EMA Methods to Evaluate Triggers of Menopausal Hot Flashes

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

2. 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

3. 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

4. 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

5. Secondary Hypotheses • Explore emotional antecedents of “false positive” hot flashes • Reported hot flashes lacking physiological concomitant

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. Biolog Hot Flash monitor

13. 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

14. Skin Conductance Measured Hot Flash with Event Mark

15. Case Crossover Design Monitor Unhook (upon waking) Monitor Hookup 7:00-10:00 am Sleep Day 1 Day 2 Monitoring Period Control Period Hazard Period Flash (Maclure, 1991; Mittleman, 1993, 2001)

16. Data analysis • Clustered data – nonindependence of observations • Unequal monitoring time • Generalized Estimating Equations • Control for time of day

17. Physiologically Measured Hot Flashes

18. Emotional Antecedents of Physiologic Hot Flashes * * * * * * * p < 0.05 In Control Frustration Sadness Stress Tired Happy Relaxed (Thurston et al., 2005, Psychosom Med)

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

20. Reporting of Hot Flashes (Thurston et al., 2005, Psychosom Med)

21. Emotional Antecedents of “False Positive” Hot Flashes * * * p < 0.05 (Thurston et al., 2005, Psychosom Med) Frustration In Control Sadness Stress Tired Happy Relaxed

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

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

24. 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

25. 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

26. 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

27. Acknowledgements James Blumenthal, PhD Andrew Sherwood, PhD Michael Babyak, PhD Janet Carpenter, PhD

29. Physical Exertion Physical Effort Caffeine Use† Behavioral Antecedents of Hot Flashes ** * ** ** p < 0.01 * p = 0.05 †prior to and during Adjusted for time of day

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

31. 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

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

33. ** * † † p = 0.10 * p < 0.05 ** p < 0.001 (Thurston et al., 2006, Int J Behav Med) Reported Sleep Problems and Reported Hot Flashes during Sleep