Objective Identify symptom clusters that characterize women’s experiences through the late reproductive stage, the menopausal transition and early postmenopause; and explore the influence of the menopausal transition stages and early postmenopause, compared to the late reproductive stage, on the clusters of symptoms women experience. Methods Participants from the Seattle Midlife Women’s Health Study whose symptom calendars were staged for menopausal transition provided data for a total of 6857 occasions. Multilevel latent class analysis was used to identify classes using scores for hot flashes and symptom factors (sleep, cognitive, mood, pain, tension). Results Class 1 included observations of low severity levels for all symptoms, whereas class 2 included low severity hot flashes and moderate severity levels for all other symptom factors. Class 3 included high severity hot flashes with lower severity levels of all other symptom factors. During the early and late menopausal transitions stages and early postmenopause, the likelihood of being in class 3 was significantly greater than being in class 1 relative to the late reproductive stage. There were no significant effects of menopausal transition stages on the likelihood of being in class 2. Conclusions This effort is the first to examine latent classes or clusters of symptoms over the prolonged period from late reproductive stage through early postmenopause. As such, the data contribute to understanding of symptom experiences beyond our early efforts to characterize the late menopausal transition stage.

This analysis revealed similar factor structures across the four stages in that each stage revealed a mood component, a vasomotor component, and a pain component. However, the symptoms differed somewhat in how they grouped from stage to stage. Regression analysis demonstrated that a relationship exists between the symptom factor structures across stages. Controlling for demographic and lifestyle variables, it was revealed that the symptom clusters at the early and late menopausal transition stages and early postmenopause were best predicted by the symptom factor structure of the previous stage.

Aims Review controlled clinical trials of isoflavones and amino acid preparation effects on hot flashes and at least one other symptom including mood, sleep, pain, and cognitive function that women report during the menopausal transition and early postmenopause. Methods An experienced reference librarian searched PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for English-language randomized controlled trials between 2004 to July 2011. Seventeen trials of isoflavones and amino acid effects on hot flashes and one additional symptom were identified. Results In five trials of soy isoflavone preparations, two (6g soy germ extract and 25g soy protein in soy nuts) significantly decreased hot flashes, but no other symptoms. In the seven trials of other isoflavones, six significantly reduced hot flashes; in addition, Red Clover (80 mg) significantly reduced mood symptoms; Rexflavone (350 mg) for women with Kupperman Index > 20 significantly reduced sleep symptoms; two trials had significant reductions for pain: Isoflavone powder (90 mg) and Red Clover (80 mg). The only trial in this systematic review that significantly reduced cognitive symptoms was Red Clover (80 mg). In one trial, Red Clover isoflavone (80 mg/d) significantly relieved hot flashes, mood, pain, and cognitive symptoms. Amino acids yielded no significant results. Equol supplements of 30 mg/d for non-Equol producing women significantly reduced mood symptoms in one trial. The Magnolia Bark Extract combination significantly reduced hot flashes, mood, and sleep symptoms. Conclusions Isoflavone trials yielded significant reductions on hot flashes and co-occurring symptoms during the menopausal transition and postmenopause, but studies require replication with larger sample sizes and attention to measurement of outcomes.

Objective During the menopausal transition and early postmenopause participants in the Seattle Midlife Women's Health Study (SMWHS) were likely to belong to one of three symptom severity classes: severe hot flashes with moderate sleep, mood, cognitive, and pain symptoms (High-severity Hot Flash); moderate levels of all but hot flashes (Moderate Severity); and low levels of all (Low Severity). We tested models of differential effects of hypothalamic-pituitary-ovarian (HPO), hypothalamic-pituitary-adrenal (HPA), and autonomic nervous system (ANS) biomarkers on the three symptom severity classes. Methods SMWHS participants recorded symptoms monthly in diaries and provided overnight urine samples several times per year that were analyzed for estrone, follicle stimulating hormone, cortisol, testosterone, epinephrine and norepinephrine. Multilevel latent class analysis with multinomial regression was used to determine the effects of HPO, HPA, and ANS biomarkers on symptom severity class membership. Results Having lower estrogen levels and higher FSH levels were associated significantly with belonging to the High-severity Hot Flash vs the Low Severity class. Having lower epinephrine and higher norepinephrine levels increased the likelihood of belonging to the High-severity Hot Flash vs the Low Severity class. Having lower epinephrine levels was associated significantly with belonging to the Moderate Severity vs the Low severity class. Cortisol and testosterone were unrelated to symptom severity class membership. Conclusion Association of HPO biomarkers (estrogen, FSH) with the High-severity Hot Flash class was anticipated based on prior hot flash research and associations of HPA biomarkers were as expected based on earlier laboratory studies. Association of lower epinephrine levels with the Moderate Severity class suggests these symptoms may be mediated by the ANS.

This analysis demonstrates that LCA may be useful to identify women who may experience poorer outcomes related to a higher propensity for severe symptoms. Shifting the focus from single symptoms to symptom clusters will aid in the identification of phenotypic profiles, thus facilitating symptom management strategies that can be tailored to meet the needs of individual women.