Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Vasomotor symptoms and the risk of incident venous thrombosis in postmenopausal women.

Essentials Vasomotor symptoms have been proposed as markers of changing cardiovascular risk. In this cohort study, we evaluated these symptoms as markers of venous thrombosis (VT) risk. We found no evidence that vasomotor symptom presence or severity were associated with VT risk. Among these postmenopausal women, vasomotor symptoms are not a useful marker of VT risk. SUMMARY: Background Vasomotor symptoms may be markers of changes in cardiovascular risk, but it is unknown whether these symptoms are associated with the risk of venous thrombosis (VT). Objective To evaluate the association of vasomotor symptom presence and severity with incident VT risk among postmenopausal women, independent of potential explanatory variables. Methods This cohort study included participants of the Women's Health Initiative (WHI) Hormone Therapy Trials (n = 24 508) and Observational Study (n = 87 783), analyzed separately. At baseline, women reported whether hot flashes or night sweats were present and, if so, their severity. Using Cox proportional hazards models, we estimated the VT risk associated with vasomotor symptom presence and severity, adjusted for potential explanatory variables: age, body mass index, smoking status, race/ethnicity, and time-varying current hormone therapy use. Results At baseline, WHI Hormone Therapy Trial participants were aged 64 years and WHI Observational Study participants were aged 63 years, on average. In the WHI Hormone Therapy Trials over a median of 8.2 years of follow-up, 522 women experienced a VT event. In the WHI Observational Study, over 7.9 years of follow-up, 1103 women experienced a VT event. In adjusted analyses, we found no evidence of an association between vasomotor symptom presence (hazard ratio [HR]adj  0.91, 95% confidence interval [CI] 0.75-1.1 in the WHI Hormone Therapy Trials; HRadj  1.1, 95% CI 0.99-1.3 in the WHI Observational Study) or severity (HRadj for severe versus mild 0.99, 95% CI 0.53-1.9 in the WHI Hormone Therapy Trials; HRadj  1.3, 95% CI 0.89-2.0) in the WHI Observational Study) and the risk of incident VT. Conclusions Although vasomotor symptoms have been associated with the risk of other cardiovascular events in published studies, our findings do not suggest that vasomotor symptoms constitute a marker of VT risk.

Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women.

Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation. SUMMARY: Background Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 µg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

Daily salivary cortisol patterns in midlife women with hot flashes.

OBJECTIVE: Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes are associated with aberrant cortisol patterns similar to sleep-deficient individuals. DESIGN: Cross-sectional. PARTICIPANTS: A total of 306 women, ages 40-62, randomized to a behavioural intervention for hot flashes. MEASUREMENTS: Baseline comparisons of cortisol geometric means (nmol/l) from four daily time points averaged over two consecutive days plus other calculated cortisol measures were made between groups defined by baseline: (i) mean daily hot flash frequency tertile (≤5·5, N = 103; >5·5-8·8, N = 103; >8·8, N = 100) and (ii) selected characteristics. Repeated-measures linear regression models of log-transformed cortisol evaluated group differences, adjusting for covariates. RESULTS: Women were 67% White and 24% African American, with 7·6 (SD 3·9) hot flashes per day. Salivary cortisol geometric means (nmol/l) among all women were as follows: 75·0 (SD 44·8) total, 8·6 (SD 5·6) wake, 10·0 (SD 7·5) wake +30 min, 3·7 (SD 3·3) early afternoon and 1·6 (SD 1·8) bedtime. Wake + 30-minute values showed an 18% median rise from wake values (interquartile range -24 to 96%), and means varied by hot flash frequency tertile, from lowest to highest: 11·4(SD 7·3), 10·3 (SD 6·5) and 8·6 (SD 7·8), respectively, P = 0·003. Beside the early afternoon value (P = 0·02), cortisol values did not vary by hot flash frequency. CONCLUSION: Taken together, these findings suggest that high frequency of moderate-to-severe hot flashes may be associated with subtle abnormalities in cortisol concentrations - a pattern consistent with chronic sleep disturbance.

MsFLASH participants' priorities for alleviating menopausal symptoms.

OBJECTIVE: To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). METHODS: Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires. RESULTS: The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom. CONCLUSIONS: Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research.

Hot flush severity during the menopausal transition and early postmenopause: beyond hormones.

BACKGROUND: Understanding factors promoting symptom severity is essential to developing innovative symptom management models. AIM: To investigate hot flush severity during the menopausal transition (MT) and early postmenopause and effects of age, MT stages, age of onset of late stage and final menstrual period (FMP), estrogen, follicle stimulating hormone (FSH), cortisol, anxiety, perceived stress, body mass index, smoking, alcohol use and exercise. METHODS: A subset of participants in the Seattle Midlife Women's Health Study (n = 291 with up to 6973 observations) provided data during the late reproductive, early and late MT stages and early postmenopause, including menstrual calendars, annual health questionnaires, and symptom diaries and urine specimens assayed for hormones several times per year. Multilevel modeling with an R program was used to test models accounting for hot flush severity. RESULTS: Hot flush severity persisted through the MT stages and peaked during the late MT stage, diminishing after the second year postmenopause. In individual analyses, hot flush severity was associated with being older, being in the late MT stage or early postmenopause, beginning the late MT stage at a younger age and reporting greater anxiety. In a model including only endocrine factors, hot flush severity was significantly associated with higher FSH and lower estrone levels. An integrated model revealed dominant effects of late MT stage and early postmenopause, with anxiety contributing to hot flush severity. CONCLUSIONS AND IMPLICATIONS: Hot flush severity was affected largely by reproductive aging and anxiety, suggesting symptom management models that modulate anxiety and enhance women's experience of the menopausal transition and early postmenopause.

Effects of herbal preparations on symptom clusters during the menopausal transition.

AIMS: To determine the effects of herbal therapies on hot flushes and at least one other symptom including, sleep, mood, cognition, and pain that women experience during the menopausal transition and early postmenopause. METHODS: An extensive search of 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 randomized, controlled trials reported in English between January 2004 and July was conducted by an experienced reference librarian. There were 1193 abstracts identified but only 58 trials examined effectiveness of therapies for hot flushes and at least one additional co-occurring symptom. RESULTS: Seventeen studies used herbal preparation including seven studies of black cohosh, two studies of black cohosh mixed with other herbals, and eight studies of other herbals. Of these, one study of black cohosh, two studies of black cohosh mixed with other herbals, and four other herbal studies had significant effects on hot flushes and at least one additional co-occurring symptom. The adverse events of herbal therapies were various, ranging from mild to moderate and women were generally tolerant of the preparations. CONCLUSIONS: Black cohosh mixed with other herbals, Rheum rhaponticum, and French maritime pine bark had significant effects on hot flushes and at least one other symptom. These herbal therapies may be a promising alternative treatment to hormonal treatment. Future studies should classify women based on their menopausal stages, report each symptom separately, have adequate sample size, focus on multiple co-occurring symptoms, and target symptom management of menopausal symptoms.

Effects of traditional Chinese medicine on symptom clusters during the menopausal transition.

AIMS: To review controlled clinical trials of traditional Chinese medicine (TCM) therapies for hot flushes and at least one other co-occurring symptom among sleep, cognitive function, mood, and pain. METHODS: An experienced reference librarian performed an extensive search of 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 randomized, controlled trials reported in English between 2004 and July 2011. Of 1193 abstracts identified, 58 trials examined effectiveness of therapies for hot flushes and at least one additional co-occurring symptom. RESULTS: Eleven trials (13 publications) examined TCM therapeutics of acupuncture, Chinese herbal medicine (CHM) or moxibustion. Acupuncture trials (eight) yielded mixed results; five trials significantly reduced hot flushes. Of those five trials, one also showed benefit for sleep and pain and two trials found benefit for mood symptoms. Of three CHM trials, three trials had significant findings: one for hot flushes and mood, one for hot flushes and pain, and one for hot flushes, sleep, mood symptoms and pain. Moxibustion and counseling (one trial) significantly reduced hot flushes, mood symptoms and pain. None of the trials reported any serious adverse events. CONCLUSIONS: TCM therapeutics of acupuncture, CHM and moxibustion show promising results for the treatment of mood and pain symptoms co-occurring with hot flushes. Although the controlled clinical trials of TCM therapeutics reviewed here measured multiple symptom outcomes, few report treatment effects in ways that allow clinicians to consider symptom clusters when prescribing therapies. Future studies need to measure and report results for individual symptoms or group like symptoms together into subscales. Controlled clinical trials with larger numbers of participants are essential to allow evaluation of these therapies on hot flushes and multiple co-occurring symptoms.

Effects of mind-body therapies on symptom clusters during the menopausal transition.

AIMS: Although most women experience symptom clusters during the menopausal transition and early postmenopause, investigators reporting clinical trial effects for hot flushes often omit co-occurring symptoms. Our aim was to review controlled clinical trials of mind-body therapies for hot flushes and at least one other co-occurring symptom from these groups: sleep, cognitive function, mood, and pain. METHODS: An experienced reference librarian performed an extensive search of 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 randomized controlled trials reported in English between 2004 and July 2011. Of 1193 abstracts identified, 58 trials examining effectiveness of therapies for hot flushes and at least one additional co-occurring symptom of interest were identified. RESULTS: Eight trials (ten publications) examined relaxation, yoga, or exercise. Physical activity/exercise trials (six) yielded mixed results; only one significantly reduced hot flushes and mood symptoms. Of two relaxation therapy trials, only mindfulness-based stress reduction training reduced sleep and mood symptoms and had within-group treatment effects on hot flushes. Yoga (one trial) significantly reduced hot flushes and improved cognitive symptoms more than exercise, and also had within-group effects on sleep and pain symptoms. CONCLUSIONS: Studies of mind-body therapies for hot flushes increasingly measure multiple symptom outcomes, but few report treatment effects in ways that allow clinicians to consider symptom clusters when prescribing therapies. Future studies need to measure and report results for individual symptoms or group like symptoms together into subscales rather than use subscales with mixed dimensions. Trials with larger numbers of participants are essential to allow evaluation of these therapies on multiple co-occurring symptoms.

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

BACKGROUND: Urinary incontinence (UI) becomes more prevalent as women age, but little is known about UI in midlife, including stress incontinence (SUI) and urge incontinence (UUI) and their relationship to reproductive aging, reproductive history, health-related factors, and personal and social factors associated with midlife. OBJECTIVES: To determine the influence of age and reproductive aging factors (menopausal transition stages, follicle stimulating hormone (FSH), estrone glucoronide), reproductive history (number of live births), health-related factors (perceived health, body mass index (BMI), exercise, diabetes) and personal and social factors (race/ethnicity, education) on the experience of UI among midlife women during the menopausal transition and early postmenopause. METHODS: A subset of the Seattle Midlife Women's Health Study participants (n = 298 with up to 2249 observations) provided data during the late reproductive, early and late menopausal transition stages and early postmenopause, including menstrual calendars, annual health questionnaire and provided health diaries since 1990. Generalized estimating equation analysis was used to test models accounting for SUI and UUI that included age as a measure of time with predictors. RESULTS: Stress urinary incontinence was associated significantly with individual predictors of: worse perceived health (odds ratio (OR) 0.89, p = 0.025), history of ≥ three live births (OR 3.00, p = 0.002), being in the early menopausal transition stage (OR 1.53, p = 0.06), having less formal education (OR 0.33, p = 0.02), and being White/not Black (OR 0.32, p = 0.04). The most parsimonious model for SUI included: worse perceived health, ≥ three live births, and being White. Urge incontinence was associated significantly with individual predictors of: increasing age (OR 1.06, p = 0.001), worse perceived health (OR 0.78, p < 0.001), BMI ≥ 30 kg/m(2) (OR 2.96, p = 0.001), history of ≥ three live births (OR 2.81, p = 0.01), and lower FSH levels (OR 0.59, p = 0.08). The most parsimonious model for UUI included: being older, having worse perceived health, and having a high BMI. CONCLUSIONS: SUI risk was a function of reproductive history, poor health, and being White. UUI risk was a function of aging, having worse health, and higher BMI. Further exploration of UI during the menopausal transition is needed to articulate a lifespan view of UI and its typology.

Identifying symptom clusters during the menopausal transition: observations from the Seattle Midlife Women's Health Study.

OBJECTIVES: First, to explore the variability in how symptoms clustered together over the late reproductive stage, early and late menopausal transition (MT) stages, and early postmenopause; second, to determine whether the symptom factor structure of the preceding MT stage would predict the symptom factor structure of the MT stage immediately following. METHODS: The sample consisted of a subset of Seattle Midlife Women's Health Study participants who were in late reproductive or early or late menopausal transition stages or early postmenopause and provided self-reported data on symptoms experienced between 1990 and 2005. Principal components analysis was used to determine how symptoms clustered together across the stages. Variables predicting the symptom factor structure were analyzed by multiple regression. RESULTS: Principal components analysis with varimax rotation revealed different factor structures for each of the four stages. The three-factor solution in the late reproductive stage explained a total of 54.9% of the variance. The four-factor solutions in the early and late menopausal transition stages and postmenopause explained a total of 56.5%, 59.3%, and 60.7%, respectively. CONCLUSIONS: 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.

Cognitive symptoms during the menopausal transition and early postmenopause.

PURPOSES: To describe changes in levels of cognitive symptoms (forgetting and difficulty concentrating) during the menopausal transition (MT) stages and early postmenopause, including effects of age, MT-related factors(MT stages, estrone, follicle stimulating hormone (FSH), testosterone), symptoms (hot flush, sleep, mood), health-related factors (alcohol use, smoking, exercise, perceived health), stress-related factors (perceived stress, history of sexual abuse, cortisol, catecholamines) and social factors (partner and parenting status, education, employment). METHODS: A subset was studied of Seattle Midlife Women's Health Study participants who provided data during the late reproductive, early and late MT stages or postmenopause (n=292) including menstrual calendars for staging the MT, annual health questionnaires for social factors, morning urine samples assayed for estrone glucuronide (E1G), testosterone, FSH, cortisol and catecholamines and health diaries for rating symptoms several times each year. Multilevel modeling (R program) was used to test patterns of cognitive symptoms related to age, MT-related factors, symptoms, health-related, stress-related and social factors with as many as 6811 observations. RESULTS: As individual covariates and in the multivariate model, age, anxiety, depressed mood, night-time awakening, perceived stress, perceived health, and employment were each significantly related to difficulty concentrating. Hot flushes, amount of exercise and history of sexual abuse had a significant effect as individual covariates but not in the final multivariate model. The best predictors of forgetfulness when analyzed as individual covariates and in the multivariate model were age, hot flushes, anxiety, depressed mood, perceived stress, perceived health and history of sexual abuse. Awakening during the night, although significant as an individual covariate, had no significant effect on forgetfulness in the final multivariate model. CONCLUSIONS: Menopausal transition-related factors were not significantly associated with difficulty concentrating or forgetfulness. Consideration of women's ages and the context in which they experience the menopausal transition may be helpful in understanding women's experiences of cognitive symptoms.

Pain symptoms during the menopausal transition and early postmenopause.

AIM: The aim of this study was to describe changes in levels of back pain and joint pain during the stages of menopausal transition stages and early postmenopause, including the effects of age, menopausal transition-related factors (estrone, follicle stimulating hormone (FSH), testosterone), menopausal transition stages, symptoms (hot flush, sleep, mood, cognitive), health-related factors (body mass index, alcohol use, smoking, well-being), stress-related factors (perceived stress, history of sexual abuse, cortisol, catecholamines) and social factors (partner and parenting status, education). METHODS: A subset was studied of the participants in the Seattle Midlife Women's Health Study who provided data during the late reproductive, early and late menopausal transition stages or postmenopause (n = 292) including menstrual calendars for staging the menopausal transition, annual health reports completed between 1990 and 2006, and morning urine samples assayed for estrone glucuronide (E(1)G), testosterone, FSH, cortisol and catecholamines, and symptom diary ratings several times each year. Multilevel modeling with an R program was used to test patterns of pain symptoms related to age, menopausal transition-related factors, symptoms, health-related, stress-related and social factors, with as many as 6812 observations. Age was centered at 47.4 years. RESULTS: Women experienced a slight, non-significant rise in back pain with age and a significant increase in back pain during the early (p = 0.003) and late menopausal transition stages (p = 0.002) and early postmenopause (p = 0.02), but urinary E(1)G, FSH and testosterone levels were unrelated. Of the stress-related factors, perceived stress (p = 0.01) and lower overnight urinary cortisol levels were associated with more severe back pain (p = 0.03); history of sexual abuse and catecholamines did not have a significant effect. Those most troubled by symptoms of hot flushes, depressed mood, anxiety, night-time awakening, and difficulty concentrating reported significantly greater back pain (all p < 0.0001). Of the health-related factors, having worse perceived health (p < 0.0001), exercising more (p = 0.005), using analgesics (p < 0.0001), and having a higher body mass index (p < 0.0001) were associated with more back pain, but alcohol use and smoking did not have significant effects. Of the social factors, only having a more formal education (p = 0.004) was associated with less back pain; parenting, having a partner, and employment were not significant. Factors associated with joint pain included age (p < 0.0001), but not menopausal transition-related factors. Symptoms of hot flushes, night-time awakening, depressed mood, and difficulty concentrating were each significantly associated with joint pain (p < 0.0001). Poorer perceived health, more exercise, higher body mass index, and greater analgesic use were all associated similarly with joint pain. History of sexual abuse was the only stress-related factor significantly related to joint pain severity (p = 0.024). IMPLICATIONS: Clinicians working with women traversing the menopausal transition should be aware that managing back and joint pain symptoms among mid-life women requires consideration of their changing biology as well as their ongoing life challenges and health-related behaviors.

Midlife women making hormone therapy decisions.

This study focuses on midlife women aged 40-65 years who were in transition to menopause, were menopausal or had a hysterectomy, to examine and better understand hormone therapy (HT) choices women make. Among the nationally representative sample of women in the Commonwealth Fund 1998 Survey of Women's Health (n = 884), 39% of the menopausal women reported current HT use. The two primary reasons for initiating HT are following a doctor's recommendation and seeking relief of menopausal symptoms. Age, education, race, hysterectomy status, having health insurance, use of calcium supplements and comfort in communicating with a doctor are important factors associated with HT use. This study underscores the importance of physicians and other health professionals providing accurate HT information to assist women in making HT decisions.

Three stages of the menopausal transition from the Seattle Midlife Women's Health Study: toward a more precise definition.

OBJECTIVES: As more interest centers on the years surrounding menopause, the inconsistent use of nonspecific terminology to define these years becomes a problem. Our objective was to describe the development of specific criteria that define stages within the menopausal transition and to apply these criteria to classify midlife women into a stage of transition. DESIGN: A total of 184 midlife women from the Seattle Midlife Women's Health Study taking no hormones and for whom data were available about initial menstrual cycle changes were studied. Questionnaires about menstrual cycle changes and menstrual calendars were mailed yearly. Intra-individual analyses for type and chronology of menstrual cycle changes during midlife for change in flow amount or duration, cycle length change, cycle irregularity, or skipped periods were conducted. RESULTS: Changes in flow or cycle length most frequently preceded irregularity without skipped periods, which preceded skipped periods. Initial changes began in the early 30s and most frequently between ages 40 and 44. Only 14% had irregularity as the initial change. Three stages of the menopausal transition were identified: early (flow and/or cycle length changes), middle (irregularity without skipping), and late (skipped periods). Age did not differentiate the three stages. CONCLUSIONS: These findings provide evidence for a progression of menstrual cycle events through the menopausal transition, which form the basis for three stages of the transition: early, middle, and late transition. Studies about the entire transition need to include women younger than 45. Both menstrual calendars and questionnaire data are needed to identify these three stages, and precise definitions of irregularity and skipped period are necessary.

Changes in LDL density across the menopausal transition.

BACKGROUND: The risk of coronary artery disease increases in women after menopause. This increased risk may be associated with alterations in the lipid profile characterized by changes in LDL particle size and buoyancy. Characterization of lipoprotein levels and LDL buoyancy across the stages of the menopausal transition has yet to be reported. METHODS: Plasma lipoprotein concentrations, LDL buoyancy, and body mass index (BMI) were studied cross-sectionally in five groups of women: premenopausal women (n = 42), women in early menopausal transition (n = 35), middle menopausal transition (n = 19), late menopausal transition (n = 20), and postmenopausal women (n = 14). No women were taking estrogen. RESULTS: The postmenopausal women had significantly higher low-density lipoprotein cholesterol (LDL-C) and total cholesterol than premenopausal women (P < 0.05). LDL-C and Apo B was significantly higher in women in the late menopausal transition compared to premenopausal women (P < 0.05). All women in the menopausal transition and postmenopause had significantly more dense LDL than premenopausal women (P < 0.05). Multiple regression analysis revealed that the change in LDL buoyancy associated with the menopausal transition period could be explained by changes in triglyceride and HDL-C, related to changes in body mass index. CONCLUSIONS: These data suggest that the menopausal transition is associated with more dense LDL and higher LDL-C levels in comparison to premenopausal women. It appears that whereas LDL-C may change late in the menopausal transition, the production of denser LDL particles appears early in the menopausal transition, both acting to worsen the lipoprotein profile. Increased triglyceride and decreased HDL appeared to account for the shift toward small, dense LDL, presumably related to increased BMI. The change in LDL density may contribute to the higher incidence of atherosclerosis in postmenopausal women.

Memory functioning among midlife women: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: As the number of midlife women increases, there is an increased interest in women's experiences of the perimenopause. Because of the evidence linking estrogen with cholinergic and serotonergic activity in the brain and with central nervous system development of dendritic arborization, and mixed evidence of estrogen use with incidence of Alzheimer's disease, the effects of the perimenopause on memory functioning are of interest. The purpose of these analyses, part of the Seattle Midlife Women's Health Study, was to describe changes in women's perceived memory functioning according to their perimenopausal group, age, perceived stress, health status, and mood. DESIGN: Memory functioning was assessed with the Memory Functioning Questionnaire as part of a questionnaire mailed to study participants annually. Perimenopausal group was assessed using Mitchell's rating schema. RESULTS: Age was unrelated to any of the Memory Functioning Questionnaire indicators except for retrospective memory; younger women reported more memory problems than older women. Perimenopausal groups were unrelated to most memory functioning ratings with few exceptions. Memory functioning ratings of current memory compared with the past were worse for women who were in early and middle transition and for those who were using hormone therapy than for those who were in late transition and postmenopause. Women reported more current memory problems compared with 10 and 20 years ago and at age 18. Health ratings were negatively correlated with memory functioning ratings, and depressed mood positively correlated with nearly every indicator of memory functioning (frequency of memory problems, ratings of current memory, past memory, and memory change). Greater perceived stress levels were associated with more memory problems. CONCLUSIONS: Perceived memory functioning seems more closely related to perceived health, depressed mood, and perceived stress than to perimenopausal stage or age. Further work is needed to determine whether these ratings provided by the Seattle cohort will change over time as women age and as they make the transition to menopause and beyond.

The North American Menopause Society 1998 menopause survey: Part II. Counseling about hormone replacement therapy: association with socioeconomic status and access to medical care.

OBJECTIVE: The purpose of this study was to examine two predictors of women's obtaining hormone replacement therapy (HRT) counseling: socioeconomic status and access to health care. DESIGN: During May-July 1998, by means of random-digit telephone dialing, 749 postmenopausal women who were living in the United States and aged 50-65 years were interviewed. On average, they were 56.8 years and 11.8 years postmenopausal. Most (86.0%) were Caucasian, and their median annual income was approximately $40,000. Nearly all (90.8%) had medical insurance coverage; 47.6% of those insured received care from a managed care organization. Access to medical care was evidenced by 92.3% being under the care of a primary care physician, 92.3% ever having had a mammogram, 96.9% ever having had a pelvic examination, and 91.1% ever having had a serum cholesterol determination. RESULTS: Of these 749 women, 75.4% reported that they had received counseling about post-menopausal HRT from healthcare providers. Both level of education and level of income were associated with an increased likelihood that HRT counseling would be obtained. Having a personal physician, and particularly receiving care from a gynecologist, increased the likelihood that counseling would be available. There were no substantial differences in counseling frequency between women in managed care plans and those having other types of health insurance. In a multivariate model, adjusted odds ratios for receiving HRT counseling were 2.9 (95% confidence interval [CI] = 1.7-4.8) for having an annual income of $50,000 or more versus less than $30,000, 2.8 (95% CI = 1.7-4.5) for receiving care from a gynecologist versus other primary care physician, 1.9 (95% CI = 1.1-3.2) for being Caucasian versus not, and 1.5 (95% CI 1.0-2.2) for having a hysterectomy versus not. CONCLUSIONS: Three quarters of a sample of US postmenopausal women aged 50-65 years reported that they had been counseled about HRT. However, women of lowest socioeconomic status and those who did not have a primary care physician were least likely to have received counseling. No differences were observed in prevalence of counseling between women in managed care settings and those with other types of health insurance. The findings suggest that special efforts are necessary to provide menopause education and counseling to underserved women.

Bone resorption levels by age and menopausal status in 5,157 women.

OBJECTIVE: The purpose of this study was to describe bone resorption activity using a biochemical marker according to the categories of age, menopausal status, and selected drug/supplement use in middle-aged and elderly community-based women. DESIGN: This was a cross-sectional study that assessed urinary cross-linked N-telopeptide of type I collagen (NTx) and used self-report data to group women as premenopausal (Pre), perimenopausal (Peri), postmenopausal without hormone replacement therapy (Post), and postmenopausal with hormone replacement therapy (HRT). RESULTS: Mean NTx values were found to be significantly different by group and controlling for age (p = 0.001), with post hoc tests showing all pairwise group comparisons as significantly different (p = 0.001), except that the Pre and HRT groups were not significantly different. Both the Peri and the Post NTx levels were significantly higher than the Pre and the HRT groups'. NTx values in the Peri group varied with age-the youngest Peri women were similar to Pre women, and the oldest Peri women were similar to Post women. Significantly lower NTx levels were found only in the Post (p = 0.009) and HRT (p < 0.001) groups using diuretics compared with nonuse and only in the HRT group using calcium supplements compared with nonuse (p = 0.006). No differences by thyroid use were found. With a biochemical marker, the results showed that bone resorption activity differences could be demarcated in women according to age, estimated menopausal stage, and selected drug/supplement use. CONCLUSIONS: These results support the usefulness of NTx assessment for indicating bone resorption activity and therefore the potential for osteoporosis or for monitoring the efficacy of antiresorptive therapies.