EMA Methods to Evaluate EMA Methods to Evaluate Triggers of Menopausal Triggers of Menopausal

Hot FlashesHot Flashes

Rebecca C. Thurston, PhDRebecca C. Thurston, PhDUniversity of Pittsburgh School of Medicine, University of Pittsburgh School of Medicine,

Department of PsychiatryDepartment of Psychiatry

BackgroundBackground

• Hot flashes experienced by most (70%) women during menopause

• Associated with impairments in quality of life, mood, sleep

• Etiology and triggers not well understood

• “Stress” leading reported trigger

BackgroundBackground

• Lack of rigorous research– Retrospective, one-time self-report

measures: emotions and hot flashes

– Irregular, mundane, frequent experiences

– Memory and reporting biases

• Need for prospective measurement

• Physiologic measures of hot flashes

Primary HypothesesPrimary Hypotheses

• Within individuals: Physiologic hot flashes more likely after

↑ Negative emotion↓ Positive emotion

• Between individuals: Women with more physiologic hot flashes

↑Negative psychological functioning

Secondary HypothesesSecondary Hypotheses

• Explore emotional antecedents of “false positive” hot flashes

–Reported hot flashes lacking physiological concomitant

Rationale for Use of EMA MethodsRationale for Use of EMA Methods

• Prospective reports:– Emotions– Hot flashes

• Avoid memory biases

• Physiologic measures of hot flashes

• Compare subjective/objective hot flashes

• Characterize naturally-occurring emotions and hot flashes in “real life” environment

Sample CharacteristicsSample Characteristics

• N = 42

• Perimenopausal or postmenopausal

• Age 40 to 60

• At least one hot flash a day

• Not taking medications known to impact hot flashes

OverviewOverview

Screening, Informed Consent

Day 1: Ambulatory Sternal Skin Conductance (SCL) Monitoring, Diary,

Sleep Sheet, Questionnaires Day 2: Ambulatory SCL Monitoring, Diary,

Sleep Sheet

Debrief

DiaryDiary

• Fixed time sampling (primary)

– 3 times/hour, waking hours

– Emotion report within 30 min before hot flash

• Event sampling (secondary):

– Entry at experience of hot flash

• Temporal frame: Current state

– Avoid any memory effects

Diary Assessment MethodDiary Assessment Method• Paper diary

– Low cost, minimal start up, minimal particiapant training, good for population?

• Prompting method– Watchminder Training and Reminder System

– Program to sleep schedule

– Sync time with hot flash monitor

• Compliance– Careful explanation, instruction page, practice entry

– Emphasize importance of completion time accuracy

Diary ContentDiary Content• Time• Location (home, work, car, other)• Activities (walking, eating, talking/listening, etc)• Occurrence and intensity of hot flash• Emotions

– Frustrated, sad, stressed– Tired – Relaxed, happy, in control

• Use of tobacco, caffeine, alcohol• Sleep Sheet

Biolog Hot Flash monitorBiolog Hot Flash monitor

Biolog Hot Flash MonitorBiolog Hot Flash Monitor

• Sampling: continuous recording of sternal skin conductance (1 Hz)

– Subjective event markers: time/date stamp– Can’t get wet, no rigorous exercise

• Compliance – Careful instruction, instruction sheet, number to call with problems– Allow to take off in am to shower– Initially only one night

Skin Conductance Measured Hot Skin Conductance Measured Hot Flash with Event MarkFlash with Event Mark

Case Crossover DesignCase Crossover Design

Monitor Hookup 7:00-10:00 am

Sleep

Hazard Period

Flash

Day 1

Day 2

Monitor Unhook (upon

waking)

Control Period

Monitoring Period

(Maclure, 1991; Mittleman, 1993, 2001)

Data analysisData analysis

• Clustered data – nonindependence of observations

• Unequal monitoring time

• Generalized Estimating Equations

• Control for time of day

Physiologically Measured Hot Physiologically Measured Hot FlashesFlashes

0

0.2

0.4

0.6

0.8

10-

1

1-2

2-3

3-4

4-5

5-6

6-7

7-8

8-9

9-10

10-1

1

11-1

2

12-1

3

13-1

4

14-1

5

15-1

6

16-1

7

17-1

8

18-1

9

19-2

0

20-2

1

21-2

2

22-2

3

23-2

4

Hour

Ho

t fl

ash

es p

er s

ub

ject

day

Emotional Antecedents of Emotional Antecedents of PhysiologicPhysiologic Hot Flashes Hot Flashes

0

0.5

1

1.5

2O

R o

f Hot

Fla

sh

Fru

stration

Sad

ness

Stress

Tired

Hap

py

Relaxed

In

Con

trol

*

*

*

** *

* p < 0.05(Thurston et al., 2005, Psychosom Med)

Psychological Factors Associated Psychological Factors Associated with with PhysiologicPhysiologic Hot Flashes Hot Flashes

0

5

10

15

20

25

30

Low Medium High

Ph

ysio

logi

c H

ot F

lash

es (

n)

State Anxiety

Trait Anxiety

Negative Attitudes

* *** †

† p < 0.1* p < 0.05

(Thurston et al., 2005, Psychosom Med)

Reporting of Hot FlashesReporting of Hot Flashes ObjectiveObjective

SubjectiveSubjective

YesYes NoNo

YesYes 347347 208208

False False positivepositive

NoNo 394394 ----

(Thurston et al., 2005, Psychosom Med)

Emotional Antecedents of Emotional Antecedents of “False “False Positive”Positive” Hot Flashes Hot Flashes

0

0.5

1

1.5

2

OR

Fal

se P

osit

ive

Hot

Fla

sh

Fru

stration

Sad

ness

Stress

Tired

Hap

py

Relaxed

In

Con

trol

*

*

* p < 0.05(Thurston et al., 2005, Psychosom Med)

Psychological Factors Associated with Psychological Factors Associated with “False Positive”“False Positive” Hot Flashes Hot Flashes

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

low medium high

Fal

se p

osit

ive

repo

rtin

g ra

te

DepressionState anxietyTrait anxietyNegative attitudesSomatization

**

**

*† †*

†

† p < 0.1* p < 0.05

(Thurston et al., 2005, Psychosom Med)

ConclusionsConclusions

↑ Positive Emotion/Traits

↑ Physiologic Hot Flashes

↑ Negative Emotions/Traits

↑ “False positive” hot flashes

Between and within subjects

Lessons LearnedLessons Learned• Paper diaries convenient, but

understanding compliance an issue– New study using electronic diaries:

date/time stamp

– Expanded questions about hot flashes

– Beeper imbedded within palm

– Reminder beep if miss entry (5 minute)

– Instruct that we know when they fill out

– Electronic diaries tolerated well

Lessons LearnedLessons Learned

• Nice to take off monitor in am, but better to have 24 hours of data– Capture circadian rhythm more accurately

– Normalize monitor durations

– Careful recording of start/stop times

– Ideally: More days of monitoring due to variability in hot flashes between days

– Monitor tolerated well during sleep

Instructions, instructionsInstructions, instructions

• Participant training/orientation critical to getting good data

• Practice diary entry/use of monitor

• Interim phone calls

• Documentation to take home

• Way to get in touch with study staff

Acknowledgements

James Blumenthal, PhD

Andrew Sherwood, PhD

Michael Babyak, PhD

Janet Carpenter, PhD

Behavioral Antecedents of Hot FlashesBehavioral Antecedents of Hot Flashes

0

1

2

3

4

5

OR

of H

ot F

lash

Physical Exertion

Physical Effort

Caffeine Use†

** p < 0.01* p = 0.05

**

**

*

†prior to and during

Adjusted for time of day

Emotions During and Emotions During and Following Hot FlashesFollowing Hot Flashes

• During hot flashes: no significant differences from control

• Following hot flashes: no significant differences from control

Don’t forget about nighttime!Don’t forget about nighttime!• Women tolerate overnight monitoring well

• Sleep an issue in women with hot flashes

• Physiologic hot flash measures important during sleep

• Now more complete sleep data:– More extensive sleep diary– Better questionnaire measures– Actigraphy

Reported Sleep Problems andReported Sleep Problems and Physiologic Hot Flashes Physiologic Hot Flashes

during Sleepduring Sleep

(Thurston et al., 2006, Int J Behav Med)

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Dairy wakening Diary times outof bed

Sleep Problems

Rat

e R

atio

(R

R)

Ph

ysio

logi

c H

ot F

lash

es

SWEL sleep problems

Reported Sleep Problems and Reported Sleep Problems and Reported Hot Flashes during Reported Hot Flashes during

SleepSleep

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

SWEL sleepproblems

Diary wakenings Diary times outof bed

Sleep Problems

RR

Rep

orte

d H

ot F

lash

es

**

*

†

† p = 0.10* p < 0.05** p < 0.001(Thurston et al., 2006, Int J Behav Med)