Measurement Modalities and Number of Vasomotor Symptoms
Measurement Modalities and Number of Vasomotor Symptoms
SWAN is a multisite, multiethnic, longitudinal study that aims to characterize biological and psychosocial changes during the menopausal transition. At their 10th annual visit for SWAN, a subset of women (25 African-American women and 27 white women) from the Pittsburgh site was invited to participate in SWAN FLASHES, an ancillary study including physiological measurement of VMS, methods for which have been described previously. Briefly, the inclusion criteria for SWAN FLASHES included having intact uterus and ovaries, currently experiencing VMS (in the past 2 wk), and not being pregnant. Use of oral contraceptives, hormone therapy, selective serotonin reuptake inhibitor/serotonin-noradrenaline reuptake inhibitor antidepressants, or chemotherapy for breast cancer was exclusionary. Participants were recruited such that approximately equal numbers of African-American and white women were represented in each obesity category (lean, <25 kg/m; overweight, 25-29 kg/m;obese, ≥30.0 kg/m).
Women were assessed for height and weight, given questionnaires (ie, demographics, medical history, and psychological measures), and equipped with a daily diary to be completed before bed and upon waking the next morning, an electronic diary to be completed throughout the day, a physiological hot flash monitor, and a wrist actigraph for four 24-hour ambulatory assessment periods. Procedures were approved by the University of Pittsburgh institutional review board, and all participants provided a written informed consent form.
Before falling asleep each night, participants were asked to report the number of VMS they experienced during that day in their end-of-day diary. In addition, upon waking each morning, participants were asked to report the number of VMS they experienced during the prior night in their morning diary.
Throughout the day, participants were asked to report their VMS at the time of occurrence. They reported these VMS events in three ways: (1) completed an entry in the portable electronic diary (Palm Z22; Palm Inc, Sunnyvale, CA); (2) pressed event mark buttons on the physiological hot flash monitor (3991/2-SCL Single-Channel Hot Flash Monitor BioLog; UFI, Morro Bay, CA), and (3) pressed a button on the wrist actigraph (Minimitter Actiwatch-64; Respironics Inc, Murrysville, PA). A report of VMS on any of these three devices was considered a prospective report of VMS.
VMS were measured physiologically via sternal skin conductance using the BioLog hot flash monitor,aportable device worn around the waist that continuously measures sternal skin conductance in the ambulatory setting. Skin conductance was sampled at 1 Hz from the sternum via a 0.5-V constant-voltage circuit passed between two silver/silver chloride electrodes (UFI) filled with 0.05 M KCl Velvachol/glycol paste. Using the UFI software (DPS version 3.6), all skin conductance rises meeting the criterion of 2-µmho in 30 seconds were flagged for inspection. Those showing the characteristic VMS pattern were coded as a VMS event. Submaximal rises were also considered, and those events showing the characteristic VMS pattern were also coded as events. This procedure has been shown to be reliable. A 20-minute lockout period, during which no further events were coded, was implemented after the start of each VMS event.
Anxiety symptoms were evaluated with the Spielberger StateTrait Anxiety Inventory, a well-validated scale that measures state and trait anxiety; depressive symptoms were evaluated with the widely used and well-validated Center for Epidemiologic Studies Depression Scale; and perceived stress was evaluate with the widely used Cohen Perceived Stress Scale, which queries about one's general appraisal of stress.
Sleep characteristics were measured by both diary report and actigraphy. In their morning diary completed upon waking each morning, participants reported the number of awakenings and total minutes of awakening during the prior night, as well as how that night of sleep compared with a usual night for them (5-point scale ranging from much worse [0] to much better [4]). Self-reported bedtime and rise time were entered for calculations of sleep-wake variables. Actigraphic sleep was measured via a wrist actigraph (Actiwatch-64) worn throughout the ambulatory monitoring period. Actigraphy data were collected in 1-minute epochs and analyzed using the software program Actiware version 5.04. Each awakening was defined as a total activity count greater than a sensitivity threshold of 40. Wakefulness after sleep onset (WASO; total minutes of wakefulness between sleep onset and final wake time) was determined via actigraphy and considered here as the main sleep characteristic given the previously documented associations between reported VMS and wakening during the night.
Demographics, medical history, medication use, menstrual history, and health behaviors were assessed by questionnaires administered during the SWAN FLASHES visit. Race/ethnicity was determined in response to the question, "How would you describe your primary racial or ethnic group?" Education status was determined from self-reported highest grade completed and separated into three categories: high school, some college or vocational school, and college or higher. Menopause status was determined from reported bleeding patterns (perimenopause status was defined as bleeding in the previous 3 mo with a decrease in cycle predictability in the past year or more than 3 mo but less than 12 mo of amenorrhea; postmenopause status was defined as more than 12 mo of amenorrhea). Alcohol use and tobacco use were determined by the current reported number of drinks per day/week/month and cigarettes per day, respectively. Body mass index (BMI) was calculated from height (measured with a fixed stadiometer; Seca, Hanover, MD) and weight (measured with a calibrated balance beam scale; Healthometer, Alsip, IL).
We calculated the number of VMS that were retrospectively reported in daily diaries, prospectively reported, and physiologically measured during daytime and overnight. For each participant, the number of recalled daytime VMS from the end-of-day diary was compared with the number of prospectively reported or physiologically measured VMS that occurred throughout that same day. Similarly, the number of recalled overnight VMS from the morning diary was compared with the number of prospectively reported or physiologically measured VMS that occurred overnight. Difference scores (number of VMS) between these measurement modalities were calculated: (1) end-of-day/morning-recalled, prospectively reported VMS and (2) end-of-day/morning-recalled, physiologically measured VMS.
Because VMS data were collected for multiple days/nights per woman (usually four), generalized estimating equations were used to examine associations between outcomes, covariates, and predictors. State and trait anxiety, depressive symptoms, perceived stress, and WASO were considered in relation to each difference score in separate models. State anxiety, trait anxiety, and depressive symptoms were natural log-transformed for analysis. Covariates were selected based on their association with the outcome at P < 0.15, with age, race/ethnicity, postmenopause status, and BMI included in the final models. We tested interactions between race/ethnicity and psychosocial or sleep characteristics with cross-product terms; where interactions were significant, stratified models were presented. All tests were two-tailed, with an α of 0.05. Analyses were performed with SAS version 9.3 (SAS Institute, Cary, NC).
Methods
Study Population
SWAN is a multisite, multiethnic, longitudinal study that aims to characterize biological and psychosocial changes during the menopausal transition. At their 10th annual visit for SWAN, a subset of women (25 African-American women and 27 white women) from the Pittsburgh site was invited to participate in SWAN FLASHES, an ancillary study including physiological measurement of VMS, methods for which have been described previously. Briefly, the inclusion criteria for SWAN FLASHES included having intact uterus and ovaries, currently experiencing VMS (in the past 2 wk), and not being pregnant. Use of oral contraceptives, hormone therapy, selective serotonin reuptake inhibitor/serotonin-noradrenaline reuptake inhibitor antidepressants, or chemotherapy for breast cancer was exclusionary. Participants were recruited such that approximately equal numbers of African-American and white women were represented in each obesity category (lean, <25 kg/m; overweight, 25-29 kg/m;obese, ≥30.0 kg/m).
Design and Procedures
Women were assessed for height and weight, given questionnaires (ie, demographics, medical history, and psychological measures), and equipped with a daily diary to be completed before bed and upon waking the next morning, an electronic diary to be completed throughout the day, a physiological hot flash monitor, and a wrist actigraph for four 24-hour ambulatory assessment periods. Procedures were approved by the University of Pittsburgh institutional review board, and all participants provided a written informed consent form.
End-of-Day-Recalled and Morning-Recalled VMS
Before falling asleep each night, participants were asked to report the number of VMS they experienced during that day in their end-of-day diary. In addition, upon waking each morning, participants were asked to report the number of VMS they experienced during the prior night in their morning diary.
Prospectively Reported VMS
Throughout the day, participants were asked to report their VMS at the time of occurrence. They reported these VMS events in three ways: (1) completed an entry in the portable electronic diary (Palm Z22; Palm Inc, Sunnyvale, CA); (2) pressed event mark buttons on the physiological hot flash monitor (3991/2-SCL Single-Channel Hot Flash Monitor BioLog; UFI, Morro Bay, CA), and (3) pressed a button on the wrist actigraph (Minimitter Actiwatch-64; Respironics Inc, Murrysville, PA). A report of VMS on any of these three devices was considered a prospective report of VMS.
Physiologically Detected VMS
VMS were measured physiologically via sternal skin conductance using the BioLog hot flash monitor,aportable device worn around the waist that continuously measures sternal skin conductance in the ambulatory setting. Skin conductance was sampled at 1 Hz from the sternum via a 0.5-V constant-voltage circuit passed between two silver/silver chloride electrodes (UFI) filled with 0.05 M KCl Velvachol/glycol paste. Using the UFI software (DPS version 3.6), all skin conductance rises meeting the criterion of 2-µmho in 30 seconds were flagged for inspection. Those showing the characteristic VMS pattern were coded as a VMS event. Submaximal rises were also considered, and those events showing the characteristic VMS pattern were also coded as events. This procedure has been shown to be reliable. A 20-minute lockout period, during which no further events were coded, was implemented after the start of each VMS event.
Psychological Questionnaires
Anxiety symptoms were evaluated with the Spielberger StateTrait Anxiety Inventory, a well-validated scale that measures state and trait anxiety; depressive symptoms were evaluated with the widely used and well-validated Center for Epidemiologic Studies Depression Scale; and perceived stress was evaluate with the widely used Cohen Perceived Stress Scale, which queries about one's general appraisal of stress.
Sleep Characteristics
Sleep characteristics were measured by both diary report and actigraphy. In their morning diary completed upon waking each morning, participants reported the number of awakenings and total minutes of awakening during the prior night, as well as how that night of sleep compared with a usual night for them (5-point scale ranging from much worse [0] to much better [4]). Self-reported bedtime and rise time were entered for calculations of sleep-wake variables. Actigraphic sleep was measured via a wrist actigraph (Actiwatch-64) worn throughout the ambulatory monitoring period. Actigraphy data were collected in 1-minute epochs and analyzed using the software program Actiware version 5.04. Each awakening was defined as a total activity count greater than a sensitivity threshold of 40. Wakefulness after sleep onset (WASO; total minutes of wakefulness between sleep onset and final wake time) was determined via actigraphy and considered here as the main sleep characteristic given the previously documented associations between reported VMS and wakening during the night.
Covariates
Demographics, medical history, medication use, menstrual history, and health behaviors were assessed by questionnaires administered during the SWAN FLASHES visit. Race/ethnicity was determined in response to the question, "How would you describe your primary racial or ethnic group?" Education status was determined from self-reported highest grade completed and separated into three categories: high school, some college or vocational school, and college or higher. Menopause status was determined from reported bleeding patterns (perimenopause status was defined as bleeding in the previous 3 mo with a decrease in cycle predictability in the past year or more than 3 mo but less than 12 mo of amenorrhea; postmenopause status was defined as more than 12 mo of amenorrhea). Alcohol use and tobacco use were determined by the current reported number of drinks per day/week/month and cigarettes per day, respectively. Body mass index (BMI) was calculated from height (measured with a fixed stadiometer; Seca, Hanover, MD) and weight (measured with a calibrated balance beam scale; Healthometer, Alsip, IL).
Statistical Analysis
We calculated the number of VMS that were retrospectively reported in daily diaries, prospectively reported, and physiologically measured during daytime and overnight. For each participant, the number of recalled daytime VMS from the end-of-day diary was compared with the number of prospectively reported or physiologically measured VMS that occurred throughout that same day. Similarly, the number of recalled overnight VMS from the morning diary was compared with the number of prospectively reported or physiologically measured VMS that occurred overnight. Difference scores (number of VMS) between these measurement modalities were calculated: (1) end-of-day/morning-recalled, prospectively reported VMS and (2) end-of-day/morning-recalled, physiologically measured VMS.
Because VMS data were collected for multiple days/nights per woman (usually four), generalized estimating equations were used to examine associations between outcomes, covariates, and predictors. State and trait anxiety, depressive symptoms, perceived stress, and WASO were considered in relation to each difference score in separate models. State anxiety, trait anxiety, and depressive symptoms were natural log-transformed for analysis. Covariates were selected based on their association with the outcome at P < 0.15, with age, race/ethnicity, postmenopause status, and BMI included in the final models. We tested interactions between race/ethnicity and psychosocial or sleep characteristics with cross-product terms; where interactions were significant, stratified models were presented. All tests were two-tailed, with an α of 0.05. Analyses were performed with SAS version 9.3 (SAS Institute, Cary, NC).