What do we know about the role of menopause in cardiovascular autonomic regulation in hypertensive women?

OBJECTIVE: We investigated the systemic arterial hypertension effects on cardiovascular autonomic modulation and baroreflex sensitivity (BRS) in women with or without preserved ovarian function. METHODS: A total of 120 women were allocated into two groups: middle-aged premenopausal women (42 ± 3 y old; n = 60) and postmenopausal women (57 ± 4 y old; n = 60). Each group was also divided into two smaller groups (n = 30): normotensive and hypertensive. We evaluated hemodynamic and anthropometric parameters, cardiorespiratory fitness, BRS, heart rate variability (HRV), and blood pressure variability. The effects of hypertension and menopause were assessed using a two-way analysis of variance. Post hoc comparisons were performed using the Student-Newman-Keuls test. RESULTS: Comparing premenopausal groups, women with systemic arterial hypertension showed lower BRS (9.1 ± 4.4 vs 13.4 ± 4.2 ms/mm Hg, P < 0.001 ) and HRV total variance (1,451 ± 955 vs 2,483 ± 1,959 ms 2 , P = 0.005) values than normotensive; however, the vagal predominance still remained. On the other hand, both postmenopausal groups showed an expressive reduction in BRS (8.3 ± 4.2 vs 11.3 ± 4.8 ms/mm Hg, P < 0.001) and HRV characterized by sympathetic modulation predominance (low-frequency oscillations; 56% ± 17 vs 44% ± 17, P < 0.001), in addition to a significant increase in blood pressure variability variance (28.4 ± 14.9 vs 22.4 ± 12.5 mm Hg 2 , P = 0.015) compared with premenopausal groups. Comparing both postmenopausal groups, the hypertensive group had significantly lower values ​​of HRV total variance (635 ± 449 vs 2,053 ± 1,720 ms 2 , P < 0.001) and BRS (5.3 ± 2.8 vs 11.3 ± 3.2 ms/mm Hg) than the normotensive. CONCLUSIONS: Hypertensive middle-aged premenopausal women present HRV autonomic modulation impairment, but they still maintain a vagal predominance. After menopause, even normotensive women show sympathetic autonomic predominance, which may also be associated with aging. Furthermore, postmenopausal women with hypertension present even worse cardiac autonomic modulation.

The risk of depression in the menopausal stages: A systematic review and meta-analysis.

INTRODUCTION: For many women, menopause transition can be a period of emotional and physical changes, with different menopausal stages associated with varied risk for depressive symptoms and diagnosis. This review aimed to conduct a systematic review and meta-analyses to provide an estimate for the risk of developing a) clinical depression and b) depressive symptoms at different menopausal stages. METHODS: We searched Medline, PsycInfo, Embase and Web of Science from inception to July 2023. Seventeen prospective cohort studies with a total of 16061 women were included in the review, and risk of bias was assessed using the Quality in Prognosis Studies tool (QUIPS). Seven papers with a total of 9141 participants were included in meta-analyses, using random effects models and pooled odds ratios (OR) calculated for depressive symptoms and diagnoses. RESULTS: Perimenopausal women were found to be at a significantly higher risk for depressive symptoms and diagnoses, compared to premenopausal women (OR = 1.40; 95 % CI: 1.21; 1.61, p < .001). We did not find a significantly increased risk for depressive symptoms or diagnoses in post-menopausal, compared to pre-menopausal women. LIMITATIONS: Studies used different criteria to classify the menopausal stages and different measures for depression, which may have contributed to the heterogeneity seen in some models. We were unable to include a model that compared peri to post-menopause, due to a lack of longitudinal studies comparing the two stages. CONCLUSIONS: The risk of depression in perimenopause, shown in an ethnically diverse sample; highlights the clinical need for screening and support in this potentially vulnerable group.

Association between neighborhood poverty and ovarian reserve: the ovarian aging study.

OBJECTIVE: This study aimed to examine the association between neighborhood poverty and ovarian reserve. METHODS: Among 1,019 healthy premenopausal women in the Ovarian Aging Study, aggregate exposure to neighborhood poverty was examined in relation to biomarkers of ovarian reserve, antimüllerian hormone (AMH) and antral follicle count (AFC). Specifically, the interaction of age-x-neighborhood poverty was assessed cross-sectionally to determine whether AMH and AFC declines across women may be greater in women exposed to more neighborhood poverty. Neighborhood poverty was assessed by geocoding and linking women's residential addresses in adulthood to US Census data. RESULTS: Independent of covariates, a significant interaction term showed the association between age and AMH varied by degree of exposure to neighborhood poverty in adulthood ( b = -0.001, P < 0.05). AMH declines increased progressively across women exposed to low, medium, and high levels of neighborhood poverty. In addition, main effects showed that higher neighborhood poverty was related to higher AMH in the younger women only ( b = 0.022, P < 0.01). Results related to AFC were all nonsignificant ( P > 0.05). CONCLUSIONS: Across women, greater aggregate exposure to neighborhood poverty in adulthood was related to lower ovarian reserve, indexed by AMH. In addition, there was a positive association between neighborhood poverty and AMH in younger women that attenuated in the older women. Together, results suggest that neighborhood disadvantage may have detrimental impacts that manifest as initially higher AMH, resulting in greater ovarian follicle loss over time. However, it remains unclear whether these results examining differences across women may replicate when AMH declines by neighborhood poverty are examined longitudinally.

Pelvic floor muscle strength and influencing factors based on vaginal manometry among healthy women at different life stages: A multicentre cross-sectional study.

OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.

Incidence and Outcomes Associated with Menopausal Status in COVID-19 Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Menopause causes several changes in the body that may affect the response to COVID -19. We aimed to investigate the possible association between menopausal status and incidence and outcomes in COVID-19 patients. METHODS: Combinations of keywordsCOVID-19, menopause, and estrogen were used to search the PubMed, Embase, Web-of-Science, and Scopus databases for articles reporting the incidence and outcomes of COVID-19 (discharge, length-of-admission, intensive care, or mortality) in premenopausal women, available through December 29, 2022. Data from studies comparing the incidence of COVID-19 infection with the age-matched male population were pooled and meta-analyzed using a random-effects model. RESULTS: Overall, 1,564 studies were retrieved, of which 12 were finally included in the systematic review to compare disease outcomes, and 6 were meta-analyzed for the incidence of COVID-19 in premenopausal and postmenopausal women. All studies reported better COVID-19-associated outcomes in premenopausal women compared with postmenopausal women. After adjusting for confounding factors, three studies found better outcomes in postmenopausal women, and two found no association between menopausal status and COVID-19 outcomes. Our meta-analysis found a higher incidence of COVID-19 infection among premenopausal women than postmenopausal women, when compared with age-matched men (odds ratio = 1.270; 95% confidence interval: 1.086-1.486; p = 0.003). CONCLUSION: The incidence of COVID-19 was significantly higher in premenopausal women than in postmenopausal women when compared with age-matched men. Although premenopausal women may have more favorable COVID-19-associated outcomes, the presumed preventive effect of estrogens on the incidence and related outcomes of COVID-19 in premenopausal women cannot be proven at present. Further longitudinal studies comparing pre- and post-menopausal women are required to provide further insight into this matter.

OBJETIVO: A menopausa causa diversas alterações no corpo que podem afetar a resposta ao COVID-19. Nosso objetivo foi investigar a possível associação entre o status da menopausa e a incidência e os resultados em pacientes com COVID-19. MéTODOS: Combinações de palavras-chave COVID-19, menopausa e estrogênio foram usadas para pesquisar os bancos de dados PubMed, Embase, Web-of-Science e Scopus para artigos relatando a incidência e os resultados do COVID-19 (alta, tempo de internação, tratamento intensivo cuidados ou mortalidade) em mulheres na pré-menopausa, disponível até 29 de dezembro de 2022. Dados de estudos comparando a incidência de infecção por COVID-19 com a população masculina da mesma idade foram agrupados e meta-analisados usando um modelo de efeitos aleatórios. RESULTADOS: No geral, 1.564 estudos foram recuperados, dos quais 12 foram finalmente incluídos na revisão sistemática para comparar os resultados da doença e 6 foram meta-analisados para a incidência de COVID-19 em mulheres na pré e pós-menopausa. Todos os estudos relataram melhores resultados associados ao COVID-19 em mulheres na pré-menopausa em comparação com mulheres na pós-menopausa. Após o ajuste para fatores de confusão, três estudos encontraram melhores resultados em mulheres na pós-menopausa e dois não encontraram associação entre o status da menopausa e os resultados do COVID-19. Nossa meta-análise encontrou uma maior incidência de infecção por COVID-19 entre mulheres na pré-menopausa do que mulheres na pós-menopausa, quando comparadas com homens da mesma idade (odds ratio = 1,270; intervalo de confiança de 95%: 1,086­1,486; p = 0,003). CONCLUSãO: A incidência de COVID-19 foi significativamente maior em mulheres na pré-menopausa do que em mulheres na pós-menopausa quando comparadas com homens da mesma idade. Embora as mulheres na pré-menopausa possam ter resultados mais favoráveis associados ao COVID-19, o efeito preventivo presumido dos estrogênios na incidência e nos resultados relacionados ao COVID-19 em mulheres na pré-menopausa não pode ser comprovado no momento. Mas estudos longitudinais comparando mulheres pré e pós-menopausa são necessários para fornecer mais informações sobre este assunto.

Association of ß-glucuronidase activity with menopausal status, ethnicity, adiposity, and inflammation in women.

OBJECTIVES: Many dietary polyphenols with potential health-promoting benefits undergo hepatic conjugation and circulate as inactive glucuronides that can be cleaved by ß-glucuronidase to reform the bioactive aglycone. Although indirect evidence suggests estrogen may induce ß-glucuronidase, little is known about ß-glucuronidase regulation across women's reproductive lifespan. Correlates of serum ß-glucuronidase activity in healthy premenopausal versus postmenopausal women were therefore examined. METHODS: ß-Glucuronidase activity and C-reactive protein (CRP) were assayed in stored serum from the Women's Breast and Bone Density Study, and dual-energy x-ray absorptiometry and anthropometry assessed body composition. Participants were premenopausal (n = 133) or postmenopausal (n = 89), and Hispanic (37%) or non-Hispanic White (63%). Multivariate linear regression models tested associations between ß-glucuronidase and menopausal status, ethnicity, CRP, and body composition metrics, overall and stratified by menopausal status. RESULTS: Postmenopausal (vs premenopausal) women were older (60.4 ± 3.7 vs 44.8 ± 2.4 y) with a lower Hispanic ethnicity prevalence (27% vs 44%), and higher serum ß-glucuronidase activity (1.5 ± 0.8 vs 1.3 ± 0.5 U/L) and CRP (4.2 ± 4.4 vs 3.3 ± 4.7 mg/L). Adjusting for confounders, ß-glucuronidase was positively associated with Hispanic ethnicity, CRP, body mass index, and total fat mass (all, P < 0.01), but not menopausal status nor lean mass. Central adiposity measures were also positively associated with ß-glucuronidase with the same covariates. CONCLUSIONS: ß-Glucuronidase enzyme activity, upon which polyphenol health-related benefits may depend, is not associated with menopausal status. Future studies are required to determine clinical significance and mechanisms driving ß-glucuronidase associations with ethnicity, inflammation, and adiposity in women.

Long-term changes in plasma proteomic profiles in premenopausal and postmenopausal Black and White women: the Atherosclerosis Risk in Communities study.

OBJECTIVE: The activity, localization, and turnover of proteins within cells and plasma may contribute to physiologic changes during menopause and may influence disease occurrence. We examined cross-sectional differences and long-term changes in plasma proteins between premenopausal and naturally postmenopausal women. METHODS: We used data from 4,508 (19% Black) women enrolled in the Atherosclerosis Risk in Communities study. SOMAscan multiplexed aptamer technology was used to measure 4,697 plasma proteins. Linear regression models were used to compare differences in proteins at baseline (1993-1995) and 18-year change in proteins from baseline to 2011-2013. RESULTS: At baseline, 472 women reported being premenopausal and 4,036 women reported being postmenopausal, with average ages of 52.3 and 61.4 years, respectively. A greater proportion of postmenopausal women had diabetes (15 vs 9%), used hypertension (38 vs 27%) and lipid-lowering medications (10 vs 3%), and had elevated total cholesterol and waist girth. In multivariable adjusted models, 38 proteins differed significantly between premenopausal and postmenopausal women at baseline, with 29 of the proteins also showing significantly different changes between groups over the 18-year follow-up as the premenopausal women also reached menopause. These proteins were associated with various molecular/cellular functions (cellular development, growth, proliferation and maintenance), physiological system development (skeletal and muscular system development, and cardiovascular system development and function), and diseases/disorders (hematological and metabolic diseases and developmental disorders). CONCLUSIONS: We observed significantly different changes between premenopausal and postmenopausal women in several plasma proteins that reflect many biological processes. These processes may help to understand disease development during the postmenopausal period.

Family History of Breast Cancer and Mammographic Breast Density in Premenopausal Women.

Importance: Family history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic breast density in premenopausal women is not well understood. Objectives: To investigate the association of FHBC and mammographic breast density in premenopausal women using both quantitative and qualitative measurements. Design, Setting, and Participants: This single-center cohort study examined 2 retrospective cohorts: a discovery set of 375 premenopausal women and a validation set of 14 040 premenopausal women. Data from women in the discovery set was collected between December 2015 and October 2016, whereas data from women in the validation set was collected between June 2010 and December 2015. Data analysis was performed between June 2018 and June 2020. Exposures: Family history of breast cancer (FHBC). Main Outcomes and Measures: The primary outcomes were mammographic breast density measured quantitatively as volumetric percent density using Volpara (discovery set) and qualitatively using BI-RADS (Breast Imaging Reporting and Data System) breast density (validation set). Multivariable regressions were performed using a log-transformed normal distribution for the discovery set and a logistic distribution for the validation set. Results: Of 14 415 premenopausal women included in the study, the discovery set and validation set had similar characteristics (discovery set with FHBC: mean [SD] age, 47.1 [5.6] years; 15 [17.2%] were Black or African American women and 64 [73.6%] were non-Hispanic White women; discovery set with no FHBC: mean [SD] age, 47.7 [4.5] years; 87 [31.6%] were Black or African American women and 178 [64.7%] were non-Hispanic White women; validation set with FHBC: mean [SD] age, 46.8 [7.3] years; 720 [33.4%] were Black or African American women and 1378 [64.0%] were non-Hispanic White women]; validation set with no FHBC: mean [SD] age, 47.5 [6.1] years; 4572 [38.5%] were Black or African American women and 6632 [55.8%] were non-Hispanic White women]). In the discovery set, participants who had FHBC were more likely to have a higher mean volumetric percent density compared with participants with no FHBC (11.1% vs 9.0%). In the multivariable-adjusted model, volumetric percent density was 25% higher (odds ratio [OR], 1.25 ;95% CI, 1.12-1.41) in women with FHBC compared with women without FHBC; and 24% higher (OR, 1.24; 95% CI, 1.10-1.40) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.40; 95% CI, 0.95-2.07) compared with women with no relatives affected. In the validation set, women with a positive FHBC were more likely to have dense breasts (BI-RADS 3-4) compared with women with no FHBC (BI-RADS 3: 41.1% vs 38.8%; BI-RADS 4: 10.5% vs 7.7%). In the multivariable-adjusted model, the odds of having dense breasts (BI-RADS 3-4) were 30% higher (OR, 1.30; 95% CI, 1.17-1.45) in women with FHBC compared with women without FHBC; and 29% higher (OR, 1.29; 95% CI, 1.14-1.45) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.38; 95% CI, 0.85-2.23) compared with women with no relatives affected. Conclusions and Relevance: In this cohort study, having an FHBC was positively associated with mammographic breast density in premenopausal women. Our findings highlight the heritable component of mammographic breast density and underscore the need to begin annual screening early in premenopausal women with a family history of breast cancer.

The Importance of Being a 'Lark' in Post-Menopausal Women with Obesity: A Ploy to Prevent Type 2 Diabetes Mellitus?

Chronotype is defined as the behavioral manifestation of circadian rhythms related to the external light-dark cycle. Evening chronotype has been associated with an increased risk of developing cardiometabolic diseases in obesity. Menopause is a lifestage associated with an increased risk of developing cardiometabolic diseases and a change in circadian rhythmicity compared to pre-menopause. However, the prevalence of chronotype categories in menopause and their role in determining menopause-related cardiometabolic risk, mostly in obesity, have not been investigated. Thus, we aimed to investigate the prevalence of chronotype categories in post-menopausal women with obesity and their role in menopause-related cardiometabolic risk. In this cross-sectional study we enrolled 49 pre-menopausal and 74 post-menopausal women with obesity. Anthropometric parameters, lifestyle habits, adherence to the Mediterranean Diet (MD), sleep quality, chronotype and the presence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) were studied. No significance differences were detected in terms of lifestyle and adherence to the MD between pre- and post-menopausal women. Chronotype was classified as morning in 66 (53.6%), evening in 20 (16.3%) and intermediate in 37 (30.1%) women. In addition, pre-menopausal women with obesity showed a significantly higher chance to have an intermediate chronotype (OR = 2.21, 95% CI 1.28-3.83; p = 0.004), whereas post-menopausal women with obesity showed a trend to have a higher morning chronotype (OR = 1.42, 95% CI 0.98-2.06; p = 0.051), although this did not reach statistical significance. No significant differences were detected in terms of prevalence of evening chronotype between the two groups. However, the evening chronotype had a significantly higher risk to have T2DM compared to the morning (OR = 17.29, 95% CI 2.40-124.27; p = 0.005) and intermediate chronotypes (OR = 30.86, 95% CI 2.05-464.32; p = 0.013) in both pre- and post-menopausal women with obesity. In conclusion, the intermediate chronotype was significantly more prevalent in pre-menopausal women with obesity compared to post-menopausal women. Evening chronotype was associated to T2DM in both pre- and post-menopause. These results support the importance of including the assessment of chronotype in the management of women with obesity in post-menopause.

Myocardial Function in Premenopausal Women Treated With Ovarian Function Suppression and an Aromatase Inhibitor.

Background: Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) with aromatase inhibitor therapy; however, abrupt menopause induction, together with further decrements in estrogen exposure through aromatase inhibition, may affect cardiovascular microcirculatory function. We examined adenosine-induced changes in left ventricular (LV) myocardial T1, a potential subclinical marker of LV microcirculatory function in premenopausal women undergoing treatment for breast cancer. Methods: Twenty-one premenopausal women (14 with HR-positive breast cancer receiving OFS with an aromatase inhibitor and 7 comparator women with triple-negative breast cancer [TNBC] who had completed primary systemic therapy) underwent serial resting and adenosine cardiovascular magnetic resonance imaging measurements of LV myocardial T1 and LV volumes, mass, and ejection fraction. All statistical tests were 2-sided. Results: After a median of 4.0 months (range = 3.1-5.7 months), the stress to resting ratio of LV myocardial T1 declined in women with HR-positive breast cancer (-1.3%, 95% confidence interval [CI] = -3.4% to 0.7%) relative to those with TNBC (3.2%, 95% CI = -1.2% to 7.6%, P = .02). After accounting for age, LV stroke volume, LV ejection fraction, diastolic blood pressure, and breast cancer subtype women with HR-positive breast cancer experienced a blunted T1 response after adenosine relative to women with TNBC (difference = -4.7%, 95% CI = -7.3% to -2.1%, P difference = .002). Conclusions: Over the brief interval examined, women with HR-positive breast cancer receiving OFS with an aromatase inhibitor experienced reductions in adenosine-associated changes in LV myocardial T1 relative to women who received nonhormonal therapy for TNBC. These findings suggest a possible adverse impact on LV myocardial microcirculatory function in premenopausal women with breast cancer receiving hormone deprivation therapy.

Association between body composite indices and vertebral fractures in pre and postmenopausal women in Korea.

The association between obesity and vertebral fracture remains controversial. This study aimed to investigate the association between obesity/abdominal obesity and vertebral fracture according to menopausal status. This nationwide population-based epidemiologic study collected data from the Korean National Health Insurance Services to investigate the association between obesity/abdominal obesity and vertebral fracture in pre and postmenopausal women who underwent national cancer screening in 2009. We used three body composite indices of obesity, body mass index, waist circumference and waist-to-height ratio, to classify participants into obesity and abdominal obesity groups. In both pre and postmenopausal groups, participants with obesity showed a higher risk of vertebral fracture and the association was stronger in those with abdominal obesity (p < 0.001). Participants with obesity showed a high risk of vertebral fracture, and the association was stronger in participants with abdominal obesity (p < 0.001). In both pre and postmenopausal groups, participants with obesity showed a higher risk of vertebral fracture (adjusted HR, 1.24; 95% CI, 1.19-1.30), (adjusted HR, 1.04; 95% CI, 1.03-1.05, and those with abdominal obesity showed even higher risk of vertebral fractures (adjusted HR, 1.35; 95% CI, 1.27-1.43), (adjusted HR, 1.13; 95% CI, 1.11-1.14). Vertebral fracture risk is higher in pre and postmenopausal women with obesity and even higher in those with abdominal obesity. Therefore, weight management can prevent vertebral fractures.

Association between skeletal muscle mass and mammographic breast density.

Mammographic density (MD) of the breast and body mass index (BMI) are inversely associated with each other, but have inconsistent associations with respect to the risk of breast cancer. Skeletal muscle mass index (SMI) has been considered to reflect a relatively accurate fat and muscle percentage in the body. So, we evaluated the relation between SMI and MD. A cross-sectional study was performed in 143,456 women who underwent comprehensive examinations from 2012 to 2016. BMI was adjusted to analyze whether SMI is an independent factor predicting dense breast. After adjustment for confounding factors including BMI, the odds ratios for MD for the dense breasts was between the highest and lowest quartiles of SMI at 2.65 for premenopausal women and at 2.39 for postmenopausal women. SMI was a significant predictor for MD, which could be due to the similar growth mechanism of the skeletal muscle and breast parenchymal tissue. Further studies are needed to understand the causal link between muscularity, MD and breast cancer risk.

Adolescent and early adulthood inflammation-associated dietary patterns in relation to premenopausal mammographic density.

BACKGROUND: Adolescence and early adulthood has been identified as a critical time window for establishing breast cancer risk. Mammographic density is an independent risk factor for breast cancer that may be influenced by diet, but there has been limited research conducted on the impact of diet on mammographic density. Thus, we sought to examine the association between adolescent and early adulthood inflammatory dietary patterns, which have previously been associated with breast cancer risk, and premenopausal mammographic density among women in the Nurses' Health Study II (NHSII). METHODS: This study included control participants with premenopausal mammograms from an existing breast cancer case-control study nested within the NHSII who completed a Food Frequency Questionnaire in 1998 about their diet during high school (HS-FFQ) (n = 685) and/or a Food Frequency Questionnaire in 1991 (Adult-FFQ) when they were 27-44 years old (n = 1068). Digitized analog film mammograms were used to calculate the percent density, absolute dense, and non-dense areas. Generalized linear models were fit to evaluate the associations of a pro-inflammatory dietary pattern and the Alternative Healthy Eating Index (AHEI, an anti-inflammatory dietary pattern) with each breast density measure. RESULTS: Significant associations were observed between an adolescent pro-inflammatory dietary pattern and mammographic density in some age-adjusted models; however, these associations did not remain after adjustment for BMI and other breast cancer risk factors. No associations were observed with the pro-inflammatory pattern or with the AHEI pattern in adolescence or early adulthood in fully adjusted models. CONCLUSIONS: To our knowledge, this is the first study to evaluate the dietary patterns during adolescence and early adulthood in relation to mammographic density phenotypes. Our findings do not support an association between adolescent and early adulthood diet and breast density in mid-adulthood that is independent of BMI or other breast cancer risk factors.

Vitamin D status determines the impact of metformin on circulating prolactin levels in premenopausal women.

WHAT IS KNOWN AND OBJECTIVE: Metformin was found to normalize secretory function of overactive pituitary cells. Its effect on circulating thyrotropin levels was more pronounced in women receiving exogenous vitamin D. The aim of the current study was to investigate whether vitamin D status determines the impact of metformin on prolactin levels in premenopausal women with hyperprolactinaemia. METHODS: The study population consisted of three groups of women with prediabetes and elevated prolactin levels: vitamin D-naïve women with vitamin D insufficiency (group 1; n = 19), women receiving vitamin D preparations because of vitamin D deficiency (group 2 n = 20), as well as vitamin D-naïve women with normal vitamin D status (group 3 n = 23). All participants were then treated with metformin (2.55-3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin were determined at baseline and six months later. RESULTS AND DISCUSSION: At baseline, prolactin levels were higher in group 1 than in the remaining groups of patients. Although metformin decreased glucose levels and improved insulin sensitivity in all treatment groups, this effect was more pronounced in groups 2 and 3. Only in subjects with 25-hydroxyvitamin D levels within the reference range, metformin reduced prolactin levels. The impact on prolactin levels correlated with 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. The drug produced a neutral effect on circulating levels of thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin D. WHAT IS NEW AND THE CONCLUSION: The results of the current study suggest that the impact of metformin on secretory function of overactive lactotropes depends on the vitamin D status of patients.

What happens after menopause? (WHAM): A prospective controlled study of sleep quality up to 12 months after premenopausal risk-reducing salpingo-oophorectomy.

OBJECTIVE: Sleep difficulties impair function and increase the risk of depression at menopause and premenopausal oophorectomy may further worsen sleep. However, prospective data are limited, and it remains uncertain whether Hormone Therapy (HT) improves sleep. This prospective observational study measured sleep quality before and up to 12 months after risk-reducing salpingo-oophorectomy (RRSO) compared to a similar age comparison group who retained their ovaries. METHODS: Ninety-five premenopausal women undergoing RRSO and 99 comparisons were evaluated over a 12-month period using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Almost half reported poor sleep quality at baseline. Overall sleep quality was not affected by RRSO until 12 months (p = 0.007). However, sleep disturbance increased by 3 months and remained significantly elevated at 12 months (p < 0.001). Trajectory analysis demonstrated that 41% had increased sleep disturbance after RRSO which persisted in 17.9%. Risk factors for sleep disturbance included severe vasomotor symptoms, obesity and smoking. Around 60% initiated HT after RRSO. Sleep quality was significantly better in HT users vs non users (p = 0.020) but HT did not restore sleep quality to baseline levels. CONCLUSIONS: Overall sleep quality is not affected by RRSO, but new onset sleep disturbance is common, particularly in those with severe vasomotor symptoms. Clinicians should be alert to new-onset sleep disturbance and the potential for HT to improve sleep quality.

High Circulating Follicle-Stimulating Hormone Level Is a Potential Risk Factor for Renal Dysfunction in Post-Menopausal Women.

Objective: Menopause contributes to renal dysfunction in women, which is generally attributed to estrogen withdrawal. In addition to decreased estrogen level, serum follicle-stimulating hormone (FSH) level increases after menopause. This study investigated the association between high circulating FSH level and renal function in post-menopausal women. Methods: This observational cross-sectional study included 624 pre-menopausal, 121 peri-menopausal, and 2540 post-menopausal women. The levels of female sex hormones were examined by chemiluminescence and indices of renal function were measured using a clinical chemistry analyzer. The post-menopausal women were grouped into quartiles according to serum FSH levels. Results: Renal function progressively declined from pre-menopause to peri-menopause to post-menopause, which was accompanied by increasing serum FSH level. In post-menopausal women, serum creatinine level increased with increasing FSH quartile, which was accompanied by a decrease in estimated glomerular filtration rate (eGFR) (p for trend <0.001); moreover, the prevalence of declined eGFR (<90 ml/min/1.73 m2) and chronic kidney disease (CKD; eGFR <60 ml/min/1.73 m2) increased (p for trend <0.001). Even after adjusting for confounders, the odds ratios (ORs) of declined eGFR and CKD increased with increasing FSH quartiles in post-menopausal women. The ORs of declined eGFR (OR=2.19, 95% confidence interval [CI]: 1.63-2.92) and CKD (OR=10.09, 95% CI: 2.28-44.65) in the highest FSH quartile were approximately 2- and 10-fold higher, respectively, than in the lowest FSH quartile (p<0.05). After stratifying post-menopausal women by median age (61 years), the OR for declined eGFR for each FSH quartile in the older group was higher than that for the corresponding FSH quartile in the younger group. Conclusions: A high circulating FSH level is an independent risk factor for renal dysfunction in women after menopause. Additionally, aging may aggravate the association of high FSH levels with reduced renal function in post-menopausal women.

Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women.

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real-world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN-BMD) were well-described by a bi-exponential relationship with first-order BMD formation (k1 ) and resorption (k2 ) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25-maximum 53]) lose 0.6% FN-BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10-year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN-BMD of 0.975 g/cm2 at menopause, associated with a 10-year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long-term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.

Vitamin D as a risk factor for the presence of asymptomatic uterine fibroids in premenopausal Han Chinese women.

OBJECTIVES: To investigate the relationship between vitamin D deficiency and the risk of asymptomatic uterine fibroids (UFs). DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): The present analysis recruited 133 asymptomatic patients with UFs and 80 normal control subjects from October 2017 to June 2020. Age matching created 61 pairs. INTERVENTION(S): Medical history, transvaginal or transabdominal genital ultrasound scan, blood sampling, and measurement of vitamin D concentrations. MAIN OUTCOME MEASURE(S): Evaluation of the impact of vitamin D level on the risk of newly diagnosed asymptomatic UFs in premenopausal Han Chinese women. RESULT(S): Vitamin D levels of UF-positive patients were lower than those of healthy control subjects in unmatched samples (12.1 ng/mL vs. 16.8 ng/mL) and in matched samples (11.4 vs. 17.5 ng/mL). Younger patients (≤40 years) had a lower vitamin D level than older subjects in healthy control group (15.1 ng/mL vs. 19.0 ng/mL). We did not observe any age-vitamin D interactive effect in unmatched samples. Multivariate logistic regression revealed that asymptomatic patients presented a lower level of vitamin D than did normal groups in both unmatched and matched sample. In addition, the optimal threshold vitamin D level for having asymptomatic UFs was 14.34 ng/mL. CONCLUSION(S): Vitamin D deficiency may be associated with increased risk of asymptomatic UFs in premenopausal Han Chinese women.

Are the factors associated with overweight/general obesity and abdominal obesity different depending on menopausal status?

Rapid modernization in China has impacted the daily lives and health of women, including a rise in obesity. However, little is known about the impact of menopausal status, behavior, and psychosocial factors on the risk of obesity for rural women in China. The aim of this study is to identify risk factors, including demographic information (education, family history of T2DM, menopausal status), obesity-related behavior, and psychosocial factors associated with overweight/general obesity and abdominal obesity. In a cross-sectional study design, participants had their weight, height, and waist circumference measured and completed questionnaires regarding family demographics, obesity-related health behaviors (physical activity, diet, sleep), and psychosocial information (stress, social support, and self-efficacy related to physical activity and healthy diet). A total of 646 women were included in this study; 46.6% were overweight/generally obese, and 48% had abdominal obesity. Postmenopausal women had a higher prevalence of general and central obesity. Regular physical activity decreased the risk for overweight/general obesity and abdominal obesity (OR = .41 and .31, respectively, p = .04) in premenopausal women. Postmenopausal women who had not breastfed their infants and reported moderate/high-stress had a higher risk for overweight/general obesity (OR = 3.93, and 2, respectively) and those who reported less than 6 hours of sleep per day increased their risk for abdominal obesity (OR = 2.08). Different factors associated with obesity were found in Chinese women, depending on menopausal status. Future studies should examine the impact of menopause on a woman's risk for obesity, as well as develop tailored interventions to improve health, well-being and reduce the risk of obesity.