Symptom clusters among MsFLASH clinical trial participants

Abstract

Objective Women experience multiple co-occurring symptoms (symptom clusters) during the menopausal transition and early postmenopause. Although symptom clusters have been identified among community-dwelling midlife women, to date there have been no studies of midlife participants in clinical trials for hot flashes. Our objective was to identify symptom clusters using standardized measures completed by participants in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health (MsFLASH) clinical trial at baseline including: hot flash interference, and sleep, depressive, anxiety, and pain symptoms. Methods Data from all women randomized to interventions and controls from MsFLASH studies 1, 2, and 3 (N=899) were included; 797 with complete data were used in the analyses. Scores from standardized measures obtained at baseline included: Hot Flash Related Daily Interference Scale (HFRDIS), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire (PHQ 9) measure of depressed mood, Generalized Anxiety Disorder (GAD), and Brief Pain Inventory PEG scores. Latent class analysis was used to identify symptom clusters using standardized scale scores and their established cut points. Results We identified 5 classes using the BIC and AIC criteria. Women in classes 1 and 2 had high hot flash interference levels relative to the others, and class 1 (10.5% of total) included severe hot flash interference, severe sleep symptoms, and moderately severe pain symptoms (hot flash, sleep, pain). In class 2 (14.1%), severe hot flash interference was paired with the severe sleep symptoms, and moderate to severe depressed and anxious mood symptoms and pain (hot flash, sleep, mood, pain). In class 3 (39.6%) women reported moderately severe sleep symptoms with moderate hot flash interference, and low severity mood and pain symptoms (hot flash, sleep). Those in class 4 (7.0%) reported moderate hot flash interference with severe levels of anxiety and depressed mood symptoms, but low levels of other symptoms (hot flash, mood). Women in class 5 (28.7%) reported the lowest levels of all 5 symptoms (low severity symptoms). Conclusions Women meeting hot flash frequency criteria for inclusion in clinical trials exhibited multiple co-occurring symptoms that clustered into identifiable groups according to symptom interference and severity. Variability of symptom profiles between the classes was evident, indicating that the classes were composed of differing symptom types and not simply differing severity levels. These symptom clusters may be useful phenotypes for differentiating treatment effects or evaluating associations with biomarkers or genes.

Validity, cut-points, and minimally important differences for two hot flash-related daily interference scales

“…The links between frequent, severe, or bothersome VMS and sleep problems, 44, 45 mood problems, 46–49 and concentration difficulties 50, 51 have all been previously documented and are consistent with two previously published MsFLASH reports: MsFLASH trial participants’ symptom priorities 52 and symptom clusters. 53 In MsFLASH 02, a companion study was added and it required trial participants to complete a card sort task to indicate which three of twelve possible symptoms they would most like to alleviate. 52 The four most highly rated symptoms were VMS, sleep disruption, concentration impairment, and fatigue.…”

“…Similarly, using pooled data across the MsFLASH trials (n=899), five classes of symptom clusters were found. 53 The classes were: (1) hot flash interference, sleep problems, and pain, (2) hot flash interference, sleep problems, mood problems, and pain, (3) hot flash interference and sleep problems, (4) hot flash interference and mood problems, and (5) low severity of all symptoms. Problems with concentration were not measured as a MsFLASH outcome for use in the clusters analysis.…”

It is not just menopause: symptom clustering in the Study of Women’s Health Across the Nation

“…Women were less likely to be in either of the two latent classes that included hot flashes when they were premenopausal. In the MsFLASH clinical trial, latent class analysis based on hot flash, insomnia, sleep, depressed mood, anxiety and pain symptoms identified 5 classes, 4 of which included hot flashes [ 12 ]. Mishra and Dobson [ 13 ] conducted factor analysis to identify symptom clusters of 17 general health and menopausal symptoms using data from the Australian Longitudinal Study of Women’s Health (ALSWH).…”

“…Im and colleagues [ 17 ] reported race/ethnic differences in reporting of the number and severity of physical symptoms but only in the least symptomatic cluster. The MS-Flash study reported that Black women were more likely than White women to cluster in the severe hot flash, insomnia and pain cluster [ 12 ].…”

Telephone-Based Cognitive Behavioral Therapy for Insomnia in Perimenopausal and Postmenopausal Women With Vasomotor Symptoms

“…Sleep complaints are a common and often bothersome menopausal symptom 1,2 which increase throughout the menopausal transition and early postmenopause. 3,4 Insomnia is associated with increased depression, impaired daytime function, reduced libido, and increased health care utilization, creating a substantial burden for women and society.…”