Vasomotor symptoms and cardiovascular health: findings from the SWAN and the MsHeart/MsBrain studies.

Vasomotor symptoms (VMS) are often considered the classic menopausal symptom and are experienced by most women during the menopause transition. VMS are well established to be associated with decrements in quality of life during the menopause. More recent research also links VMS to poorer cardiovascular health. This review summarizes key insights about links between VMS and cardiovascular disease (CVD) risk that come from the Study of Women's Health Across the Nation (SWAN), a longitudinal epidemiologic cohort study of the menopause transition, as well as from the MsHeart/MsBrain studies, clinical studies that leverage vascular imaging and brain imaging as well as wearable technologies that provide objective indicators of VMS. Using a range of methodologies and extensive consideration of confounders, these studies have shown that frequent and/or persistent VMS are associated with adverse CVD risk factor profiles, poorer underlying peripheral vascular and cerebrovascular health, and elevated risk for clinical CVD events. Collectively, the SWAN and MsHeart/MsBrain studies form complementary epidemiologic and clinical studies that point to the importance of VMS to women's cardiovascular health during the menopause transition and beyond.

Uncovering the "riddle of femininity" in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment.

OBJECTIVE: Post-menopausal women are disproportionately affected by osteoarthritis (OA). As such, the purpose of this study was to (1) summarize the state-of-the-science aimed at understanding the effects of menopause on OA in animal models and (2) investigate how dosage and timing of initiation of estrogen treatment affect cartilage degeneration. DESIGN: A systematic review identified articles studying menopausal effects on cartilage in preclinical models. A meta-analysis was performed using overlapping cartilage outcomes in conjunction with a rigor and reproducibility analysis. Ordinary differential equation models were used to determine if a relationship exists between cartilage degeneration and the timing of initiation or dosage of estrogen treatment. RESULTS: Thirty-eight manuscripts were eligible for inclusion. The most common menopause model used was ovariectomy (92%), and most animals were young at the time of menopause induction (86%). Most studies did not report inclusion criteria, animal monitoring, protocol registration, or data accessibility. Cartilage outcomes were worse in post-menopausal animals compared to age-matched, non-menopausal animals, as evidenced by cartilage histological scoring [0.75, 1.72], cartilage thickness [-4.96, -0.96], type II collagen [-4.87, -0.56], and c-terminal cross-linked telopeptide of type II collagen (CTX-II) [2.43, 5.79] (95% CI of Effect Size (+greater in menopause, -greater in non-menopause)). Moreover, modeling suggests that cartilage health may be improved with early initiation and higher doses of estrogen treatment. CONCLUSIONS: To improve translatability, animal models that consider aging and natural menopause should be utilized, and more attention to rigor and reproducibility is needed. Timing of initiation and dosage may be important factors modulating therapeutic effects of estrogen on cartilage.

Racial/Ethnic Differences in Women's Life Event Exposure Across Midlife.

OBJECTIVE: Stressful life events are associated with poorer physical, cognitive, and mental health. Examining life events trends across midlife illustrates normative experiences of stress in a critical life period for intervention and disease prevention. Further, there is a critical need for research with racially/ethnically diverse samples to identify differences in life event exposure, as they may relate to later health disparities. METHOD: Annual life event reports were analyzed from 3,066 White, Black, Hispanic, Chinese, and Japanese women in the Study of Women's Health Across the Nation. Across ages 43-65, longitudinal trajectories were fit to annual number of life events and 9 subcategories of life events (i.e., work problems, economic problems, partner unemployment, illness/accident of loved one, caregiving, bereavement, relationship problems, family legal/police problems, and violent events that happened to the self or family). Racial/ethnic differences were examined, controlling for education. RESULTS: Number of annual life events declined with age and plateaued in later midlife. This pattern was largely consistent across types of life events, though family health and bereavement-related life events increased in later midlife. Compared to White women, Black women experienced more life events, while Chinese, Hispanic, and Japanese women experienced fewer life events. Racial/ethnic differences were amplified in specific subtypes of life events. DISCUSSION: Racial/ethnic differences in exposure to life events across midlife may contribute to racial/ethnic health disparities in later life.

Vasomotor symptoms: natural history, physiology, and links with cardiovascular health.

Vasomotor symptoms (VMS), or hot flushes and night sweats, are the classic symptom of menopause. Recent years have brought key advances in the knowledge about VMS. VMS last longer than previously thought, on average 7-10 years for frequent or moderate to severe VMS. Although VMS have long been understood to be important to women's quality of life, research has also linked VMS to indicators of cardiovascular disease (CVD) risk, such as an adverse CVD risk factor profile, greater subclinical CVD and, in emerging work, CVD events. Relations between VMS and CVD are not typically accounted for by CVD risk factors. In newer work, VMS-CVD risk relations are demonstrated with state-of-the-art subjective and objective measures of VMS. Some research indicates that VMS-CVD risk relations may be sensitive to the timing or duration of VMS. Thus, research collectively supports relations between VMS and CVD risk independent of known CVD risk factors. Next steps include identifying the mechanisms linking VMS and CVD risk indicators, understanding any timing effects, and clarifying the precise nature of relations between VMS and CVD risk. Clinical implications are discussed.

Association between changes in oestradiol and follicle-stimulating hormone levels during the menopausal transition and risk of diabetes.

AIM: To investigate the association between changes in oestradiol and follicle-stimulating hormone levels during the menopausal transition and incident diabetes. METHODS: We followed 1407 pre-menopausal women, aged 42-52 years at baseline, who experienced natural menopause, from baseline to the 12th annual follow-up visit in the Study of Women's Health Across the Nation (SWAN). Diabetes was defined based on fasting glucose level, medication use and self-report of physician diagnosis. Cox proportional hazards regression was used to evaluate the associations of incident diabetes with three components of the rate of change in hormones: the intercept (pre-menopausal levels) and two piece-wise slopes representing change during the early and late transition, respectively. RESULTS: During 15 years of follow-up, 132 women developed diabetes. After adjusting for potential confounders, a higher oestradiol intercept, but not its rate of change, was borderline significantly associated with lower risk of diabetes [hazard ratio for an interquartile range increase (75.2 pmol/L) 0.53, 95% CI 0.27-1.06]. For follicle-stimulating hormone, a greater rate of increase in the early transition, but not the intercept or late transition, was significantly associated with lower risk of diabetes [hazard ratio for an interquartile range increase (5.9 IU/L/year) 0.31, 95% CI 0.10-0.94]. CONCLUSIONS: Lower pre-menopausal oestradiol levels and a slower rate of follicle-stimulating hormone change during the early transition were associated with higher risk of developing diabetes. Given that obesity plays an important role in diabetes risk and in the levels and changes in oestradiol and follicle-stimulating hormone over the menopausal transition, weight control in earlier mid-life is important to prevent future diabetes development.

Assessment of hot flushes and vaginal dryness among obese women undergoing bariatric surgery.

OBJECTIVE: Menopausal symptoms are associated with a negative impact on the quality of life, leading women to seek medical treatment. Obesity has been linked to higher levels of menopausal symptoms such as hot flushes. This assessment will explore whether the prevalence and bother of hot flushes and vaginal dryness change from pre- to post-bariatric surgery among obese midlife women. METHODS: This study is a longitudinal analysis of data from 69 women (ages 35-72 years) undergoing bariatric surgery with reported reproductive histories and menopausal symptoms at preoperative and 6-month postoperative visits. Prevalence of and degree of bother of hot flushes and vaginal dryness at pre- and post-surgery were compared using McNemar's test and Wilcoxon signed-rank test. RESULTS: The reported degree of bother of symptoms associated with hot flushes decreased from pre- to post-surgery (p < 0.01). There was no significant change in the prevalence of hot flushes or vaginal dryness in the overall study sample. CONCLUSIONS: The degree of bother of symptoms associated with hot flushes among midlife women may decrease after bariatric surgery. These results highlight important secondary gains, including less bothersome menopausal symptoms, for women who choose bariatric surgery for weight loss.

Associations between adjuvant endocrine therapy and onset of physical and emotional concerns among breast cancer survivors.

BACKGROUND: Breast cancer survivors often receive long-term adjuvant endocrine therapy (AET) to reduce recurrence risk. Adherence to AET is suboptimal, which may be due to the experience of symptoms and/or concerns. Few studies have comprehensively assessed self-reported concerns between those who currently, previously or have never received AET. The study objective is to describe self-reported physical and emotional concerns of breast cancer survivors who are current, prior, or never-recipients of AET. METHODS: Secondary analysis was performed on a subset of survey data collected in the 2010 LIVESTRONG Survey. Breast cancer survivors (n = 1,013, mean 5.4 years post-diagnosis) reported on 14 physical and eight emotional concerns that began after diagnosis and were experienced within 6 months of participation in the survey. Bivariate analyses examined the prevalence of each concern by AET status. The relationships between AET and burden of physical or emotional concerns were modeled with logistic regression. RESULTS: More than 50% of the participants reported currently experiencing cognitive issues, fatigue, fear of recurrence, emotional distress, and identity/grief issues. Thyroid dysfunction and stigma concerns were more common among participants with prior AET (p < 0.01), while fear of recurrence, emotional distress, and concern about appearance were more common among those currently receiving AET (p < 0.01). Fatigue, sexual dysfunction, and pain were more common among prior and current AET recipients (p < 0.01). In adjusted models, receipt of AET was associated with a higher number of physical, but not emotional concerns. A higher number of concerns was associated with younger age, having children, receipt of chemotherapy, longer duration of cancer treatment, and shorter time since diagnosis (p < 0.01). CONCLUSIONS: Breast cancer survivors who received AET were at risk of developing a variety of physical and emotional concerns, many of which persisted after treatment. These findings suggest the importance of developing individualized, supportive resources for breast cancer survivors.

Body mass index following natural menopause and hysterectomy with and without bilateral oophorectomy.

OBJECTIVE: The directional and temporal nature of relationships between overweight and obesity and hysterectomy with or without oophorectomy is not well understood. Overweight and obesity may be both a risk factor for the indications for these surgeries and a possible consequence of the procedure. We used prospective data to examine whether body mass index (BMI) increased more following hysterectomy with and without bilateral oophorectomy compared with natural menopause among middle-aged women. METHODS: BMI was assessed annually for up to 10 years in the Study of Women's Health Across the Nation (SWAN (n=1962)). Piecewise linear mixed growth models were used to examine changes in BMI before and after natural menopause, hysterectomy with ovarian conservation and hysterectomy with bilateral oophorectomy. Covariates included education, race/ethnicity, menopausal status, physical activity, self-rated health, hormone therapy use, antidepressant use, age and visit before the final menstrual period (FMP; for natural menopause) or surgery (for hysterectomy/oophorectomy). RESULTS: By visit 10, 1780 (90.6%) women reached natural menopause, 106 (5.5%) reported hysterectomy with bilateral oophorectomy and 76 (3.9%) reported hysterectomy with ovarian conservation. In fully adjusted models, BMI increased for all women from baseline to FMP or surgery (annual rate of change=0.19 kg m(-2) per year), with no significant differences in BMI change between groups. BMI also increased for all women following FMP, but increased more rapidly in women following hysterectomy with bilateral oophorectomy (annual rate of change=0.21 kg m(-2) per year) as compared with following natural menopause (annual rate of change=0.08 kg m(-2) per year, P=0.03). CONCLUSION: In this prospective examination, hysterectomy with bilateral oophorectomy was associated with greater increases in BMI in the years following surgery than following hysterectomy with ovarian conservation or natural menopause. This suggests that accelerated weight gain follows bilateral oophorectomy among women in midlife, which may increase risk for obesity-related chronic diseases.