Sybil L. Crawford

Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups.

In recent years, research on menopausal symptomalogy has focused on identifying symptom groupings experienced by women as they progress from premenopausal to postmenopausal status. However, most of these studies have been conducted among Caucasian women from western cultures. This leaves open the question of whether the findings from these studies can be extended to women of other racial/ethnic groups or cultures. Furthermore, many of the previous studies have been conducted on relatively small samples. This paper addresses the diversity of the menopause experience by comparing symptom reporting in a large cross-sectional survey of women aged 40-55 years among racial/ethnic groups of women in the United States (Caucasian, African-American, Chinese, Japanese, and Hispanic). Evaluation of the extent to which symptoms group together and consistently relate to menopausal status across these five samples provides evidence for or against a universal menopausal syndrome. The specific research questions addressed in this paper are: (1) How does the factor structure of symptoms among mid-aged women compare across racial/ethnic groups? (2) Is symptom reporting related to race/ethnicity or menopausal status? and (3) Does the relation between menopausal status and symptoms vary across racial/ethnic groups? Analyses are based on 14,906 women who participated in the multi-ethnic, multi-race, multi-site study of mid-aged women called the Study of Womens Health Across the Nation (SWAN). Study participants completed a 15-min telephone or in-person interview that contained questions on a variety of health-related topics. Items of interest for these analyses include symptoms, menstrual history (to assess menopausal status), health status, and sociodemographics. Factor analysis results showed that across all five racial/ethnic groups, two consistent factors emerged; one consisting of clearly menopausal symptoms -- hot flashes and night sweats -- and the other consisting of psychological and psychosomatic symptoms. Results of regression analyses showed racial/ethnic differences in symptom reporting, as well as differences by menopausal status. Controlling for age, education, health, and economic strain, Caucasian women reported significantly more psychosomatic symptoms than other racial/ethnic groups. African-American women reported significantly more vasomotor symptoms. Perimenopausal women, hormone users, and women who had a surgical menopause reported significantly more vasomotor symptoms. All of these groups, plus postmenopausal women, reported significantly more vasomotor symptoms than premenopausal women. The pattern of results argues against a universal menopausal syndrome consisting of a variety of vasomotor and psychological symptoms.

Quality of Life Among Younger Women With Breast Cancer

PURPOSE To describe quality of life (QOL) of younger women 4 to 42 months after breast cancer diagnosis and to identify factors associated with impaired QOL. METHODS A total of 202 women diagnosed with stage I to III breast cancer at age 50 or younger from 4 to 42 months after breast cancer diagnosis previously completed a mailed survey. Global QOL; health-related QOL as measured by the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B); medical history; symptoms; days of work/activity missed after diagnosis; relationship, sexual, and body image problems; coping strategies; and feelings of preparedness were measured. RESULTS General aches and pains and unhappiness with appearance were reported by more than 70% of women. Hot flashes (P = .0007), pain with sexual intercourse (P = .02), and difficulty with bladder control (P = .002) all significantly increased with age. Global QOL was significantly lower than for a nonpatient sample of younger women (P < .0001). In general, few sociodemographic and medical factors were related to QOL. In multivariate analyses, days of work/usual activity missed immediately after diagnosis; relationship, sexual, or body image problems after diagnosis; and coping strategies were related to almost all QOL domains. Ongoing treatment, vaginal dryness, and feeling unprepared for the impact of breast cancer were related to some domains. CONCLUSION Younger breast cancer survivors are at risk for impaired QOL up to several years after diagnosis. Younger women, especially those at high risk for lower QOL, may need interventions that specifically target their needs related to menopausal symptoms and problems with relationships, sexual functioning, and body image. Preparing younger woman for the impact of breast cancer may also prove beneficial.

Menopause and the Metabolic Syndrome: The Study of Women’s Health Across the Nation

BACKGROUND Cross-sectional studies suggest that prevalence of the metabolic syndrome (MetS) increases from premenopause to postmenopause in women, independent of age. Little is known about why. We hypothesized that the incidence of the MetS increases with progression through menopause and that this increase is explained by the progressive androgenicity of the hormonal milieu. METHODS This longitudinal, 9-year study of 949 participants in the Study of Womens Health Across the Nation investigates the natural history of the menopausal transition. Participants of 5 ethnicities at 7 geographic sites were recruited when they were premenopausal or early perimenopausal and were eligible for this study if they (1) reached menopause during the study; (2) had never taken hormone therapy, and (3) did not have diabetes mellitus or the MetS at baseline. The primary outcome was the presence of MetS using National Cholesterol Education Program Adult Treatment Panel III criteria. Secondary outcomes were the components of the MetS. RESULTS By the final menstrual period, 13.7% of the women had new-onset MetS. Longitudinal analyses, centered at the final menstrual period, were adjusted for age at menopause, ethnicity, study site, marital status, education, body mass index, smoking, and aging. Odds of developing the MetS per year in perimenopause were 1.45 (95% confidence interval, 1.35-1.56); after menopause, 1.24 (95% confidence interval, 1.18-1.30). These odds were significantly different (P < .001). An increase in bioavailable testosterone or a decrease in sex hormone-binding globulin levels increased the odds. CONCLUSIONS As testosterone progressively dominates the hormonal milieu during the menopausal transition, the prevalence of MetS increases, independent of aging and other important covariates. This may be a pathway by which cardiovascular disease increases during menopause.

Are Changes in Cardiovascular Disease Risk Factors in Midlife Women due to Chronological Aging or to the Menopausal Transition

OBJECTIVES This prospective study examined whether changes in traditional and novel coronary heart disease (CHD) risk factors are greater within a year of the final menstrual period (FMP), relative to changes that occur before or after that interval, in a multiethnic cohort. BACKGROUND Understanding the influence of menopause on CHD risk remains elusive and has been evaluated primarily in Caucasian samples. METHODS SWAN (Study of Womens Health Across the Nation) is a prospective study of the menopausal transition in 3,302 minority (African American, Hispanic, Japanese, or Chinese) and Caucasian women. After 10 annual examinations, 1,054 women had achieved an FMP not due to surgery and without hormone therapy use before FMP. Measured CHD risk factors included lipids and lipoproteins, glucose, insulin, blood pressure, fibrinogen, and C-reactive protein. We assessed which of 2 models provided a better fit with the observed risk factor changes over time in relation to the FMP: a linear model, consistent with chronological aging, or a piecewise linear model, consistent with ovarian aging. RESULTS Only total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B demonstrated substantial increases within the 1-year interval before and after the FMP, consistent with menopause-induced changes. This pattern was similar across ethnic groups. The other risk factors were consistent with a linear model, indicative of chronological aging. CONCLUSIONS Women experience a unique increase in lipids at the time of the FMP. Monitoring lipids in perimenopausal women should enhance primary prevention of CHD.

SWAN: A Multicenter, Multiethnic, Community-Based Cohort Study of Women and the Menopausal Transition

Study of Womens Health Across the Nation (SWAN) is the first national study to describe women at midlife, an understudied age group. Its multidisciplinary approach provides the opportunity to consider the contributions of both culture and biology so that one may better understand health of women. The SWAN employs a prospective design that includes sufficient pre- and postmenopausal observations to ensure the separation of menopause-related and age-related physiological changes. Other attributes include the comprehensive standardized data collection related to biological, behavioral, physiological, social, environmental, and cultural factors; specialized data collection methodologies suitable to address the monthly and yearly variation in behavioral and biological patterns; general ability to community-dwelling populations recruited from major United States population centers; sufficiently large sample size and numbers of data points to ensure reliable estimates of associations and relevant effect sizes; and inclusion of sufficient numbers of racial/ethnic minorities to provide comparative information with the non-Hispanic Caucasian population. Because of these attributes, SWAN can contribute new and substantive knowledge about womens health in general and the menopause transition in particular.

Routine follow up after head injury: a second randomised controlled trial

OBJECTIVE To confirm that patients admitted to hospital with a head injury benefit from a routinely offered early intervention service. PATIENTS AND METHODS A mixed rural and urban Health District of 560 000 people with two accident and emergency departments provided the setting. Existing routine services for most patients with head injury are minimal. All patients aged 16–65 years admitted to hospital after a head injury of any severity, with or without other injuries entered the trial. Prospective randomisation, with a block randomisation procedure was used to allocate all eligible patients to either: a group offered an additional service by a specialist team; or a group receiving existing standard services. Patients were assessed at follow up six months after injury. The primary outcome measure was the Rivermead head injury follow up questionnaire, a validated and reliable measure of social disability. The Rivermead post-concussion symptoms questionnaire was used to estimate severity of post-concussion symptoms. Each patient in the trial group was contacted 7–10 days after injury, and offered assessment and interventions as needed. These initially focused on the provision of information, support, and advice. Forty six per cent of patients in the trial group also received further outpatient intervention or additional support by telephone. RESULTS 314 patients were registered: 184 were randomised into the trial group, 130 into the control group. For prognostic data, the groups were comparable at randomisation, and remained comparable when assessed at six months. 132 trial and 86 control patients were followed up at six months after injury. Patients’ post-traumatic amnesia ranged from mild (n=79, 40%), and moderate (n=62, 32%), to severe (n=38, 19%) and very severe (n=17, 9%). The trial group patients had significantly less social disability (p=0.01) and significantly less severe post-concussion symptoms (p=0.02) at follow up at six months after injury than the control group patients. CONCLUSIONS The early interventions offered by a specialist service significantly reduced social morbidity and severity of post-concussion symptoms in trial group patients at six months after head injury. Recommendations about how specialist services should be targeted are made both in the light of these results and those from a previous randomised controlled trial.

Is there an association between menopause status and sexual functioning

Objective: The purpose of this study was to address whether: (1) there is an association between menopause status and various aspects of sexual functioning, and (2) the relative contributions of menopause status and other variables to various aspects of sexual functioning. Design: Analyses are based on 200 women from the Massachusetts Womens Health Study II, a population‐based sample of women transitioning through the menopause who were not HRT users, who had not had a surgical menopause, and who had partners. The women were classified as pre‐, peri‐, or postmenopausal according to menstrual cycle characteristics. Estradiol, estrone, and follicle‐stimulating hormone were also measured. Sexual functioning was measured in terms of satisfaction, desire, frequency of sexual intercourse, belief that interest declines with age, arousal compared with a younger age, difficulty reaching orgasm, and pain. Predictor variables included sociodemographics, health, vasomotor symptoms, psychological variables, partner variables, and lifestyle behaviors. Results: Menopause status was significantly related to lower sexual desire, a belief that interest in sexual activity declines with age, and womens reports of decreased arousal compared with when in their 40s. Menopause status was unrelated to other aspects of sexual functioning in either unadjusted or multiple regression analyses. In analyses in which log estradiol (E2) was included in addition to menopause status, log E2 was only related to pain. In multiple regression analyses, other factors such as health, marital status (or new partner), mental health, and smoking had a greater impact on womens sexual functioning than menopause status. Conclusions: Menopause status, but not E2, is related to some, but not all, aspects of sexual functioning. This may be due to menopause per se or other factors associated with menopause and aging (e.g., increased sexual dysfunction among aging men). Menopause status has a smaller impact on sexual functioning than health or other factors. (Menopause 2000;7:297‐309.

Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition

IMPORTANCE The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES To determine total duration of frequent VMS (≥ 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS The Study of Womens Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Longitudinal study of hormone levels and depression among women transitioning through menopause

Objective To address the association between depression and absolute levels of estradiol, and change in estradiol, among women during the menopausal transition. Methods This was a prospective, observational study conducted in Massachusetts, USA. Analyses reported here are based on the first three interviews following baseline (T1–T3). The participants were 309 women aged initially 43–53 years, who contributed a total of 728 observations (mean number of observations per subject 2.36). The main outcome measure was depression as measured by the Center for Epidemiologic Studies-Depression (CES-D) scale. Results CES-D score was not significantly associated with menopause status categories, nor was it associated with annual change in estradiol level (E2) (p = 0.19). The unadjusted association between log E2 and CES-D was negative (odds ratio 0.69) and statistically significant (p = 0.03). Upon adjustment for symptoms, however, the association remained negative but was no longer statistically significant (p = 0.26). Hot flushes/night sweats were positively associated with CES-D (p = 0.04), and trouble sleeping was strongly positively related to CES-D (p < 0.001). Conclusions Results provide strong support for the domino or symptom hypothesis, which posits that depressed mood is caused by vasomotor symptoms associated with changing estrogen levels. Estradiol did not have a direct effect, independent of symptoms. This study adds to the body of literature suggesting that any association found between menopause and depression is most likely to be explained by other factors, such as symptoms and sleep problems. Findings also highlight the importance of studying the complex relationship between hormone levels, sleep problems and vasomotor symptoms during the menopausal transition.

Factors Related to Age at Natural Menopause: Longitudinal Analyses From SWAN

Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Womens Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.