Menopausal Transition Stage Research Articles

Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary and Recommendations.

There is a new appreciation of the perimenopause-defined as the early and late menopause transition stages as well as the early postmenopause-as a window of vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: (1) epidemiology; (2) clinical presentation; (3) therapeutic effects of antidepressants; (4) effects of hormone therapy; and (5) efficacy of other therapies (e.g., psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (i.e., vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (i.e., antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Constipation and diarrhea during the menopause transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

To assess the relationship of constipation and diarrhea severity during the menopause transition (MT) with age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions. From 1990 to 1992, women aged 35 to 55 years were recruited from the greater Seattle area; 291 of them consented to ongoing (1990-2013) annual data collection by daily menstrual calendar, health diary, and annual health questionnaire. A subset (n = 131) provided a first morning voided urine specimen (1997-2013). These were assayed for levels of E1G, follicle-stimulating hormone, testosterone, cortisol, norepinephrine, and epinephrine. Mixed-effects modeling was used to identify how changes in constipation and diarrhea severity over time related to age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions. In a univariate model, age, late reproductive (LR) stage, tension, and anxiety were all significantly and positively related to constipation severity, whereas cortisol was significantly and negatively associated. In a multivariate model, only tension and cortisol remained significant predictors of constipation severity (P < 0.05). In a univariate model, age, LR stage, and estrone glucuronide were significantly and negatively associated with diarrhea severity, whereas tension, anxiety, and perceived stress were significantly and positively related. In a multivariate model, only tension and age remained significant predictors of diarrhea severity. Key reproductive hormones do not play a significant role in constipation or diarrhea severity in the MT. In contrast, stress perception, tension, anxiety, and cortisol do. These factors should be evaluated in further research involving constipation and diarrhea.

Impact of Menopause on Quality of Life in Community-based Women in China: 1 Year Follow-up

Quality of life (QOL) throughout menopause has become an outcome variable requiring measurement in clinical care. Staff nurses can provide earlier nursing during the menopausal transition (MT) stage. The purpose of this study was to describe the changes of QOL in different stages of the MT according to The Stages of Reproductive Aging Workshop (STRAW) in Chinese women in community settings. Prospective longitudinal study design was used to analyze QOL of 327 community women age 30–65years old. They were followed up at 1-year. An instrument including the Chinese version of the Menopause-Specific Quality of Life Questionnaire was used to obtain data. A gradual decline in QOL was seen from premenopausal to menopausal transition (MT) and in postmenopausal women. Significant differences were observed in vasomotor, physical and sexual scores at baseline and follow-up (P<0.05). Significant differences in vasomotor scores were observed between baseline and follow-up for women in the premenopausal and Late MT stages (P<0.05). There were significant differences in psychosocial and physical scores between baseline and follow-up in the Late MT stage (P<0.05). Menopause might have a negative impact on QOL independent of age in community-based women in China. There seemed to be a potential model of the relationship of menopause status to change in QOL, but this needs supporting evidence from longer longitudinal studies.

Sleep During Menopausal Transition: A 6-Year Follow-Up.

Menopausal transition is associated with increased dissatisfaction with sleep, but the effects on sleep architecture are conflicting. This prospective 6-year follow-up study was designed to evaluate the changes in sleep stages and sleep continuity that occur in women during menopausal transition. Sixty women (mean age 46.0 years, SD 0.9) participated. All women were premenopausal at baseline, and at the 6-year follow-up, women were in different stages of menopausal transition. Polysomnography was used to study sleep architecture at baseline and follow-up. The effects of aging and menopause (assessed as change in serum follicle-stimulating hormone [S-FSH]) on sleep architecture were evaluated using linear regression models. After controlling for body mass index, vasomotor, and depressive symptoms, aging of 6 years resulted in shorter total sleep time (B -37.4, 95% confidence interval [CI] -71.5 to (-3.3)), lower sleep efficiency (B -6.5, 95%CI -12.7 to (-0.2)), as well as in increased transitions from slow-wave sleep (SWS) to wakefulness (B 1.0, 95%CI 0.1 to 1.9), wake after sleep onset (B 37.7, 95%CI 12.5 to 63.0), awakenings per hour (B 1.8, 95%CI 0.8 to 2.8), and arousal index (B 2.3, 95%CI 0.1 to 4.4). Higher S-FSH concentration in menopausal transition was associated with increased SWS (B 0.09, 95%CI 0.01 to 0.16) after controlling for confounding factors. A significant deterioration in sleep continuity occurs when women age from 46 to 52 years, but change from premenopausal to menopausal state restores some SWS.

Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms.

Vasomotor symptoms (VMS) may be associated with an increased risk of cardiovascular disease. One candidate mechanism may involve alterations in physiological responses to stress. The current study therefore examined the relationship between self-reported VMS bother and cardiovascular, hemodynamic, neuroendocrine, and inflammatory responses to an acute psychosocial stress protocol. One hundred eighty-six women in the menopausal transition or early postmenopausal stage (age 45-60 y) provided the data for this article. Subjective hot flash and night sweat bother were assessed using the Greene Climacteric Scale. Women also underwent a stressor battery involving a speech and a mental arithmetic task while cardiovascular, hemodynamic, neuroendocrine, and inflammatory responses were assessed. Repeated measures regression analyses were used to examine the relationship between self-reported VMS and physiologic responses to the stressor. In multivariate analyses adjusting for potential confounders, self-reported hot flash bother was associated with lower overall cardiac index and stroke volume index and higher overall vascular resistance index and levels of the inflammatory cytokine interleukin-6. Hot flash bother also tended to be associated with higher overall cortisol levels and higher baseline levels of plasma norepinephrine. Night sweat bother, on the other hand, was associated with higher overall cortisol levels and tended to be associated with higher interleukin-6. Self-reported VMS bother is associated with an unfavorable hemodynamic and neuroendocrine profile characterized by increased hypothalamic-pituitary-adrenal axis and central sympathetic activation, inflammation, and vasoconstriction. Further research investigating this profile in relation to VMS, and the potential health implications of this association, is warranted.

“Adopting self-sacrifice”: how Iranian women cope with the sexual problems during the menopausal transition? An exploratory qualitative study

Objective: In the menopausal transition sexual problems are an important issue and one of the most frequently presented health concerns of women attending menopause clinics. This study aimed to explore the ways of managing sexual dysfunctions during the menopausal transition among Iranian women.Methods: This exploratory qualitative study was conducted in Iran, from May 2013 to April 2015. Twenty-one women in three stages of menopausal transition, aged 42–55 years old, were purposively selected from urban health centers in Mashhad and Gonabad, Iran. Semi-structured in depth interviews were conducted for data collection until data saturation was achieved. All interviews were recorded electronically and transcribed verbatim. Conventional content analysis was used for data analysis using Granehiem and Lundman (2004) recommended method. MAXQDA 2007 software was used for organizing data and managing the process of analysis.Results: Data analysis demonstrated one overarching theme entitled “Adopting self-sacrifice” consisting of three categories and seven sub-categories. Major categories included: (1) Confronting decline of libido with two subcategories of women’s libido decline and inability to fulfill husbands’ sexual needs, (2) Seeking strategies for coping with two subcategories of looking for experiences of peer menopausal women and choosing how to interact with the husband and (3) Achieving problem solving strategies with three sub-categories of obedience in sexual relationships (Tamkin), employing affection based on religious advice, and giving up own right to reach mutual understanding.Conclusions: The major finding of this study was “Adopting self-sacrifice” in the process of managing sexual dysfunctions during the menopausal transition. The reason for choosing this passive approach by the majority of women has deep roots in their cultural and traditional beliefs.

Metabolic and hormone influences on emotion processing during menopause

Disturbances of emotion regulation and depressive symptoms are common during the menopause transition. Reproductive hormone levels are not directly correlated with depressive symptoms, and other factors may influence mood symptoms during menopause. In this study, we sought to determine the role of metabolic function in mood symptoms during menopause, hypothesizing an association with menopause status and long-term glucose load. We studied 54 women across three menopause transition stages (15 premenopause, 11 perimenopause, and 28 postmenopause), examining effects of age, hormones, and metabolism on mood and neural activation during emotional discrimination. We assessed participants using behavioral and functional MRI measures of negative emotion and emotion discrimination, and glycated hemoglobin A1c, to assess long-term glucose load. We found that emotionally unpleasant images activated emotion regulation (amygdala) and cognitive association brain regions (prefrontal cortex, posterior cingulate, temporal-parietal-occipital (TPO) junction, hippocampus). Cognitive association region activity increased with menopause stage. Perimenopausal women had left TPO junction activation, and postmenopausal women had prefrontal cortex, posterior cingulate, and TPO junction activation. Negative affect was associated with decreased amygdala activation, while depression symptoms and negative mood were associated with increased TPO junction activation. Hemoglobin A1c was associated with negative interpretation bias of neutral images and cognitive region recruitment during emotion discrimination. FSH levels, indicating menopause stage, were associated with negative mood. Age was not associated with any behavioral measures or activation patterns during the emotion task. Our results suggest that an interaction between metabolic and hormonal factors may influence emotion regulation, leading to increased risk for depression during menopause.

Depressive symptoms in midlife: the role of reproductive stage.

The aim of the study was to determine the prevalence of depression among community-dwelling women in the premenopause, menopausal transition (MT), and postmenopause stage. We also sought to clarify the direct and indirect contribution of menopausal status on the risk of depression. Cross-sectional survey of 1,612 women aged 45 to 55 years living in the Perth metropolitan region, who were recruited using a random sample of the electoral roll (voting is compulsory in Australia), was conducted. Women with clinically significant symptoms of depression had Patient Health Questionnaire (PHQ-9) scores of at least 10, and those with major depression, reported symptoms consistent with Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5), criteria. We used past and current gynecological and reproductive data to classify women as premenopausal, undergoing the MT, and postmenopausal. Other study measures included age, place of birth, education, marital status, drinking habit, number of children, medical illnesses, and history of premenstrual syndrome, postnatal depression, and past depression or anxiety. We investigated the direct and indirect effect of reproductive status with mediation/modulation analysis. Among the women included in the survey, 8.2%, 11.5%, and 13.0% of women in premenopause, MT, and postmenopause had PHQ-9 at least 10, whereas major depression was present in 2.2%, 3.4%, and 3.6% of them. Reproductive status did not affect the prevalence of major depression, but more postmenopausal than premenopausal women had PHQ-9 score equal to or greater than 10 (P = 0.013). Compared with premenopausal women, MT was associated with a direct odds ratio (OR) 1.35 (95% confidence interval [CI] = 0.90, 2.01) and indirect OR 1.08 (95% CI = 0.92, 1.26) for PHQ-9 at least 10. Similarly, the direct and indirect effect of the postmenopause on the odds of PHQ-9 at least 10 was OR 1.31 (95% CI = 0.87, 1.98) and OR 1.29 (95% CI = 1.10, 1.52). The slight, but not significant, excess of depressive symptoms during MT and early postmenopause cannot be attributed to a direct effect of reproductive status.

Menopausal Symptoms and Sleep Quality During Menopausal Transition and Postmenopause.

Background:Menopausal symptoms and sleep difficulty were physiological processes that were affected by genetic and other factors. This study was to investigate the prevalence of menopausal symptoms and sleep quality in menopausal transition (MT) and postmenopause (PM) women in Taiyuan, Shanxi.Methods:A community-based survey of women's menopausal symptoms and sleep quality was conducted between July 2012 and May 2013 at six municipal districts of Taiyuan, Shanxi. A sample of 2429 women aged 40–59 years was divided into four groups: early MT, late MT, early PM, and late PM. Sleep quality in the past 2 weeks before the interview was recorded. The data were analyzed using SPSS 16.0.Results:The prevalence of menopausal symptoms was 49.8%. Mild, moderate, and severe symptoms were observed in 28.9%, 18.5%, and 2.5% of participants, respectively. The highest prevalence of menopausal symptoms occurred in the early postmenopausal stage; the subsequences were the late postmenopausal stage and the early MT stage. Interestingly, among the 13 items of modified Kupperman index, the five most common symptoms were fatigue, arthralgia and myalgia, decreased libido, insomnia, and nervousness. Meanwhile, 55% perimenopausal women had poor sleep.Conclusions:Menopausal symptoms are common but mild among women in Taiyuan, Shanxi during MT and PM. In these stages, the prevalence of poor sleep is high.

Perimenopause and Menopause Are Associated With High Frequency Headache in Women With Migraine: Results of the American Migraine Prevalence and Prevention Study.

To examine the relationship of headache frequency to the stages of the menopausal transition in mid-life women with migraine. Past studies suggest that the perimenopause is associated with an increased prevalence of migraine, particularly in those with a history of premenstrual syndrome. The effect of the menopausal transition on the frequency of headache attacks in women with migraine has not been explored. This was a cross-sectional observational study. Using data from the 2006 American Migraine, Prevalence and Prevention study survey, women meeting modified ICHD-3 beta criteria for migraine between the ages of 35-65 years were included in analyses. Women who had never menstruated or were pregnant, breastfeeding, or using exogenous sex hormones were excluded. The 2006 survey was selected because it included detailed questions on the menstrual cycle. The stages of the menopausal transition were defined based upon the self-reported cycle length and/or duration of amenorrhea. The primary outcome, high vs low headache frequency, was defined using a cut score of ≥10 headache days per month. Binary logistic regression models were used to assess the influence of menopausal stage on headache frequency category using premenopause as the reference group. Adjustments for stage of menopausal transition and sociodemographics (eg, age and income) were included in the first model, while the second model included sociodemographics, depression, body mass index, preventative medications, and medication overuse. The study sample included 3664 women at a mean age of 46 years. Among women who were premenopausal, 8.0% (99/1242) were in the high frequency headache group in comparison with 12.2% (154/1266) of perimenopausal and 12.0% (131/1095) of postmenopausal women. Compared with premenopausal women, the adjusted odds of being in the high frequency headache group was 1.62 (95% CI = 1.23, 2.12) for perimenopausal and 1.76 (95% CI = 1.23, 2.52) for postmenopausal women (Model 1). In model 2, high frequency headache was only increased in perimenopausal women with an OR of 1.42 (95% CI = 1.03, 1.94). The risk of high frequency headache is increased in women during the perimenopause compared to premenopause in the fully adjusted model. The fact that the increased risk of high frequency headache was not statistically significant for menopause in the fully adjusted models suggests that different mechanisms might account for the increased risk for this stage of the menopausal transition. Recognition of the increased risk of high frequency headache during the menopausal transition suggests a need for optimized preventive treatment of migraine during this time of women's life.

Increase in circulating sclerostin at the early stage of menopausal transition in Japanese women

ObjectiveWe examined the change in circulating sclerostin level during the menopausal transition and we investigated the associations of sclerositin with hormones and bone turnover markers according to each menopausal stage in cross-sectional and longitudinal studies. MethodsWe conducted a cross-sectional study in 200 healthy Japanese women and divided them into 4 stages (reproductive, menopausal transition, early postmenopause and late postmenopause) by menstrual regularity, follicle-stimulating hormone level and years since menopause. Serum levels of sclerostin, bone turnover markers and reproductive hormones were measured. In addition, we examined changes in sclerostin level from the reproductive stage to menopausal transition and from menopausal transition to early postmenopause in a longitudinal study. ResultsIn the cross-sectional study, sclerostin level gradually increased with progression of menopausal stages and showed a significant change during the menopausal transition. Sclerostin levels significantly increased from the reproductive stage to menopausal transition and from menopausal transition to early postmenopause in the longitudinal study. A negative correlation of sclerostin with estradiol was found in early postmenopause. Sclerostin levels were negatively correlated with bone-specific alkaline phosphatase levels in the reproductive stage and menopausal transition and with tartrate-resistant acid phosphatase-5b in menopausal transition. ConclusionThe change in sclerostin has already occurred in the early stage of menopausal transition and sclerostin level increases with progression of menopausal stages. Elevated sclerostin levels during the menopausal transition may be involved in relative decline in bone formation against increase in bone resorption.

Sleep and menopause: a narrative review.

Our overall aim-through a narrative review-is to critically profile key extant evidence of menopause-related sleep, mostly from studies published in the last decade. We searched the database PubMed using selected Medical Subject Headings for sleep and menopause (n = 588 articles). Using similar headings, we also searched the Cochrane Library (n = 1), Embase (n = 449), Cumulative Index to Nursing and Allied Health Literature (n = 163), Web of Science (n = 506), and PsycINFO (n = 58). Articles deemed most related to the purpose were reviewed. Results were articulated with interpretive comments according to evidence of sleep quality (self-reported) and sleep patterns (polysomnography and actigraphy) impact as related to reproductive aging and in the context of vasomotor symptoms (VMS; self-reported), vasomotor activity (VMA) events (recorded skin conductance), depressed mood, and ovarian hormones. Predominantly, the menopausal transition conveys poor sleep beyond anticipated age effects. Perceptions of sleep are not necessarily translatable from detectable physical sleep changes and are probably affected by an emotional overlay on symptoms reporting. Sleep quality and pattern changes are mostly manifest in wakefulness indicators, but sleep pattern changes are not striking. Likely contributing are VMS of sufficient frequency/severity and bothersomeness, probably with a sweating component. VMA events influence physical sleep fragmentation but not necessarily extensive sleep loss or sleep architecture changes. Lack of robust connections between perceived and recorded sleep (and VMA) could be influenced by inadequate detection. There is a need for studies of women in well-defined menopausal transition stages who have no sleep problems, accounting for sleep-related disorders, mood, and other symptoms, with attention to VMS dimensions, distribution of VMS during night and day, and advanced measurement of symptoms and physiologic manifestations.

Insomnia in women approaching menopause: Beyond perception

The menopausal transition is marked by increased prevalence in disturbed sleep and insomnia, present in 40–60% of women, but evidence for a physiological basis for their sleep complaints is lacking. We aimed to quantify sleep disturbance and the underlying contribution of objective hot flashes in 72 women (age range: 43–57 years) who had (38 women), compared to those who had not (34 women), developed clinical insomnia in association with the menopausal transition. Sleep quality was assessed with two weeks of sleep diaries and one laboratory polysomnographic (PSG) recording. In multiple regression models controlling for menopausal transition stage, menstrual cycle phase, depression symptoms, and presence of objective hot flashes, a diagnosis of insomnia predicted PSG-measured total sleep time (p<0.01), sleep efficiency (p=0.01) and wakefulness after sleep onset (WASO) (p=0.01). Women with insomnia had, on average, 43.5min less PSG-measured sleep time (p<0.001). There was little evidence of cortical EEG hyperarousal in insomniacs apart from elevated beta EEG power during REM sleep. Estradiol and follicle stimulating hormone levels were unrelated to beta EEG power but were associated with the frequency of hot flashes. Insomniacs were more likely to have physiological hot flashes, and the presence of hot flashes predicted the number of PSG-awakenings per hour of sleep (p=0.03). From diaries, women with insomnia reported more WASO (p=0.002), more night-to-night variability in WASO (p<0.002) and more hot flashes (p=0.012) compared with controls. Women who develop insomnia in the approach to menopause have a measurable sleep deficit, with almost 50% of the sample having less than 6h of sleep. Compromised sleep that develops in the context of the menopausal transition should be addressed, taking into account unique aspects of menopause like hot flashes, to avoid the known negative health consequences associated with insufficient sleep and insomnia in midlife women.

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.

Menopausal stages and serum lipid and lipoprotein abnormalities in middle-aged women

ObjectivesWhether menopausal stage is associated with abnormalities in serum lipid and lipoprotein profiles remains unclear; studies have been conducted mostly in Western populations. This study aimed to examine the prevalence of lipid and lipoprotein abnormalities by recently updated menopausal stages in middle-aged women. Study designThis study was cross-sectional analysis of 1553 women aged 44–56 years, who underwent a comprehensive health screening examination in the Kangbuk Samsung Hospital Total Healthcare Centers, Korea, during 2012–2013. Lipid and lipoprotein profiles including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipoprotein (a) (Lp(a)), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B) were assessed. Prevalence ratios and 95% confidence intervals for lipid and lipoprotein abnormalities were estimated by menopausal stages as defined by the 2011 Stages of Reproductive Aging Workshop+10 criteria. ResultsIncreased prevalence of lipid and lipoprotein abnormalities were observed across menopausal stages. The increased prevalence of high non-HDL-C was associated with the late menopausal transition and post-menopausal stages and was more pronounced in women with body mass index (BMI) <23kg/m2 than in those with BMI ≥23kg/m2 (P for interaction=0.006). Similarly, there was an interaction between BMI and menopausal stages in relation to high Apo B (P for interaction=0.05) and high Apo B/Apo A1 ratio (P for interaction=0.06). ConclusionsOur findings extend previous results and suggest that the increased prevalence of lipid and lipoprotein abnormalities was associated not only with the post-menopausal stage but also late menopausal transition period.

Adult bone strength of children from single-parent families: the Midlife in the United States Study.

Bone health may be negatively impacted by childhood socio-environmental circumstances. We examined the independent associations of single-parent childhood and parental death or divorce in childhood with adult bone strength indices. Longer exposure to a single-parent household in childhood was associated with lower bone strength in adulthood. Because peak bone mass is acquired during childhood, bone health may be negatively impacted by childhood socio-environmental disadvantage. The goal of this study was to determine whether being raised in a single-parent household is associated with lower bone strength in adulthood. Using dual-energy X-ray absorptiometry data from 708 participants (mean age 57 years) in the Midlife in the United States Biomarker Project, we examined the independent associations of composite indices of femoral neck bone strength relative to load (in three failure modes: compression, bending, and impact) in adulthood with the experience of single-parent childhood and parental death or divorce in childhood. After adjustment for gender, race, menopause transition stage, age, and body mass index, each additional year of single-parent childhood was associated with 0.02 to 0.03 SD lower indices of adult femoral neck strength. In those with 9-16 years of single-parent childhood, the compression strength index was 0.41 SD lower, bending strength index was 0.31 SD lower, and impact strength index was 0.25 SD lower (all p values < 0.05). In contrast, parental death or divorce during childhood was not by itself independently associated with adult bone strength indices. The magnitudes of these associations were unaltered by additional adjustment for lifestyle factors and socioeconomic status in childhood and adulthood. Independent of parental death or divorce, growing up in a single-parent household is associated with lower femoral neck bone strength in adulthood, and this association is not entirely explained by childhood or adult socioeconomic conditions or lifestyle choices.

Staging reproductive aging using Stages of Reproductive Aging Workshop + 10 in black urban African women in the Study of Women Entering and in Endocrine Transition.

There has been limited research on accurate staging of the menopausal transition in sub-Saharan African women. Our aim was to assess the usefulness of the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria in staging ovarian aging in black South African women, examining whether obesity has any effect on the menopausal transition. The study enrolled 702 women aged 40 to 60 years. STRAW + 10 criteria were used to categorize the stages of reproductive aging. The Menopause Rating Scale was used to measure the prevalence of vasomotor symptoms. Follicle-stimulating hormone (FSH) and estradiol levels were used as supportive criteria for staging. Human immunodeficiency virus status was assessed using a point-of-care method. Reported age at final menstrual period (FMP) was higher in women interviewed within 4 years of FMP (mean [SD], 49.0 [3.80] y) than in women interviewed 10 years or more after FMP (mean [SD], 42.0 [4.06] y; P < 0.0005). In women within 4 years of FMP, lower body mass index was associated with earlier age at FMP. FSH levels increased and estradiol levels decreased (P < 0.0005 for both trends) across seven staging groups. Human immunodeficiency virus status had no effect on menopause symptoms. Obesity (body mass index ≥35.0 kg/m) was associated with severe vasomotor symptoms. Reporting of age at FMP is unreliable in women interviewed 4 years or more after the event. STRAW + 10 seems accurate in staging reproductive aging, as confirmed by the strong association of FSH and estradiol levels with the menopausal transition stage. STRAW + 10 may be appropriate for use in resource-limited settings in the absence of biomarkers. Biocultural methods may be useful in assessing the menopausal transition in culturally diverse women.

Bone mineral density changes among women initiating proton pump inhibitors or H2 receptor antagonists: a SWAN cohort study.

Proton pump inhibitors (PPIs) have been associated with diminished bone mineral density (BMD) and an increased risk of fracture; however, prior studies have not yielded consistent results, and many have suboptimal ascertainment of both PPI use and BMD. We used data from the Study of Women's Health Across the Nation (SWAN), a multicenter, multi-ethnic, community-based longitudinal cohort study of women across the menopause transition to examine the association between annualized BMD changes and new use of PPIs. We compared changes in BMD in new PPI users with changes in BMD in new users of histamine 2 receptor antagonists (H2RAs) and with changes in BMD in subjects who did not use either class of medications. Mixed linear regression models included recognized risk factors for osteoporosis, including demographics, menopausal transition stage, body mass index (BMI), lifestyle factors, as well as comorbidities and concomitant medications. To provide further evidence for the validity of our analytic approach, we also examined the effects of hormone-replacement therapy (HT), a class of medications that should reduce bone loss, on changes in BMD as an internal positive control group. We identified 207 new users of PPIs, 185 new users of H2RAs, and 1,676 non-users. Study subjects had a mean age of 50 years and were followed for a median of 9.9 years. Adjusted models found no difference in the annualized BMD change at the lumbar spine, femoral neck, or total hip in PPI users compared with H2RA users or non-users. These results were robust to sensitivity analyses. BMD increased as expected in HT users, supporting the validity of our study design. These longitudinal analyses plus similar prior studies argue against an association between PPI use and BMD loss.

Bleeding patterns during the menopausal transition in the multi-ethnic Study of Women's Health Across the Nation (SWAN): a prospective cohort study.

Previous studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population. Prospective community-based cohort study. southeastern Michigan, northern California and Los Angeles, California. A total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women. Women completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan-Meier survival analysis and multivariable regression were used to analyse the data. Menses of 10+ days, spotting of 6+ days, heavy bleeding of 3+ days. At least three occurrences of menses 10+ days was reported by 77.7% (95% confidence interval [95% CI] 56.7-93.2), of 6+ days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+ days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+ days, 6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+ days of heavy bleeding. These data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.

Multisystem Dysregulation and Bone Strength: Findings From the Study of Midlife in the United States

Accumulated dysregulation across multiple physiological systems, or allostatic load (AL), has been proposed as the biological pathway from psychosocial adversity to poor health. The objective of the study was to examine whether AL, constructed using biomarkers and medication data from seven systems (sympathetic, parasympathetic, hypothalamic-pituitary-adrenal axis, cardiovascular regulation, inflammation, and lipid and glucose metabolism), is associated with lower bone strength in a national sample. This was a cross-sectional study. Seven hundred three community-dwelling men and women from the Study of Midlife in the United States participated in the study. Bone mineral density (BMD) was measured in the femoral neck and lumbar spine. Femoral neck BMD was combined with bone size and body size to create composite indices of femoral neck strength relative to load in three failure modes: compression, bending, and impact. In mixed-effects linear regression controlling for clustering within families and adjusted for age, gender, race/ethnicity, body mass index, menopausal transition stage, childhood socioeconomic status, adult finances, education level, and study center, each SD increment in AL score was associated with between 0.10 and 0.11 SD decrements in lumbar spine BMD and each of the three composite strength indices (all values of P < .05). Gender modified the association of AL only with femoral neck BMD; each SD increment in AL score was associated with 0.21 SD decrement in femoral neck BMD in men (P < .01) but not in women. Accumulation of dysregulation across systems was modestly associated with lower bone strength. This study adds to the accumulating evidence that multisystem dysregulation, or AL, predicts a variety of adverse health outcomes.