ABSTRACT: Background:Patterns of symptom clustering in midlife women may suggest common underlying mechanisms or may identify women at risk of adverse health outcomes or, conversely, likely to experience healthy aging. This paper assesses symptom clustering in the Study of Women's Health Across the Nation (SWAN) longitudinally by stage of reproductive aging and estimates the probability of women experiencing specific symptom clusters. We also evaluate factors that influence the likelihood of specific symptom clusters and assess whether symptom clustering is associated with women's self-reported health status. Methods:This analysis includes 3289 participants in the multiethnic SWAN cohort who provided information on 58 symptoms reflecting a broad range of physical, psychological and menopausal symptoms at baseline and 7 follow-up visits over 16 years. We conducted latent transition analyses to assess symptom clustering and to model symptomatology across the menopausal transition (pre, early peri-, late peri- and post-menopausal). Joint multinomial logistic regression models were used to identify demographic characteristics associated with premenopausal latent class membership. A partial proportional odds regression model was used to assess the association between latent class membership and self-reported health status. Results:We identified six latent classes that ranged from highly symptomatic (LC1) across most measured symptoms, to moderately symptomatic across most measured symptoms (LC2), to moderately symptomatic for a subset of symptoms (vasomotor symptoms, pain, fatigue, sleep disturbances and physical health symptoms) (LC3 and LC5) with one class (LC3) including interference in life activities because of physical health symptoms, to numerous milder symptoms, dominated by fatigue and psychological symptoms (LC4), to relatively asymptomatic (LC6). In pre-menopause, 10% of women were classified in LC1, 16% in LC2, 14% in LC3 and LC4, 26% in LC5, and 20% in LC6. Intensity of vasomotor and urogenital symptoms as well as sexual desire) differed minimally by latent class. Classification into the two most symptomatic classes was strongly associated with financial strain, White race/ethnicity, obesity and smoking status. Over time, women were most likely to remain within the same latent class as they transitioned through menopause stages (range 39-76%), although some women worsened or improved. The probability of moving between classes did not differ substantially by menopausal stage. Women in the highly symptomatic classes more frequently rated their health as fair to poor compared to women in the least symptomatic class. Conclusion:Clear patterns of symptom clustering were present early in midlife, tended to be stable over time, and were strongly associated with self-perceived health. Notably, vasomotor symptoms tended to cluster with sleep disturbances and fatigue, were present in each of the moderate to highly symptomatic classes, but were not a defining characteristic of the symptom clusters. Clustering of midlife women by symptoms may suggest common underlying mechanisms amenable to interventions. Given that one-quarter of midlife women were highly or moderately symptomatic across all domains in the pre-menopause, addressing symptom burden in early midlife is likely critical to ameliorating risk in the most vulnerable populations.
