional memory task
  performance and everyday memory functioning (e.g.
  Tomer et al., 1994)

12
The Concept of Everyday Memory

• Increasing interest in everyday memory since
  the 1970s
• Refers to the memory capacities to manage the
  day-to-day living environment of the individual
• In regard to mid-life women, it has been
  suggested that testing should encompass the
  problems women commonly experience (Warga, 1999).

13
What Makes this Study Novel?

• This study uses a test that simulates everyday
  memory tasks The Rivermead Behavioural Memory
  Test - Extended Version (RBMT-E deWall, Wilson,
  Baddeley, 1994).

14
The Extended Rivermead Behavioural Memory Test

• Consists of 8 subtests
• First and second names
• Appointments Belongings
• Picture recognition
• Face recognition
• Story, immediate and delayed
• Route, immediate and delayed
• Message, immediate and delayed
• Orientation and Date

15
Some Advantages of The RBMT-E

• Sufficiently sensitive to small differences in
  memory performance (e.g. deWall et al., 1994)
• Has been highly acclaimed by clinicians and
  researchers (e.g. Wills, et al., 2000)
• Demonstrated reliability and validity
• Feels like a test of memory
• Very acceptable to older patients

16
Aims and Hypothesis

• Aim To determine the effect of HRT on an
  ecologically-valid memory test (RMBT-E) in a
  sample of postmenopausal women
• Hypothesis In the event that significant
  differences were found in performance between
  HRT-users and non-users
• the performance of HRT-users would be superior
• The area of superiority would be on test(s) of
  verbal memory

17
Method - Participants

• Participants were part of a cohort of 503 women
  recruited from the electoral roll as part of a
  larger study conducted at the Royal Womens
  Hospital The Longitudinal Assessment of Women
  (LAW) study
• 300 women tested in total, only included in
  analysis if
• Postmenopausal
• English first language
• No history of head injury or other neurological
  condition
• No significant sight or hearing difficulties
  (i.e. vision, hearing was corrected, or subject
  was dropped from analyses)

18
Method Participants (Contd)

• 147 women met criteria
• Mean age 59.8 (sd 6.2, range 42 -76)
• 93 classified as non HRT-users (66), 54
  HRT-users (34)
• 28 participants on estrogen replacement therapy,
  26 on combined estrogen and progesterone therapy
• Mixture of naturally and surgically menopausal
  women in sample

19
Method Participants (Contd)
20
Method Participants (Contd)

• No significant differences between the HRT and
  non-HRT group for age, education, premorbid IQ,
  self-ratings of positive and negative affect, and
  overall self-rating of menopausal symptoms.
• However, significant differences in self-ratings
  of loss of interest in sex, t (145) 2.43, p
  lt.05, with non HRT-users reporting more loss of
  interest in sex.

21
Method - Measures

• Recorded age and education level
• Extended Rivermead Behavioural Memory Test
• (Wilson, et al., 1999)
• Wechsler Test of Adult Reading
• (The Psychological Corporation, 2001)
• Positive Negative Affect Schedule
• (Watson, Clark, Tellegen, 1988)
• Greene Climacteric Scale
• (Greene, 1998)
• All measures administered and scored by same
  examiner

22
Method Statistical Analysis

• One-Way Analysis of Covariance (ANCOVA) to assess
  effects of HRT-use v non-use on RBMT-E scores.
  Variables of age, education, premorbid IQ,
  current affective state and self-ratings of
  menopausal symptoms were held constant.

23
Results
plt.05
24
Results (Contd)
ANCOVA Dependent Variable RBMT-E Appointments
Raw Score
p lt .05
25
Results (Contd)
ANCOVA Dependent Variable RBMT-E Appointments
Raw Score
p lt .05
26
Results (Contd)
ANCOVA Dependent Variable RBMT-E Story
Immediate Raw Score
p lt .05
27
Results (Contd)
ANCOVA Dependent Variable RBMT-E Story
Immediate Raw Score
p lt .05
28
Results (Contd)

• Bivariate correlations to determine relationship
  between self-rating of menopausal symptoms
  (Greene Climacteric Scale score) and performance
  on Story Immediate and Appointments.
• GCS score was not significantly related to Story
  Immediate score, r (54) .212, p gt .05, or
  Appointments score, r (54) .116, p gt .05

29
Conclusions

• When variables that may affect cognitive
  functioning were taken into account, HRT-users
  performed significantly better on two everyday
  verbal memory tasks.
• IQ and age were best predictors of performance on
  these tasks
• The hypothesis that if a significant difference
  was found in test performance between the
  HRT-users and non-users, HRT-users would perform
  superiorly, was supported.
• The hypothesis that the area of superiority would
  be on test(s) of verbal memory was supported.

30
Conclusions (Contd)

• These findings are supportive of previous
  research indicating the benefit of estrogen use
  on verbal memory functioning in postmenopausal
  women (e.g. Jacobs et al., 1998 Sherwin, 1998).
• Indicates that the reported benefits of HRT-use
  on aspects of memory functioning are maintained
  when an ecologically valid memory test is used.
• No significant benefit found for HRT-users on the
  delayed story recall subtest this is consistent
  with Sherwin (1988) and Phillips Sherwin (1992)
  who found no effect of HRT on delayed paragraph
  recall.

31
Conclusions (Contd)

• The benefit of HRT-use on test performance was
  independent of self-ratings of menopausal
  symptoms.
• This was consistent with the meta-analytic
  findings reported by Zec and Trivedi (2002).
• Overall, the findings add to the body of
  empirical data on the benefits and risks of HRT
  use

32
Advantages of the Current Study

• Use of an ecologically valid test
• Sample size
• Only postmenopausal women included in analysis
• All measures administered by same examiner
• Participants consisted of Australian women

33
Limitations of the Current Study

• Observational study, so no direct control over
  the type and time-course of HRT-use
• No measure of actual hormone levels on day of
  memory testing
• Exact length of time women had been on HRT was
  unknown

34
Directions for Further Research

• Examining the relationship between performance of
  postmenopausal women on ecologically-valid and
  laboratory-type memory measures.
• Examining other factors that may influence memory
  performance, e.g.
• Attitudes towards ageing
• Knowledge about ageing
• Beliefs about own memory functioning