EMA Methods to Evaluate Triggers of Menopausal Hot Flashes Rebecca C. Thurston, PhD University of Pittsburgh School of Medicine, Department of Psychiatry

Background 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

Background 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 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 Hypotheses Explore emotional antecedents of “false positive” hot flashes –Reported hot flashes lacking physiological concomitant

Rationale 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 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

Overview Screening, Informed Consent Day 1: Ambulatory Sternal Skin Conductance (SCL) Monitoring, Diary, Sleep Sheet, Questionnaires Day 2: Ambulatory SCL Monitoring, Diary, Sleep Sheet Debrief

Diary 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 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 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 monitor

Biolog 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 Flash with Event Mark

Case 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 analysis Clustered data – nonindependence of observations Unequal monitoring time Generalized Estimating Equations Control for time of day

Physiologically Measured Hot Flashes

Emotional Antecedents of Physiologic Hot Flashes Frustration SadnessStressTiredHappyRelaxed In Control * * * * * * * p < 0.05 (Thurston et al., 2005, Psychosom Med)

Psychological Factors Associated with Physiologic Hot Flashes * * * * † † p < 0.1 * p < 0.05 (Thurston et al., 2005, Psychosom Med)

Reporting of Hot Flashes Objective Objective SubjectiveYesNo Yes False positive No394-- (Thurston et al., 2005, Psychosom Med)

Emotional Antecedents of “False Positive” Hot Flashes Frustration SadnessStressTiredHappyRelaxed In Control * * * p < 0.05 (Thurston et al., 2005, Psychosom Med)

Psychological Factors Associated with “False Positive” Hot Flashes * * * * *†† * † † p < 0.1 * p < 0.05 (Thurston et al., 2005, Psychosom Med)

Conclusions ↑ Positive Emotion/Traits ↑ Physiologic Hot Flashes ↑ Negative Emotions/Traits ↑ “False positive” hot flashes  Between and within subjects

Lessons 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 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, 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 Flashes Physical Exertion Physical Effort Caffeine Use † ** p < 0.01 * p = 0.05 ** * †prior to and during Adjusted for time of day

Emotions During and Following Hot Flashes During hot flashes: no significant differences from control Following hot flashes: no significant differences from control

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 and Physiologic Hot Flashes during Sleep (Thurston et al., 2006, Int J Behav Med) SWEL sleep problems

Reported Sleep Problems and Reported Hot Flashes during Sleep ** * † † p = 0.10 * p < 0.05 ** p < (Thurston et al., 2006, Int J Behav Med)