Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study.

BACKGROUND: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. METHODS: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. RESULTS: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. CONCLUSIONS: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.

Correlation between serum vitamin D levels and bone mass density evaluated by radiofrequency echographic multi-spectrometry technology (REMS) in menopausal women.

Osteoporosis is a common condition associated with an increased risk of bone fractures due to fragility. Bone mineral density (BMD) is lower in menopausal women due to estrogen deficiency, age-related decline in osteoblast function, decreased calcium absorption, and reduced synthesis of vitamin D, which lead to osteoporosis. The aim of this study was to determine the correlation between serum vitamin D levels and BMD assessed using radiofrequency echographic multi-spectrometry technology (REMS) in menopausal women. A cross-sectional study was conducted at Prof. Dr. Chairuddin P. Lubis Hospital of Universitas Sumatera Utara, Medan, Indonesia, from May 2023 to August 2023. Consecutive sampling method was employed to sample menopausal women with no history of hysterectomy or oophorectomy (unilateral or bilateral), and no history of hormone replacement therapy or vitamin D supplementation. Interviews and physical examinations were conducted to obtain the characteristics of the subjects (age, duration of menopause, and body mass index). The 25(OH)D level was measured using immunoassay and REMS examination was conducted to assess BMD. The Spearman correlation test was used to assess the correlation between serum vitamin D levels and BMD. A total of 32 menopausal women were included in this study with the average vitamin D level was 18.05±5.81 ng/mL, and the mean BMD level was -2.13±1.23. The data showed a significant positive correlation between serum vitamin D levels and BMD in menopausal women (r=0.710; p=0.020). This study highlights that REMS could be useful as an alternative to dual-energy x-ray absorptiometry (DXA) to assess DMD in postmenopausal women.

A murine model of hypertensive heart disease in older women.

We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life. We observed that AngII effects on heart morphology were different in younger and adult mice (3- and 12-month-old; 20 and 19% increase in heart weight. P < 0.01 for both) than in older animals (24-month-old; 6%; not significant). Ovariectomy at 12 months restored the hypertrophic response to AngII in elderly females (23%, p = 0.0001). We performed a bulk RNA sequencing study of the left ventricle (LV) and left atrial gene expression in elderly animals, controls, and Ovx. AngII modulated (|Log2 fold change| ≥ 1) the LV expression of 170 genes in control females and 179 in Ovx ones, 64 being shared. In the left atrium, AngII modulated 235 genes in control females and 453 in Ovx, 140 shared. We observed many upregulated genes associated with the extracellular matrix regulation in both heart chambers. Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed Ankrd1, Nppb, Col3a1, Col1a1, Ctgf Col8a1, and Cilp. Several circadian clock LV genes were modulated differently by AngII between control and Ovx females (Clock, Arntl, Per2, Cry2, and Ciart). In conclusion, sex hormones, even in elderly female mice, modulate the heart's hypertrophic response to AngII. Our study identifies potential new markers of hypertensive disease in aging female mice and possible disturbances of their cardiac circadian clock.

Sexual Dysfunction After Menopause: Guidelines for Assessment and Management.

Female sexual dysfunction commonly occurs during the menopause transition and post-menopause due to hormonal, physiologic, and psychosocial factors. Sexuality is important to aging women; however, many are reluctant to seek treatment for their sexual concerns. Clinicians should be adept at managing and treating sexual dysfunction in this population. A multi-dimensional treatment approach that addresses modifiable mental, physical, and psychosocial factors is warranted to improve sexual function and quality of life.

Association of menopausal status with body composition and anthropometric indices in Korean women.

BACKGROUND: Menopause induces various health problems and is associated with obesity, but the association between menopausal status and obesity is unclear due to several confounding factors, such as aging and reduced physical activity. The objective of this study was to examine the association of menopausal status with anthropometric indices and body composition indices in South Korean women. METHODS: In this cross-sectional study, a total of 734 subjects (297 postmenopausal women, 437 premenopausal women) from five university hospitals in South Korea were included. A binary logistic regression analysis was performed to examine the association of menopause with anthropometric indices and body composition indices. RESULTS: Height, body mass index, waist-to-height ratio, waist-to-hip ratio, and neck, armpit, chest, rib, waist, iliac, and hip circumferences were associated with menopausal status in the crude analysis, but these associations disappeared in the adjusted models. Among the body composition indices, menopausal status was strongly associated with total body water, skeletal muscle mass, body fat mass, and body fat percentage in the crude analysis. However, the associations with body fat mass and body fat percentage disappeared in the adjusted models. Only the associations with total body water and skeletal muscle mass remained in the adjusted models. CONCLUSION: Most of the anthropometric indices and body composition indices were not associated with menopausal status, but total body water and skeletal muscle mass were significantly lower in postmenopausal women than in premenopausal women.

Vitamin D and Menopause.

Menopause is the transition period in female life cycle. Resultant hormonal changes lead to adverse health effects. Women may seek treatment due to significant impairment in quality of life. Vitamin D deficiency is a globally prevalent problem. Vitamin D deficiency in menopausal women may aggravate the adverse health risks associated with menopause. In this article, the authors discuss endocrinology and clinical features of menopause, Vitamin D and its links with menopause, and the potential role of Vitamin D supplementation to combat detrimental multi-organ system effects of menopause.

The Effect of Yoga on Menopause Symptoms: A Randomized Controlled Trial.

The research was conducted as a randomized controlled study with the aim of determining the effect of yoga on menopause symptoms. Menopausal women between the ages of 40 and 60 years were included in the research. There were 31 menopausal women in each of 2 groups, making a total of 62. A Descriptive Characteristics Form and the Menopause Rating Scale (MRS) were used to collect data. In the research, the yoga group practiced yoga for 60 minutes twice a week for 10 weeks. In the final lesson of the 10 weeks of yoga training, the women were again given the MRS. No intervention was performed on the control group. The median score on the MRS of the women in the yoga group was 16 (11-21) in the pretest, and 5 (3-9) in the posttest (P < .05). The median score on the subscale of psychological complaints of the women in the yoga group was 6 (3-8) in the pretest, and 1 (1-2) in the posttest (P < .05). The median score on the subscale of urogenital complaints of the women in the yoga group was 3 (3-5) in the pretest, and 1 (0-2) in the posttest (P < .05). The median score on the subscale of somatic complaints of the women in the yoga group was 7 (4-10) in the pretest, and 1 (1-3) in the posttest (P < .05). It was concluded from the research that 60 minutes of yoga 2 days a week for 10 weeks may reduce the psychological, somatic, and urogenital symptoms experienced in menopause.

A causal examination of the correlation between hormonal and reproductive factors and low back pain.

Background: The relationship between hormonal fluctuations in the reproductive system and the occurrence of low back pain (LBP) has been widely observed. However, the causal impact of specific variables that may be indicative of hormonal and reproductive factors, such as age at menopause (ANM), age at menarche (AAM), length of menstrual cycle (LMC), age at first birth (AFB), age at last live birth (ALB) and age first had sexual intercourse (AFS) on low back pain remains unclear. Methods: This study employed Bidirectional Mendelian randomization (MR) using publicly available summary statistics from Genome Wide Association Studies (GWAS) and FinnGen Consortium to investigate the causal links between hormonal and reproductive factors on LBP. Various MR methodologies, including inverse-variance weighted (IVW), MR-Egger regression, and weighted median, were utilized. Sensitivity analysis was conducted to ensure the robustness and validity of the findings. Subsequently, Multivariate Mendelian randomization (MVMR) was employed to assess the direct causal impact of reproductive and hormone factors on the risk of LBP. Results: After implementing the Bonferroni correction and conducting rigorous quality control, the results from MR indicated a noteworthy association between a decreased risk of LBP and AAM (OR=0.784, 95% CI: 0.689-0.891; p=3.53E-04), AFB (OR=0.558, 95% CI: 0.436-0.715; p=8.97E-06), ALB (OR=0.396, 95% CI: 0.226-0.692; p=0.002), and AFS (OR=0.602, 95% CI: 0.518-0.700; p=3.47E-10). Moreover, in the reverse MR analysis, we observed no significant causal effects of LBP on ANM, AAM, LMC and AFS. MVMR analysis demonstrated the continued significance of the causal effect of AFB on LBP after adjusting for BMI. Conclusion: Our study explored the causal relationship between ANM, AAM, LMC, AFB, AFS, ALB and the prevalence of LBP. We found that early menarche, early age at first birth, early age at last live birth and early age first had sexual intercourse may decrease the risk of LBP. These insights enhance our understanding of LBP risk factors, offering valuable guidance for screening, prevention, and treatment strategies for at-risk women.

Menopausal Hormone Therapy, an Ever-Present Topic: A Pilot Survey about Women's Experience and Medical Doctors' Approach.

Background and Objective: Menopause can be associated with many clinical manifestations: vasomotor symptoms, urogenital problems, and additional psychological disturbances, such as anxiety, mood changes, and sleep alterations. The prolonged lack of hormones also increases the risk of long-term consequences. Hormone Replacement Treatment (HRT) in menopause consists of the administration of estrogen, alone or associated to progesterone, to relieve these uncomfortable disturbances and to prevent the onset of other pathologic conditions. The aim of this study is to examine the prevalence of HRT use in a sample of menopausal women and their experience with menopause and HRT. This study also investigates the knowledge of general practitioners (GPs) and gynecologists about HRT and its prescription. Materials and Methods: We conducted a cross-sectional population survey on 126 women of 50-59 years in an industrial city in the North of Italy, Vercelli (Novara), in Eastern Piedmont. We also presented a questionnaire on the topic to 54 medical doctors (GPs and gynecologists) of the same area. Results: The prevalence of HRT use in our sample was 11.9%. In total, a good percentage of the users affirmed to be satisfied with HRT. Additionally, a minority of women reported being ideally against the use of replacement hormones, were advised against using HRT by doctors, and did not use it because of the fear of side effects. We found a positive association between patient education, health care attitude, and HRT usage. A significant number of women knew about HRT from the media, and most of them were not informed by a health professional. Despite this, the interviewed doctors considered their knowledge about HRT as 'good' and would recommend HRT: only 5.6% would not prescribe it. Conclusions: Our results highlight the need for information about HRT among patients and health professionals, along with the need for more effective communication, evaluation, and suggestion of treatment.

Reproductive factors and cardiovascular health in post-menopausal women: a special focus on natural menopause.

Female-specific reproductive factors might contribute to increased risk of cardiovascular disease, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the relationships between reproductive factors and the LE8 score among post-menopause women in the United States. We enrolled 3223 post-menopause women from National Health and Nutrition Examination Survey (NHANES). CVH groups based on LE8 score were low (0-49), moderate (50-79), and high good CVH levels (80-100). Multivariate ordinal logistic regressions were applied to estimate the associations between reproductive factors and the LE8 score. In multivariate model, early menarche (OR: 0.69, 95 percent CI: 0.51-0.93) and early menopause (OR: 0.57, 95 percent CI: 0.43-0.77) were associated with LE8 score compared with normal menarche and menopause; Meanwhile, ages at menarche and menopause were positively correlated with LE8 score. The number of pregnancies and full-term pregnancies were negatively associated with LE8 (OR for per pregnancy increase and 95 percent CI, 0.93 (0.88, 0.98), 0.93 (0.87, 0.99), separately). Overall, natural menopausal women with early age at menarche and menopause, and a higher number of pregnancies may have a high risk of lower CVH, and need to focus on their CVH.

Menopause modified the association of blood pressure with osteoporosis among gender: a large-scale cross-sectional study.

Purpose: This study aimed to assess the potential association between blood pressure and osteoporosis in a rural population with limited resources. Existing evidence on this association is limited, particularly in such settings. Methods: Data from 7,689 participants in the Henan Rural Cohort study were analyzed. Four blood pressure indicators [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP)] were measured. The logistic regression model and restricted cubic spline plots were used to assess the relationship between blood pressure indicators and osteoporosis prevalence. Results: Positive trends were noted between blood pressure indicators and osteoporosis prevalence in the entire group and women (P trend < 0.05 for SBP, MAP, and PP). Women with higher SBP and PP exhibited elevated odds of osteoporosis compared with those with the lowest SBP and PP (ORs ranging from 1.15 to 1.5 for SBP and 1.06 to 1.83 for PP). No such associations were found in men. These relationships were only evident in postmenopausal women. Dose-response analysis confirmed these findings. Excluding participants taking hypertension medication did not alter the results. Conclusion: In resource-limited settings, higher SBP and PP are associated with the increased prevalence of osteoporosis in women, potentially influenced by menopause-related factors. This indicates that potential gender-based differences and social inequalities may affect bone health. Clinical trial registration: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) http://www.chictr.org.cn/showproj.aspx?proj=11375.

Association between breastfeeding duration and diabetes mellitus in menopausal women: a machine-learning analysis using population-based retrospective study.

BACKGROUND: Breastfeeding resets insulin resistance caused by pregnancy however, studies on the association between breastfeeding and diabetes mellitus (DM) have reported inconsistent results. Therefore, we aimed to investigate the risk of DM according to breastfeeding duration in large-scale population-based retrospective study. In addition, machine-learning prediction models for DM and hemoglobin A1c (HbA1c) were developed to further evaluate this association. METHODS: We used the Korean National Health and Nutrition Examination Surveys database, a nationwide and population-based health survey from 2010 to 2020. We included 15,946 postmenopausal women with a history of delivery, whom we divided into three groups according to the average breastfeeding duration: (1) no breastfeeding, (2) < 12 months breastfeeding, and (3) ≥ 12 months breastfeeding. Prediction models for DM and HbA1c were developed using an artificial neural network, decision tree, logistic regression, Naïve Bayes, random forest, and support vector machine. RESULTS: In total, 2248 (14.1%) women had DM and 14,402 (90.3%) had a history of breastfeeding. The prevalence of DM was the lowest in the < 12 breastfeeding group (no breastfeeding vs. < 12 months breastfeeding vs. ≥ 12 months breastfeeding; 161 [10.4%] vs. 362 [9.0%] vs. 1,725 [16.7%], p < 0.001). HbA1c levels were also the lowest in the < 12 breastfeeding group (HbA1c: no breastfeeding vs. < 12 months breastfeeding vs. ≥ 12 months breastfeeding; 5.9% vs. 5.9% vs. 6.1%, respectively, p < 0.001). After adjustment for covariates, the risk of DM was significantly increased in both, the no breastfeeding (adjusted odds ratio [aOR] 1.29; 95% CI 1.29, 1.62]) and ≥ 12 months of breastfeeding groups (aOR 1.18; 95% CI 1.01, 1.37) compared to that in the < 12 months breastfeeding group. The accuracy and the area under the receiver-operating-characteristic curve of the DM prediction model were 0.93 and 0.95, respectively. The average breastfeeding duration was ranked among the top 15 determinants of DM, which supported the strong association between breastfeeding duration and DM. This association was also observed in a prediction model for HbA1c. CONCLUSIONS: Women who did not breasted had a higher risk of developing DM than those who breastfed for up to 12 months.

Metabolome-wide Mendelian randomization for age at menarche and age at natural menopause.

BACKGROUND: The role of metabolism in the variation of age at menarche (AAM) and age at natural menopause (ANM) in the female population is not entirely known. We aimed to investigate the causal role of circulating metabolites in AAM and ANM using Mendelian randomization (MR). METHODS: We combined MR with genetic colocalization to investigate potential causal associations between 658 metabolites and AAM and between 684 metabolites and ANM. We extracted genetic instruments for our exposures from four genome-wide association studies (GWAS) on circulating metabolites and queried the effects of these variants on the outcomes in two large GWAS from the ReproGen consortium. Additionally, we assessed the mediating role of the body mass index (BMI) in these associations, identified metabolic pathways implicated in AAM and ANM, and sought validation for selected metabolites in the Avon Longitudinal Study of Parents and Children (ALSPAC). RESULTS: Our analysis identified 10 candidate metabolites for AAM, but none of them colocalized with AAM. For ANM, 76 metabolites were prioritized (FDR-adjusted MR P-value ≤ 0.05), with 17 colocalizing, primarily in the glycerophosphocholines class, including the omega-3 fatty acid and phosphatidylcholine (PC) categories. Pathway analyses and validation in ALSPAC mothers also highlighted the role of omega and polyunsaturated fatty acids levels in delaying age at menopause. CONCLUSIONS: Our study suggests that metabolites from the glycerophosphocholine and fatty acid families play a causal role in the timing of both menarche and menopause. This underscores the significance of specific metabolic pathways in the biology of female reproductive longevity.

The relationship between religious affiliation and menopause symptoms and attitudes in United States women.

OBJECTIVES: This study's aim is to examine patterns of menopause symptoms and attitudes among United States women from different religious affiliations. STUDY DESIGN: We used data from a national sample of midlife and older adults. For this analysis, we included only women who were postmenopausal or had undergone hysterectomy. We constructed univariate and multivariate logistic regression models to examine the relationship between religious affiliation and menopause symptoms and attitudes while adjusting for potential confounders. MAIN OUTCOME MEASURES: Menopause symptoms (hot flashes, pain in sexual interactions, pleasure in sexual interactions, trouble falling asleep) and attitudes (relief on periods stopping, regret on periods stopping, worry about becoming less attractive) measured by self-report on Likert scales. RESULTS: Across denominations, 47 % of women experienced hot flashes, 48 % experienced pain in sexual interactions, 95 % experienced pleasure, and 88 % had trouble falling asleep. Regarding attitudes towards menopause and aging, 62 % felt relief in their periods stopping, while 56 % expressed worry about becoming less attractive with aging. Baptist women were more likely to experience hot flashes and trouble falling asleep compared to Catholic women. However, when adjusted for smoking status, this relationship did not persist. Unaffiliated and Spiritual women were less likely to experience trouble falling asleep and more likely to report pleasure in sexual interactions compared to Catholic women. Spiritual women were significantly more likely to feel regret on periods stopping compared to Catholics. CONCLUSIONS: There is a relationship between religious affiliation and the menopause experience. These findings demonstrate the importance of considering social influences on women's health.

Weight gain during midlife: Does race/ethnicity influence risk?

Fears regarding weight gain and body changes commonly plague midlife women. The aim of this paper is to discuss the impact of weight gain and body changes on midlife women across various cultural backgrounds. Midlife weight gain in women is associated with age as opposed to menopausal status. Weight gain during midlife occurs across all cultural/ethnic groups; however, African Americans and Hispanic women exhibit higher rates of weight gain than their Caucasian counterparts. Although use of menopause hormone replacement therapy does not produce a clinical difference in weight gain, exercise decreases the risk of obesity in midlife women. Cultural differences in perception of body image exist. Recognizing these differences may help clinicians better address the weight concerns of women from diverse backgrounds. A shift in focus from weight goals to cardiometabolic risk reduction may help patients feel more successful and improve health outcomes.

Hormone therapy in women with benign breast disease - What little is known and suggestions for clinical implementation.

Benign breast disease encompasses a spectrum of lesions within the breast. While some lesions pose no increase in risk, others may elevate the likelihood of developing breast cancer by four- to five-fold. This necessitates a personalized approach to screening and lifestyle optimization for women. The menopausal transition is a critical time for the development of benign breast lesions. Increased detection can be attributed to the heightened precision and utilization of screening mammography, with or without the use of supplemental imaging. While it is widely acknowledged that combined hormone therapy involving estrogen and progesterone may elevate the risk of breast cancer, data from the Women's Health Initiative (WHI) indicates that estrogen-alone therapies may actually reduce the overall risk of cancer. Despite this general understanding, there is a notable gap in information regarding the impact of hormone therapy on the risk profile of women with specific benign breast lesions. This review comprehensively examines various benign breast lesions, delving into their pathophysiology and management. The goal is to enhance our understanding of when and how to judiciously prescribe hormone therapy, particularly in the context of specific benign breast conditions. By bridging this knowledge gap, the review provides valuable insights into optimizing healthcare strategies for women with benign breast disease, and offers a foundation for more informed decision-making regarding hormone therapy.

Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.