Stressful life events during the perimenopause: longitudinal observations from the seattle midlife women's health study.

BACKGROUND: Midlife is a time of increased responsibilities for women who have multiple roles including taking care of children, caring for elderly parents, managing households, and working outside the home. With little time for themselves, women additionally experience stressful life events (SLEs). The purpose of this study was to describe the longitudinal patterns of SLEs of women during midlife and to identify predictors of the SLE longitudinal patterns using baseline data of socio-economic factors and demographic characteristics. METHODS: Women who were part of the Seattle Midlife Women's Health Study (SMWHS), a longitudinal study spanning more than 23 years, who had SLEs measured at baseline and at years 2, 7, and 10 were included in these analyses (N = 380 women at baseline). The Life Event Scale (LES), a 70-item scale based on a yes/no response and a Likert-based scoring system with 0 (no effect) to 4 (large effect), was used to determine the total and impact scores of midlife women. The LES was adapted to midlife women from the Norbeck Scale for younger, pregnant women. Analytic strategies consisted of a group-based trajectory model (GBTM) to examine subgroups of women with similar exposure to SLEs using socio-economic factors (gross family income, education, race/ethnicity, employment), demographic variables (age, marital status, being a parent), and menopausal transition stage to differentiate trajectories over time. RESULTS: Approximately 86% of women had medium high exposure to undesirable SLEs with a slight decrease (65.5%), or a sharp decrease (20.1%), over 10 years. The majority (approximately 64%) had moderate, sustained impact ratings, while approximately 35% had impact ratings that decreased over time. Most women (approximately 88%) reported desirable life events, which were sustained over the ten years, and which may help to balance or offset the high ratings of undesirable stressful life events. The rated impact of these desirable events decreased slightly over time for 65% of the sample. Socio-economic factors, demographic variables, and menopausal transition stages were not significant predictors of any of the four GBTMs. CONCLUSION: Midlife women experience SLEs throughout the menopausal transition. Most of these midlife women had had a large amount of sustained stress over 10 years although all trajectories decreased to some extent over time. Since the menopausal transition stages were not significant predictors of the ratings of SLEs, a more complex set of factors, including social as well as biological, may explain the ratings of the women over the course of this ten-year observational study.

Menstrual cycle phase, menopausal transition stage, self-reports of premenstrual syndrome and symptom severity: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The aim of this study was to determine the effects of menstrual cycle phases (postmenses and premenses), self-report of premenstrual syndrome (PMS), late reproductive stages (LRS1 and LRS2), and early menopausal transition (EMT) stage (Stages of Reproductive Aging Workshop [STRAW]) on severity of five symptom groups. METHODS: A subset of Seattle Midlife Women's Health Study participants (n = 290) in either LRS1 or LRS2 or EMT (STRAW+10 criteria) provided daily symptom data for at least one full menstrual cycle during the first year of the study and reported current PMS. Symptom severity was rated (1-4, least to most severe) in the daily diary for five symptom groups (dysphoric mood, neuromuscular, somatic, vasomotor, and insomnia) identified earlier with the same sample ( Maturitas 1996;25:1-10). A three-way analysis of variance was used to test for within- and between-participants effects on symptom severity. RESULTS: Stage had no effect on severity for any of the five symptom groups. Dysphoric mood and neuromuscular and somatic symptom severity (but not vasomotor or insomnia severity) differed significantly across menstrual cycle phases, increasing from postmenses to premenses. Current PMS and premenses cycle phase had significant interactive effects on dysphoric mood and neuromuscular symptoms, but there were no significant interaction effects on somatic, vasomotor, or insomnia symptom severity. CONCLUSIONS: Dysphoric mood, neuromuscular, and somatic symptoms exhibit cyclicity and are influenced by current PMS. Late reproductive stages and EMT stage do not have significant effects on the five symptom groups. Vasomotor or insomnia symptoms do not exhibit significant cyclicity from postmenses to premenses and are not affected by current PMS. Future studies of symptom cyclicity and reproductive aging including daily symptom data across an entire menstrual cycle in samples including women in late menopausal transition stage are essential to capture the effects of both cyclicity and self-reported PMS to capture symptom severity reports at their peak.

Transitioning to the menopausal transition: a scoping review of research on the late reproductive stage in reproductive aging.

IMPORTANCE AND OBJECTIVE: In 2001 Staging Reproductive Aging Workshop conferees described the late reproductive stage (LRS) of reproductive aging as preceding the onset of the menopausal transition, yet there has been little attention to this aspect of reproductive aging. The aim of this scoping review was to examine scientific publications characterizing the LRS to map what is known about this stage with particular focus on reproductive endocrine patterns, menstrual cycle changes, and symptoms. METHODS: The initial search strategy included PubMed and CINAHL searches for the phrase LRS and "human." Given a low yield of research articles, a second stage used "late reproductive age" (LRA) as a search term. These strategies yielded 9 and 26 research articles, respectively. Publications meeting inclusion criteria (data-based research studies, focus on LRS or LRA and hormonal patterns, menstrual characteristics, and symptoms) published in English were reviewed by coinvestigators. Excluded studies were related to specific diseases, such as cardiovascular disease, and treatment studies. Data were summarized using qualitative methods. To ensure adequate coverage of published research we expanded our review to a third phase in which we identified longitudinal studies of the menopausal transition. DISCUSSION AND CONCLUSIONS: Studies of the LRS focused on: symptoms (anxiety and mood symptoms, bladder symptoms, urinary incontinence, urinary frequency, and nocturia) and associated factors, such as endocrine levels and gene polymorphisms; symptom clusters women experienced during the LRS; cognitive function testing results; changing patterns of physiology such as cytokines and chemokines, lipids, hormone patterns/levels; and association of lifestyle factors such as smoking with hormone levels and symptoms. The LRA search yielded a preponderance of studies of reproductive hormones (such as anti-Mullerian hormone) and menstrual cycle patterns. Remaining studies focused on symptoms, gene variants, health-related behaviors and approaches to classifying menstrual cycles. Longitudinal studies revealed reports of symptoms as well as attempts to classify the progression from the reproductive years to the menopausal transition. Study of the LRS has not been systematic and the limited number and scope of completed studies have yet to contribute a clear and complete picture of the LRS. In some, LRS provided a comparison stage against which to evaluate menopausal transition hormonal and cycle patterns and symptoms. Harmonizing the results of studies of the LRS and LRA is essential to understand more completely women's experiences of the LRS and to allow clinicians to provide better support for women during this time. The LRS also represents an ideal inflection point to promote lifestyle choices that could alter the trajectories of chronic diseases that arise in the fifth, sixth, and seventh decades of women's lives.

Video Summary:http://links.lww.com/MENO/A694.

Sleep symptoms during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

STUDY OBJECTIVES: Describe the severity of getting to sleep, nighttime awakening, and early morning awakening across the menopausal transition (MT) and early postmenopause (PM) and their relationship to age, menopausal transition factors, symptoms, stress-related factors, and health related factors. DESIGN: Cohort. SETTING: community. PARTICIPANTS: 286 women from the Seattle Midlife Women's Health Study cohort. MEASUREMENTS: Participants completed annual menstrual calendars for MT staging, diaries in which they rated their symptoms, stress levels, and perceived health multiple times per year from 1990-2007 and provided first morning urine samples assayed for E1G, FSH, cortisol, and catecholamines. Multilevel modeling (R program) was used for data analysis. RESULTS: Severity of self-reported problems going to sleep was associated with all symptoms, perceived stress, history of sexual abuse, perceived health (-), alcohol use (-) (all P < 0.001), and lower cortisol (P = 0.009), but not E1G or FSH. Severity of nighttime awakening was significantly associated with age, late MT stage, and early PM, FSH, E1G (-), hot flashes, depressed mood, anxiety, joint pain, backache, perceived stress, history of sexual abuse, perceived health (-), and alcohol use (-) (all P < 0.001, except E1G for which P = 0.030). Severity of early morning awakening was significantly associated with age, hot flashes, depressed mood anxiety, joint pain, backache, perceived stress, history of sexual abuse, perceived health (-) (all P < or = 0.001, except E1G for which P = 0.02 and epinephrine (P = 0.038), but not MT stages or FSH. Multivariate models for each symptom included hot flashes, depressed mood, and perceived health. CONCLUSION: Sleep symptoms during the MT may be amenable to symptom management strategies that take into account the symptom clusters and promote women's general health rather than focusing only on the MT.

Undesirable stressful life events, impact, and correlates during midlife: observations from the Seattle midlife women's health study.

PURPOSE: To examine the undesirable stressful life events midlife women experience, including: 1) which life events midlife women reported most frequently; 2) which life events women rated as most undesirable; and 3) whether age, years of education, income, employment, race/ethnicity, marital status, being a parent, and the menopausal transition stage were associated with the impact scores of the life event categories. BACKGROUND: In addition to the menopausal transition, midlife is a time of increased responsibilities for women related to multiple roles such as taking care of children, caring for elderly parents, managing households, and working outside the home. These multiple roles put midlife women at risk for increased stress with little time for themselves in order to relieve stress. METHODS: The sample used in this study is part of a larger longitudinal study, The Seattle Midlife Women's Health Study. Women (N = 380 for Occasion 1) completed the 77-item Life Events Scale on four occasions during the course of the SMWHS: Occasion 1 (1990), Occasion 2 (1992), Occasion 3 (1997), and Occasion 4 (2000). In addition to descriptive analyses of frequency of life events and the undesirable impact of life events, demographic correlates (age, education, income, employment, being a parent as well as marital status, race/ethnicity, and menopausal transition stages) were examined in relation to the stressful life event scores. RESULTS: Highest scores of undesirable life events were for categories of both Financial and Family/Friends over 3 of the 4 occasions. Health and Crime/Legal scores were among the highest for 2 occasions. Impact of the undesirable stressful life events was greatest for categories of Family/Friends; Personal/Social; Work; and, Health. Age, income, marital status, being a parent, and menopausal transition stage were each associated with specific categories of the stressful event impact scores. CONCLUSION: Most commonly reported undesirable life events were not those women described as having the greatest impact. Impact of life event stress reflected women's social roles and connections as seen in the categories with the highest impact scores: Family/Close Friends, Personal/Social, and Work. Menopausal transition stages were related only to undesirable health events.

Self-awareness and the evaluation of hot flash severity: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The purpose of this study was to test the association of two dimensions of self-awareness with hot flash (HF) severity. METHODS: A subset of women from the Seattle Midlife Women's Health Study (N = 232) provided data for these analyses. Structural equation modeling was used to evaluate two dimensions of self-awareness (Internal States Awareness [ISA] and Self-Reflectiveness [SR]), and secondary factors of perceived stress, anxiety, and attitudes toward menopause as continuous with earlier life, health perceptions, and menopausal stage with respect to HF severity. The measurement and structural models were tested with a maximum likelihood missing values estimator and displayed good model fit. RESULTS: Women with greater ISA reported greater HF severity (ß = 0.17, P < 0.05). In addition, women in later menopausal transition stages reported greater HF severity and those with attitudes of continuity toward menopause reported less severe HFs (ß = 0.20, P < 0.01, ß = -0.30, P < 0.001, respectively). SR was not related to HF severity. Women with higher levels of SR reported greater perceived stress levels (ß = .51, P < 0.001), and those with greater perceived stress reported greater anxiety levels (ß = 0.63, P < 0.001) and attitudes of continuity toward menopause as less continuous with earlier life (ß = -0.30, P < 0.001). CONCLUSIONS: ISA (balanced self-awareness) was associated with greater HF severity, suggesting that enhanced balanced self-awareness may promote women's ability to evaluate their symptom experience. A multidimensional construct of self-awareness, perceived stress, anxiety, and attitude toward menopause are all plausible targets for future intervention studies of symptom management.

Well-being during the menopausal transition and early postmenopause: a within-stage analysis.

PURPOSE: To identify whether menopausal transition (MT)-related factors--including MT stage, hot flash severity, levels of estrone glucuronide (E1G) and follicle stimulating hormone (FSH); number of negative life events; or personal resources of mastery and social support--are associated with stage specific well-being. METHODS: Women from the Seattle Midlife Women's Health Study (N=334) provided at least one annual health questionnaire and a menstrual calendar; a subset provided first morning voided urine specimens assayed for E1G and FSH. Descriptive statistics were calculated and Pearson's product-moment correlations were estimated. RESULTS: Mean levels of well-being were the same across MT stages (4.1, range 1.8-5.9). Physiologic variables were not significantly correlated with well-being: E1G levels (r = - .11 to 0.16), FSH levels (r = - .17 to .20) and hot flash severity (r = - .07 to .05). Significant correlations were observed between well-being and number of negative life events (r = - .48 to - .33, p < or = 0.01), mastery (r = .51-.64, p < or = 0.01), and satisfaction with social support (r = .04 non-significant) to r =.41, (p < or = 0.01). CONCLUSION: The association of well-being with life events and personal resources, and not MT-related indicators, hormone levels or vasomotor symptoms, supports work by other researchers. Further study is needed to determine whether patterns of well-being vary across the MT, and if so, what might predict that variability.

The challenges of midlife women: themes from the Seattle midlife Women's health study.

BACKGROUND: Midlife, the period of the lifespan between younger and older adulthood, has been described as a period of transition in women's lives. Investigators studying midlife have focused on women 40 to 65 years of age, who typically experience multiple social, psychological and biological challenges, among them the menopausal transition. Investigators have reported a diverse array of stressful events, for example, health concerns, family problems, work-related issues, deaths, frustrated goal attainment, and financial worries; however, none have identified which life events midlife women experience as the most salient. The purpose of this study was to understand the meaning behind the experiences that midlife women identify as the most challenging. METHODS: Participants were enrolled in The Seattle Midlife Women's Health Study, a longitudinal study spanning up to 23 years. Summative content analysis, incorporating manifest and latent analysis approaches, was used to identify life experiences that women described as the most challenging looking back over 15 years of being in the study. Eighty-one women responded to the question, "Since you have been in our study (since 1990 or 1991), what has been the most challenging part of life for you?" RESULTS: Women identified the most challenging aspects of midlife as changing family relationships, re-balancing work/personal life, re-discovering self, securing enough resources, and coping with multiple co-occurring stressors. Within these themes the most frequently reported challenges were: multiple co-occurring stressors, divorce/breaking up with a partner, health problems of self, and death of parents. Few women mentioned menopause as the most challenging aspect of their lives. CONCLUSION: Women found themselves searching for balance in the midst of multiple co-occurring stressors while coping with losses and transitions, for some in a context of limited resources. Menopause was infrequently mentioned. Future research to identify the challenges experienced by more diverse populations of women and further understanding of the dynamics among multiple co-occurring stressors is needed to provide individualized health care appropriately to midlife women.

Polymorphisms in Estrogen Synthesis Genes and Symptom Clusters During the Menopausal Transition and Early Postmenopause: Observations From the Seattle Midlife Women's Health Study.

During the menopausal transition and early postmenopause, participants in the Seattle Midlife Women's Health Study (SMWHS) experienced one of the three symptom severity clusters identified through latent class analysis: severe hot flashes with moderate sleep, mood, cognitive, and pain symptoms (high-severity hot flash); low-severity hot flashes with moderate levels of all other symptom groups (moderate severity); and low levels of all symptom groups (low severity). In an effort to determine whether gene polymorphisms were associated with these symptom severity classes, we tested associations between gene polymorphisms in the estrogen synthesis pathways (cytochrome P450 19 [CYP 19] and 17 beta hydroxysteroid dehydrogenase [ 17HSDB1]) and the three symptom severity clusters. SMWHS participants ( N = 137) recorded symptoms monthly in diaries and provided buccal smears for genotyping. Multilevel latent class analysis with multinomial regression was used to determine associations between gene polymorphisms and symptom severity clusters. Only the 17HSDB1 polymorphisms ( rs615942 and rs592389) were associated significantly with the high-severity hot flash cluster versus the low-severity symptom cluster. None of the polymorphisms was associated with the moderate-severity cluster versus the low-severity symptom cluster. Findings of associations of the 17HSDB1 polymorphisms with the high-severity hot flash symptom cluster are consistent with those of an association between 17HSDB1 polymorphisms and hot flashes in the Study of Women and Health Across the Nation population and our previous findings of associations between these polymorphisms with greater estrone levels.

Symptoms during the menopausal transition and early postmenopause and their relation to endocrine levels over time: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: To determine whether hot flashes, depressed mood, sleep, cognitive and sexual symptoms correlate with urinary follicle-stimulating hormone (FSH), estrone (E(1)G), and testosterone (T) and with each other during the menopausal transition and early postmenopause (PM). METHODS: Forty-one women who transitioned from middle or late transition stage to PM rated symptoms and provided monthly urine specimens as part of a longitudinal study of the menopausal transition. RESULTS: Correlations between endocrine levels and symptom severity ratings over time revealed that hot flash severity was significantly and positively related to FSH and negatively to E1 G. Vaginal dryness was positively correlated with FSH and negatively correlated with T. Decreased sexual desire was correlated negatively with E(1)G levels. Forgetfulness was positively correlated with FSH; difficulty concentrating was negatively correlated with T. Severity of sleep symptoms and depressed mood were not correlated with E(1)G, FSH, or T. Correlations among the symptoms revealed that severity of hot flashes was associated with sleep disruption and forgetfulness. Depressed mood was correlated with sleep disruption, difficulty concentrating, and decreased sexual desire but not with hot flashes or vaginal dryness. Awakening during the night was correlated with decreased sexual desire and vaginal dryness, as well as hot flashes. Forgetfulness was associated with hot flashes and difficulty concentrating, whereas difficulty concentrating was associated with depressed mood and early awakening. CONCLUSIONS: Symptoms many women experience during the menopausal transition and early PM are related to different endocrine levels (FSH, E(1)G, and T).

Hot flash severity in hormone therapy users/nonusers across the menopausal transition.

OBJECTIVES: The purpose of this study was to examine the pattern of and factors that influence hot flash severity across the menopausal transition (MT) and early postmenopause (PM). METHODS: Women from the Seattle Midlife Women's Health Study (N=302) provided data for these analyses: at least one annual health questionnaire and a menstrual calendar. A subset of women provided a first morning voided urine specimen from 1997 through 2005. Urine samples were assayed for estrone glucuronide and FSH. Linear mixed effects modeling was used to identify change in hot flash severity scores over time, including the relationship to age, MT-related, psychosocial and lifestyle factors. RESULTS: Increases in hot flash severity were associated with late transition stage, early postmenopause, use of HRT, duration of early transition stage, age of entry into early PM and level of FSH. Age of entry into early transition and estrone levels were associated with decreased hot flash severity. Not associated with hot flash severity were being in early transition stage, age of entry into or duration of late transition stage and all of the psychosocial (anxiety, stress, depressed mood) and lifestyle variables (BMI, activity level, sleep, alcohol use). CONCLUSIONS: Variables associated with reproductive aging independently predicted changes in hot flash severity; psychosocial and lifestyle variables did not. The effect of age dropped out when factors associated with reproductive aging were considered. Use of HRT ameliorated but did not eliminate severe hot flashes suggesting that there is room for alternative approaches less likely to cause harm.

Depressed mood during the menopausal transition: is it reproductive aging or is it life?

BACKGROUND: Although there has been noteworthy attention to both depressed mood symptoms and majordepressive disorder during the menopausal transition (MT), recently investigators have questioned whether there is an over-pathologizing of the MT by emphasizing hormonal effects on depression and deflecting attention from the everyday conditions of women's lives as they relate to depressed mood. In addition, fluctuation of mood over short periods of time may not be captured by measures of depressed mood symptoms such as the CESD, especially when administered using a reference period such as a week or more. The purpose of this study was to examine the association of menopausal transition factors, health-related factors, stress factors, social factors and symptoms with repeated measures of depressed mood reported for a 24 h period. METHODS: Seattle Midlife Women's Health Study participants (n = 291, 6977 observations) provided data from 1990 to 2013 including annual questionnaires, symptom diaries and urine specimens assayed for hormones several times per year. Multilevel modeling was used to test bivariate and multivariable models accounting for depressed mood severity. RESULTS: In individual models with age as the measure of time, being in early postmenopause, exercising more, and being partnered were associated with less severe depressed mood; greater perceived stress, having a history of sexual abuse, difficulty getting to sleep, early awakening, and awakening at night were each associated with higher depressed mood severity. In a multivariable model (n = 234, 6766 observations), being older, being in the early postmenopause, exercising more, being partnered, were associated with less severe depressed mood; reporting greater perceived stress, history of sexual abuse, difficulty getting to sleep and early awakening were associated with more severe depressed mood. CONCLUSIONS: Clinicians need to consider the context in which midlife women experience the menopausal transition and mood symptoms as well as hormonal transitions during this part of the lifespan.

Polymorphisms in the estrogen synthesis and metabolism pathways and symptoms during the menopausal transition: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The purpose of this study was to determine whether polymorphisms in the estrogen synthesis and metabolism pathways are associated with women's vasomotor symptom experiences during the menopausal transition. DESIGN: In 2002, a subset of women enrolled in the Seattle Midlife Women's Health Study since 1990 (N = 174) provided a buccal smear for genotyping. Women were recruited by complete ascertainment of selected multiethnic neighborhoods in 1990. Participants were midlife women with a mean age of 53 years in 2005, well educated, employed, married, and represented a multiethnic population. Genotyping was done for the following polymorphisms: CYP1A1m2; CYP1B1*2 and CYP1B1*3; CYP17 5'UTR; CYP19 3'UTR; CYP19 (TTTA)n; including CYP19 7r and CYP19 7(r-3); CYP19 8r and CYP19 11r; and ESR1PvuII and ESR1XbaI. Women rated their vasomotor symptom severity in diaries on days 5, 6, and 7 of the menstrual cycle or on a constant date each month for women skipping periods. Menopausal transition stage was determined from daily menstrual calendars. First voided urine specimens provided several times each year were assayed for estrone glucuronide. RESULTS: Women with the CYP19 11r polymorphism reported more severe and frequent hot flashes during the middle and late menopausal transition stages and postmenopause and higher E1G levels during middle and late stages. None of the other polymorphisms studied were related to hot flashes or to estrone glucuronide levels. CONCLUSIONS: These findings suggest a possible role for CYP19 polymorphisms in estrogen levels and in vasomotor symptoms during the menopausal transition that warrants further study in larger and more diverse populations of women.

The Seattle Midlife Women's Health Study: a longitudinal prospective study of women during the menopausal transition and early postmenopause.

BACKGROUND: The need for longitudinal, population-based studies to illuminate women's experiences of symptoms during the menopausal transition motivated the development of the Seattle Midlife Women's Health Study. METHODS: Longitudinal, population-based study of symptoms women experienced between the Late Reproductive stage of reproductive aging and the early postmenopause. Data collection began in 1990 with 508 women ages 35-55 and continued to 2013. Entry criteria included age, at least one period in past 12 months, uterus intact and at least 1 ovary. Women were studied up to 5 years postmenopause. Data collection included yearly health questionnaires, health diaries, urinary hormonal assays, menstrual calendars and buccal cell smears. RESULTS: Contributions of the study included development of a method for staging the menopausal transition; development of bleeding criteria to differentiate bleeding episodes from intermenstrual bleeding from menstrual calendars; identification of hormonal changes associated with menopausal transition stages; assessment of the effects of menopausal transition factors, aging, stress-related factors, health factors, social factors on symptoms, particularly hot flashes, depressed mood, pain, cognitive, sexual desire, and sleep disruption symptoms, and urinary incontinence symptoms; identification of naturally occurring clusters of symptoms women experienced during the menopausal transition and early postmenopause; and assessment of gene polymorphisms associated with events such as onset of the early and late menopausal transition stages and symptoms. CONCLUSIONS: Over the course of the longitudinal Seattle Midlife Women's Health Study, investigators contributed to understanding of symptoms women experience during the menopausal transition and early postmenopause as well as methods of staging reproductive aging.

Perimenopause: an update.

The field of perimenopause research is advancing our understanding of the physiological changes related to the menopausal transition and approaches to managing symptoms and preventing disease of advanced age. The impact of the perimenopause on women's health will become evident with the aging of the population.

Endocrine biomarkers and symptom clusters during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: During the menopausal transition and early postmenopause, participants in the Seattle Midlife Women's Health Study 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 the differential effects of hypothalamic-pituitary-ovarian (HPO) axis, hypothalamic-pituitary-adrenal (HPA) axis, and autonomic nervous system (ANS) biomarkers on the three symptom severity classes. METHODS: The Seattle Midlife Women's Health Study participants recorded symptoms monthly in diaries and provided overnight urine samples several times per year that were analyzed for estrone, follicle-stimulating hormone (FSH), cortisol, testosterone, epinephrine, and norepinephrine. Multilevel latent class analysis with multinomial regression was used to determine the effects of HPO axis, HPA axis, and ANS biomarkers on symptom severity class membership. RESULTS: Having lower estrogen and higher FSH levels was significantly associated with belonging to the high-severity hot flash class versus the low-severity class. Having lower epinephrine and higher norepinephrine levels increased the likelihood of belonging to the high-severity hot flash class versus the low-severity class. Having lower epinephrine levels was significantly associated with belonging to the moderate-severity class versus the low-severity class. Cortisol and testosterone were unrelated to symptom severity class membership. CONCLUSIONS: The association of HPO axis biomarkers (estrogen and FSH) with the high-severity hot flash class is anticipated based on prior hot flash research, and the associations of HPA axis biomarkers are as expected based on earlier laboratory studies. The association of lower epinephrine levels with the moderate-severity class suggests that these symptoms may be mediated by the ANS.

Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: a systematic review.

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 and 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 25 g 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/day) significantly relieved hot flashes, mood, pain, and cognitive symptoms. Amino acids yielded no significant results. Equol supplements of 30 mg/day 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.

Consequences of incontinence for women during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: Although urinary incontinence becomes more prevalent as women age, little is known about the outcomes of urinary incontinence in midlife women. Our aim was to determine the effects of urinary incontinence (stress and urge) on mood (depressed mood, anxiety), perceptions of self (self-esteem, mastery, perceived health), attitudes toward midlife (attitudes toward aging, attitudes toward menopause), and consequences for daily living (interference with relationships, interference with work, sexual desire, physical activity, awakening at night, social support, stress), taking into account the effects of aging METHODS: A subset of Seattle Midlife Women's Health Study participants (n = 299, with up to 2,206 observations) provided data during the late reproductive stage, early menopausal transition, late menopausal transition, and early postmenopause, including menstrual calendars, annual health questionnaire since 1990, and symptom diaries. Multilevel modeling (R program) was used to test models accounting for urinary incontinence outcomes. RESULTS: Stress urinary incontinence and urge urinary incontinence were significantly associated with lower self-esteem (P = 0.01 and P = 0.001, respectively) and mastery (P < 0.001, stress urinary incontinence and urge urinary incontinence), with age included in the models as a measure of time. Urinary incontinence's effects on mood symptoms, attitudes toward aging, attitudes toward menopause, perceived health, and consequences for daily living were not significant (P > 0.05). CONCLUSIONS: Urinary incontinence during the menopausal transition and early postmenopause seems to affect perceptions of self--but not mood, attitudes toward midlife, or consequences for daily living--in this midlife population. Appropriate therapies for urinary incontinence during midlife may promote higher levels of self-esteem and a greater sense of mastery by older women.

Symptom clusters during the late reproductive stage through the early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The aim of this study was to identify symptom clusters that characterize women's experiences through the late reproductive stage, the menopausal transition, and early postmenopause and to explore the influence of the menopausal transition stages and early postmenopause, compared with that of 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 the menopausal transition provided data for a total of 6,857 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 transition 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 the menopausal transition stages on the likelihood of being in class 2. CONCLUSIONS: This effort is the first to examine the latent classes or clusters of symptoms during the prolonged period from late reproductive stage to early postmenopause. As such, the data contribute to the understanding of symptom experiences beyond our early efforts to characterize the late menopausal transition stage.

Symptom interference with work and relationships during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The aim of this study was to describe the changes in symptom interference during the menopausal transition (MT) stages and early postmenopause (PM), including the effects of age, MT-related factors (estrone, follicle-stimulating hormone, testosterone, MT stages), symptoms (hot flashes, depressed mood, awakening during the night, anxiety, backache, joint pain, forgetfulness, and difficulty concentrating), health-related factors (perceived health), and stress-related factors (perceived stress, cortisol). METHODS: A subset of Seattle Midlife Women's Health Study participants provided data during the late reproductive, early and late MT stages, or early PM (n = 184), including menstrual calendars for staging the MT; annual health reports completed between 1990 and 2008; morning urine samples assayed for estrone glucuronide, follicle-stimulating hormone, and cortisol; and symptom diary ratings several times each year. Interference was rated in the diary along with symptoms, perceived health, and stress. Multilevel modeling with an R program was used to test the patterns of symptom interference related to age, MT-related factors, symptoms, and health- and stress-related factors, with as many as 5,656 observations. Median age was 47.4 years. RESULTS: Interference with work was significantly associated with individual covariates such as perceived health, stress, hot flashes, depressed mood, anxiety, difficulty getting to sleep, awakening during the night, early morning awakening, backache, joint pain, forgetfulness, and difficulty concentrating (for hot flashes, P = 0.01; all others, P < 0.001). A final multivariate model included perceived health, stress, depressed mood, and difficulty concentrating. Interference with relationships was significantly associated with age and individual covariates such as perceived health, estrone, perceived stress, depressed mood, anxiety, sleep symptoms, backache, joint pain, forgetfulness, and difficulty concentrating (for estrone, P = 0.03; all others, P < 0.001). A final multivariate model included perceived health, stress, depressed mood, anxiety, difficulty concentrating, and awakening during the night. CONCLUSIONS: Women's reports of how much the way they felt interfered with work and relationships were influenced by both their perceived health and stress levels. Interference was also influenced by depressed mood and difficulty concentrating, suggesting that these two symptoms may be most important to address, to enhance functioning during the MT and early PM.