Healthy Postmenopausal Women Research Articles

Pre-Existing Metabolic Conditions Impair the Beneficial Effects of Estrogen on Memory and Cognition in Ovariectomized Mice

Loss of estrogen, as a result of menopause, has been associated with cognitive decline and memory loss. Intriguingly, studies conducted with postmenopausal healthy women suggest that hormone replacement therapy improves cognitive functions. In contrast, clinical data involving subjects with a wide range of health conditions indicate that the effect of estrogen treatment varies. In addition to the cognitive decline, postmenopausal women have an increased risk of developing metabolic disorders including obesity, insulin resistance, and diabetes. In this study, we tested the hypothesis that pre-existing metabolic conditions reduce the beneficial effects of estradiol treatment and are responsible for the conflicting findings in cognitive functions after menopause. Female, seven-month-old C57BL/6J mice were fed with either a high-fat diet (HFD, BioServ #F3282) or a control diet (LFD, BioServ #F4031) for 10 to 14 weeks, then ovariectomized (OVX). In a randomized manner, mice received a silastic tube implant containing either 17β-estradiol (E2) or vehicle (VEH, cholesterol) and stayed on their respective diets. Body composition and metabolic parameters were measured in the four groups (HFD+VEH, HFD+E2, LFD+VEH, LFD+E2) to assess metabolic status, and novel object recognition test was performed to assess memory and cognition. Before OVX, HFD fed mice had significantly increased body weight, fat mass, basal blood glucose and insulin levels compared to mice fed with LFD. After OVX, LFD-VEH mice developed obesity and had elevated blood glucose and insulin levels, whereas E2 treatment prevented the metabolic changes. Interestingly, HFD-VEH mice had a reduction in fat mass after OVX, which was further decreased with E2 treatment. Overall, mice treated with E2 had lower body weight, fat mass, blood glucose and insulin levels compared to VEH treated mice regardless of their diet, and HFD fed mice had a higher body weight than mice fed the LFD, irrespective of their treatment. The novel object recognition test revealed that LFD-E2 mice spent significantly more time exploring the novel object than LFD-VEH mice. In contrast, there was no difference in exploration time between HFD-VEH and HFD-E2 treated mice. These preliminary results suggest that 1) E2 treatment may be beneficial to prevent the development of metabolic changes and improve cognitive function in LFD fed mice; 2) OVX alone did not worsen the metabolic status of diet-induced obese mice; 3) E2 treatment partially improved the metabolic status of HFD fed mice by decreasing fat mass, blood glucose and insulin levels; and 4) E2 treatment did not improve memory and cognition of HFD fed mice. Source of funding: P01AG071746 8456. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Central and peripheral cardiovascular responses after acute dietary nitrate supplementation in post-menopausal women

The transition to menopause is accompanied by augmented cardiovascular disease risk, partially attributed to reduced nitric oxide (NO) bioavailability. Despite a lower arterial stiffness than men, postmenopausal women are susceptible to increased aortic pulsatile hemodynamic load because of greater pressure wave reflection and vascular dysfunction. Increasing bioavailable NO with dietary nitrate has shown promise to reduce aortic (aSBP) and brachial (bSBP) systolic pressure healthy postmenopausal women. However, there are limited reports comparing hypertensive (HTN) and normotensive (NTN) postmenopausal women regarding wave separation analysis and vascular function following dietary nitrate supplementation. This study investigated if acute dietary nitrate supplementation would improve aortic hemodynamics, wave reflection characteristics, vascular stiffness, and vasodilatory function. We hypothesized that dietary nitrate would lower pulse wave velocity in hypertensives, lower aortic and brachial blood pressures and forward and backward wave magnitude and increase microvascular, but not macrovascular function in both groups. Fourteen postmenopausal women (n=7 HTN; n=7 NTN) participated in a two-day randomized crossover study design with dietary nitrate (nitrate rich, NR) or a placebo control (NP). Central and peripheral hemodynamics and carotid-femoral pulse wave velocity (cfPWV) were performed with a SphygmoCOR Excel, simultaneous resting macro- and- microvascular function was assessed using flow-mediated vasodilation (FMD) and post occlusive reactive hyperemia (PORH) using near-infrared spectroscopy. aSBP was reduced significantly following NR supplement within groups (HTN: NP 126±2 NR 120±1mmHg) and NTN group (NP 110± 1 NR 104±3mmHg p<0.05). Forward pulse height HTN (NP 29±1.4 NR 26.3±1.4mmHg) NTN (NP 25.6±0.9 NR 24±2.7mmHg) and reflected pulse height HTN (NP 18.2±0.08 NR 17.2±0.4mmHg) NTN (NP 17.7±0.2 NR 15.7±1.07mmHg) were not different. cfPWV was faster in the HTN group and slowed with a NR supplement (HTN: NP 8.2±0.29 NR 7.4±0.31m/s; NTN NP 7.1±0.23 NR 6.6±0.62m/s p<0.05). A significant interaction for %FMD was found (HTN: NP 7.3±0.8 NR 6.2±0.8%; NTN NP 6.6±0.7 NR 9.4±0.7%). Further, we found no difference in the NIRS derived microvascular function measurements (HTN: NP 1.9±0.2 NR 1.7±0.3%/s; NTN NP 1.6±0.1 NR 1.4±0.2%/s p>0.05). These data indicate that dietary nitrate consumption led to a substantial reduction in aortic hemodynamics and reduced pulse wave velocity regardless of hypertension status. Interestingly, macrovascular, but not microvascular vasodilatory function was improved in the NTN women only. Dietary nitrate supplementation appears to have differential effects when considering HTN and NTN postmenopausal women. Supported with funds from The University of Wisconsin-La Crosse RSEL graduate grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dampened circadian amplitude of EEG power in women after menopause.

Postmenopausal women are at high risk of developing sleep-wake disturbances. We previously reported dampened circadian rhythms of melatonin, alertness and sleep in postmenopausal compared with young women. The present study aims to further explore electroencephalography power spectral changes in the sleep of postmenopausal women. Eight healthy postmenopausal women were compared with 12 healthy, naturally ovulating, young women in their mid-follicular phase. Participants followed a regular 8-hr sleep schedule for ≥ 2 weeks prior to laboratory entry. The laboratory visit included an 8-hr baseline sleep period followed by an ultradian sleep-wake cycle procedure, consisting of alternating 1-hr wake periods and nap opportunities. Electroencephalography power spectral analysis was performed on non-rapid eye movement sleep obtained over a 48-hr period. The baseline nocturnal sleep of postmenopausal women comprised lower power within delta and sigma, and higher power within alpha bands compared with that of younger women. During nighttime naps of the ultradian sleep-wake cycle procedure, lower power within delta and sigma, and higher power within beta bands were observed in postmenopausal women. During the ultradian sleep-wake cycle procedure, postmenopausal women presented lower power of delta, theta and sigma (14-15 Hz), undetectable rhythms of delta and theta, and a dampened or undetectable rhythm of sigma (12-15 Hz) power compared with younger women. Our results support the hypothesis of a dampened circadian variation of sleep microstructure in healthy-sleeping postmenopausal women. Circadian changes with aging are potential mechanisms for increased susceptibility to develop sleep disturbances; however, further research is needed to clarify their clinical implications and contribution to insomnia.

The Effectiveness of a Lactobacilli-Based Probiotic Food Supplement on Bone Mineral Density and Bone Metabolism in Australian Early Postmenopausal Women: Protocol for a Double-Blind Randomized Placebo-Controlled Trial.

Osteoporosis affects one in three women over the age of 50 and results in fragility fractures. Oestrogen deficiency during and after menopause exacerbates bone loss, accounting for higher prevalence of fragility fractures in women. The gut microbiota (GM) has been proposed as a key regulator of bone health, as it performs vital functions such as immune regulation and biosynthesis of vitamins. Therefore, GM modulation via probiotic supplementation has been proposed as a target for potential therapeutic intervention to reduce bone loss. While promising results have been observed in mouse model studies, translation into human trials is limited. Here, we present the study protocol for a double-blind randomized controlled trial that aims to examine the effectiveness of three lactobacilli strains on volumetric bone mineral density (vBMD), trabecular, and cortical microstructure, as measured using High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The trial will randomize 124 healthy early postmenopausal women (up to 8 years from menopause) to receive either probiotic or placebo administered once daily for 12 months. Secondary outcomes will investigate the probiotics' effects on areal BMD and specific mechanistic biomarkers, including bone metabolism and inflammatory markers. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12621000810819).

Differences in dietary intake in early postmenopausal women with different levels of areal and volumetric bone mineral density: a cross-sectional analysis of baseline data from an intervention study

Osteoporosis is a degenerative disease of the bone. The rate of bone loss is accelerated during the first postmenopausal years in women which results in their disproportionate prevalence of osteoporosis(2). Some of the factors contributing to the development and maintenance of bone mineral density (BMD) relate to diet, particularly the intake of protein, calcium and other micronutrients that play a crucial role in bone composition(3). The most common method of measuring BMD is dual-energy X-ray absorptiometry (DXA) which generates a two-dimensional image of the scan site (typically spine, hip and/or forearm) to determine areal BMD (aBMD). However, new methods have recently emerged, including High Resolution peripheral Quantitative Computed Tomography (HRpQCT), that offer more accurate three-dimensional measurements of volumetric BMD (vBMD) and microstructure of distal tibia and radius(4). The aim of this study was to examine the differences in the dietary intake of nutrients that represent organic or inorganic components of the bone, in early postmenopausal women with different spine aBMD and tibia and radius vBMD levels. One hundred and fourteen healthy early postmenopausal women with a lumbar spine or total hip BMD T score > −2.5 (measured by DXA) were recruited as part of a larger interventional study. Dietary intake was recorded using a 297-point self-reported validated food frequency questionnaire(5) for assessing the intake of energy, macro and micronutrients. Physical activity was self-reported using the validated Active Australia Questionnaire. Years since menopause were self-reported. DXA and HRpQCT scans measured L1-L4 spine, proximal femur aBMD, and distal tibia and radius vBMD respectively. Non-parametric statistical tests examined differences in dietary intake and physical activity levels between women at different levels of aBMD and vBMD. Data reported as median and interquartile ranges. There were no significant differences observed in the total sample between tertiles of aBMD and vBMD, regarding nutrient intake. However, for women with less than 3 years since menopause (i.e., the time-period of accelerated bone loss), lower dietary intakes of energy [8,658(3,324) vs 10,068(3,688) kJ/day; p = 0.047], protein [94(29) vs 103(32) g/day; (p = 0.044)], sodium [1,927(992) vs 2,625(2,185) mg/d; (p = 0.044)], potassium [4,064(1,373) vs 5,121(2,377) mg/d; (p = 0.041)], calcium [969(325) vs 1,214(652) mg/d; (p = 0.028)] and zinc [10(3) vs 12(4) mg/d; (p = 0.005)] were observed for women with osteopenia (−1< L1-L4 aBMD T-score <2.5) compared to those with normal L1-L4 aBMD (i.e., T-score > −1). No significant differences were observed for women with more than 3 years since menopause, with the only exception of alcohol intake (p = 0.033), which was found to be lower in women with osteopenia compared to those with normal aBMD. These findings highlight the importance of targeting osteopenic women within the first 3 years following menopause as candidates for tailored dietary intervention programs for preventing osteoporosis.

401 Detecting Hypofibrinolysis in Clinical Coagulation Testing

OBJECTIVES/GOALS: The goal of this study is twofold: To develop a method for an ex vivo hypofibrinolytic control and second to analyze patterns in standard and recently developed clinical coagulation assays for the detection of hypofibrinolytic states. METHODS/STUDY POPULATION: We analyzed blood samples from healthy patients first under normal conditions and then laced with human recombinant PAI-1 under three different concentrations. We then analyzed both samples using standard clinical assays (PT, aPTT, D-dimer, Fibrinogen), thromboelastography point-of-care tests (Hemosoncs- Quantra system), and with research assays of clot size and aggregation. Our previous research of diagnostic errors showed the patient group with the highest overall risk of these non-identifiable thrombotic complications was post-menopausal women with chronic diseases. We therefore focused our patient population to healthy post-menopausal women who were not using hormone replacement therapy. RESULTS/ANTICIPATED RESULTS: Research assays showed PAI-1 significantly increased clot size and aggregation. Preliminary results of clinical assays showed no detectable difference in hypofibrinolytic samples at any concentration. We anticipate ongoing testing will show similar results. Results on Quantra tests showed much larger differences between control and hypofibrinolysis samples, and we anticipate ongoing testing will achieving statistical significance. It is still unknown whether the mean value for hypofibrinolysis samples on the Quantra Clot Stability assay will be outside of the “normal” reference range. We theorize that this may be due to hypofibrinolytic changes in the overall structure and core density of the clots. DISCUSSION/SIGNIFICANCE: Cellular stress stimulates a concomitant activation of inflammation and coagulation, including decreased fibrinolysis. Unfortunately, current clinical assays do not assess clot breakdown. This connection would account for the increased rate of thrombosis in patients with chronic inflammation without detectable results on clinical tests.

The effect of pre- and probiotic supplementation on inflammatory markers in postmenopausal women

Chronic inflammation is linked with several deleterious diseases, including cardiovascular disease, obesity, diabetes mellitus, irritable bowel disease, and osteoporosis (1,2). Post-menopausal women are at a heightened risk of developing these diseases due to the remission of oestrogen, further amplifying a pro-inflammatory state (3,4). This study aimed to critically examine the combined effect of pre- and probiotic supplementation (synbiotics) and exercise in the form of ≥7,000 steps per day on inflammatory markers hs- CRP, IL-1β, IL-6, IL-8, IL-10, INF-γ and TNF- α in sedentary post-menopausal women. Eighty-seven healthy post-menopausal women were allocated to receive either a synbiotic supplement or placebo for 12 weeks. Participants’ demographics and physical activity levels were determined using questionnaires, and their diet was assessed using self-reported 3-day diet records. Body composition measures of height, weight and BMI were measured at baseline, while total body mass, lean body mass, total fat mass and total body fat percentage at baseline and week 12 using dual-energy X-ray absorptiometry. Fasted venous blood samples were collected to analyse inflammatory status before and after the intervention. Statistical analysis was performed using SPSS version 24, where outcome variables with multiple time points, were analysed using repeated measures ANOVA with the model, including time (baseline vs 12 weeks), intervention group (placebo vs synbiotic), and their interaction as fixed effects. The results showed no significant differences between the intervention group’s demographics, physical activity levels, and dietary intake (p > 0.05). The 12-week study duration (time) was found to have had a statistically significant effect on lowering hs-CRP (p <0.018), IL-8 (p <0.001), IFN-γ (p <0.001), TNF-α (p <0.001) and increasing IL-6 (p <0.001) and IL-10 (p <0.001) in both groups. However, the observed decrease in IL-1β (p <0.348) over time was not significant. The intervention type (synbiotic or placebo) significantly impacted IL-10 (p < 0.003). No significant interactions between time and group were observed across all other inflammatory markers (p > 0.05). The study duration increased total lean body mass (p <0.015) and decreased total body fat percentage (p <0.022) in both the placebo and synbiotic groups. At the same time, the intervention type (synbiotic or placebo) had no effect on total lean body mass, total fat mass, total body mass and percentage body fat in both groups (p > 0.05). The current study showed no notable differences between the placebo and synbiotic groups suggesting synbiotic supplementation is likely ineffective at reducing chronic inflammation in overweight, sedentary post-menopausal women living in New Zealand. However, future studies are needed to confirm these findings. Additionally, studies should investigate the effects of exercise and synbiotic supplementation separately in this population.

Effect of Hormone Therapy on Lipoprotein Subfractions in Early and Late Postmenopausal Women.

The Early vs Late Intervention Trial with Estradiol (ELITE) showed that hormone therapy (HT) reduced atherosclerosis progression among early but not late postmenopausal women (PMW). Determined by time-since-menopause (1) HT effects on lipids and lipoprotein particle subfractions (LPs), (2) associations of estradiol (E2) level with lipids and LPs, (3) associations of lipids and LPs with atherosclerosis progression. Randomized controlled trial stratified by time-since-menopause. Academic institution. Healthy postmenopausal women. Oral E2 with/without sequential vaginal progesterone. Standard lipids and 21 LPs quantitated by ion mobility every 6 months. Among 562 PMW (240 early, 322 late), HT significantly increased total triglycerides (TG), high-density lipoprotein (HDL) cholesterol, small low-density lipoproteins (LDL), large HDL, and TG/C ratio in LDL and HDL and decreased LDL-cholesterol, total very low density lipoproteins (VLDL), small VLDL, intermediate-density lipoproteins, large LDL, and LDL peak diameter. HT showed no lipid or LP differences between time-since-menopause. Associations of E2 level with lipids and LPs explained the HT effects. Despite the nonsignificant P interaction by time-since-menopause, we observed that very small LDL and total HDL LPs were associated with atherosclerosis progression in late PMW. HT effects on standard lipids and LPs are consistent with the literature. HT has similar effect on lipids and LPs in early and late PMW. Novel findings include discordant effects of HT on TG and VLDL particles, which can be explained by increased catabolism of atherogenic remnants of TG-rich lipoproteins. Our findings extend the well-known HT effects on standard lipids and LPs that may contribute to the beneficial effects on atherosclerosis progression in PMW.

Spontaneous fractures in healthy postmenopausal women aged 55+ years in two health centers: Laquintinie Hospital and General Hospital, Douala, Cameroon

Background: Women in their old age are facing some health issues due to physiological changes. It was observed many cases of osteoporosis during menopause. At that stage of their life, women undergo ovaries atrophy caused by hormonal imbalance. Estrogen deficiency is a leading cause of osteoporosis in postmenopausal women. That is why at menopause when its level drops women have fragile bones and are prone to fractures of many kinds. Fractures are associated with a high risk of morbidity which is why we aimed to identify and characterize the state of fractures in older women during menopause in our country. Method: A survey was performed at the orthopedic-traumatology and rheumatology unit of 2 different health centers: Laquintinie Hospital of Douala and Douala General Hospital (DGH). Files of postmenopausal women admitted for fracture were screened. The data were analyzed by SPSS and statistical significance was considered when P-value < 0.05. Results: 643 files of postmenopausal women admitted for fractures were analyzed. Results showed that 29% (186/643) of women at menopause aged above 55 years old had spontaneous fractures. The mean age was 71.89 years, ranging from 55 to 119 years. Falls and domestic accidents were the top two most represented causes (38.2 and 31.7 % respectively). Among those fractures, 70% happened after minimal trauma. The wrist was the favorite anatomical site for patients aged ranged between 55-64 years. As for UEF (Upper end of the femur) fracture, it increased in an age-related manner. Absence of trauma was observed the less in population aged between 55 and 64 years (11.5% ; P<0.001); and it was highest in women aged 85+ years (64%). Conclusion: Postmenopausal women in our population have disabilities due to spontaneous fractures which impact negatively their quality of life. We should spread awareness among women before they reach menopause to take suitable measures to reduce the incidence of fractures and related morbidity at a certain age.

Resistance training effects on healthy postmenopausal women: a systematic review with meta-analysis

The aim of this systematic review with meta-analysis was to evaluate the effects of resistance training on physical fitness, physiological variables and body composition of postmenopausal women. The present systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and was registered in PROSPERO. A total of 12 studies were included. The literature search was performed in PubMed, Web of Science and EBSCO. Randomized control trials were included. Two blinded investigators performed the search, study selection and data collection, and assessed the quality and risk of bias. A random-effects model was used for all analyses. Compared to the control group, resistance training produced a significant improvement in maximal oxygen volume (standardized mean difference [SMD] = 2.32, p < 0.001), lower extremity strength (SMD = 4.70, p < 0.001) and upper extremity strength (SMD = 7.42, p < 0.001). The results obtained in the systematic review and meta-analysis confirm the benefits of resistance training on physical fitness in postmenopausal women, although there is more debate regarding its influence on bone mineral density, and anthropometric and derived variables. This work provides a solid starting point for promoting resistance training at a frequency of 3 days per week, in 60-min sessions, with the aim of improving parameters directly related to quality of life, functionality and disease prevention of postmenopausal women.

Effect of Unfermented Soy Product Consumption on Blood Lipids in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundClinical studies have reported the beneficial effects of unfermented soy product consumption on blood lipids in various populations. However, contradictory results have been reported regarding the influence of unfermented soy product consumption on blood lipids in postmenopausal women. ObjectiveThe aim of this systematic review and meta-analysis was to evaluate the effects of diets with unfermented soy products compared with diets without unfermented soy products on blood lipids in postmenopausal women. MethodsThe Cochrane Library, PubMed, Scopus, Web of Science, and Embase electronic databases were searched for eligible randomized controlled trials (RCTs) published up to February 21, 2023. RCTs were included if they were published in English and investigated the effect of unfermented soy product consumption on blood lipids in postmenopausal women who had discontinued hormone replacement therapy at least 3 months before randomization. A random-effects model was used to calculate the overall effect size of the mean difference (MD) and 95% CI. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool for Randomized Trials, version 2. ResultsTwenty-nine RCTs involving 2,457 participants were included. The results showed that, compared with the control group that did not consume unfermented soy products, consumption of unfermented soy products significantly reduced total cholesterol (TC) (MD, −9.46 mg/dL [to convert mg/dL cholesterol to mmol/L, multiply mg/dL by 0.0259; to convert mmol/L cholesterol to mg/dL, multiply by 38.7]; 95% CI −15.04 to −3.89 mg/dL; P = .001) and triglycerides (TGs) (MD, −10.86 mg/dL [to convert mg/dL TGs to mmol/L, multiply mg/dL by 0.0113; to convert mmol/L TGs to mg/dL, multiply mmol/L by 88.6]; 95% CI −19.70 to −2.02 mg/dL; P = .016), while significantly increasing high-density lipoprotein cholesterol (MD, 2.32 mg/dL; 95% CI 0.87 to 3.76 mg/dL; P = .002) in postmenopausal women, but had no significant effect on low-density lipoprotein cholesterol (MD, −4.55 mg/dL; 95% CI −10.90 to 1.80 mg/dL; P = .160). Results of soy preparation subgroup analysis showed that soy isolate protein significantly reduced TC and soy protein–containing isoflavones significantly reduced TC and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Furthermore, unfermented soy product consumption significantly reduced TC, low-density lipoprotein cholesterol, and TG levels in postmenopausal women with lipid disorders and TGs in healthy postmenopausal women. ConclusionsThe results showed that unfermented soy product consumption reduced TC and TG levels significantly, and increased high-density lipoprotein cholesterol levels in postmenopausal women. The findings of this review contribute to the evidence-base for dietary management of blood lipids in postmenopausal women.

Plasma microRNA signature associated with skeletal muscle wasting in post-menopausal osteoporotic women.

Skeletal muscle mass wasting almost invariably accompanies bone loss in elderly, and the coexistence of these two conditions depends on the tight endocrine crosstalk existing between the two organs, other than the biomechanical coupling. Since the current diagnostics limitation in this field, and given the progressive population aging, more effective tools are needed. The aim of this study was to identify circulating microRNAs (miRNAs) as potential biomarkers for muscle mass wasting in post-menopausal osteoporotic women. One hundred seventy-nine miRNAs were assayed by quantitative real-time polymerase chain reaction in plasma samples from 28 otherwise healthy post-menopausal osteoporotic women (73.4±6.6years old). The cohort was divided in tertiles based on appendicular skeletal muscle mass index (ASMMI) to better highlight the differences on skeletal muscle mass (first tertile: n=9, ASMMI=4.88±0.40kg·m-2; second tertile: n=10, ASMMI=5.73±0.23kg·m-2; third tertile: n=9, ASMMI=6.40±0.22kg·m-2). Receiver operating characteristic (ROC) curves were calculated to estimate the diagnostic potential of miRNAs. miRNAs displaying a statistically significant fold change≥±1.5 and area under the curve (AUC)>0.800 (P<0.05) between the first and third tertiles were considered. A linear regression model was applied to estimate the association between miRNA expression and ASMMI in the whole population, adjusting for body mass index, age, total fat (measured by total-body dual-energy X-ray absorptiometry [DXA]) and bone mineral density (measured by femur DXA). Circulating levels of adipo-myokines were evaluated by bead-based immunofluorescent assays and enzyme-linked immunosorbent assays. Five miRNAs (hsa-miR-221-3p, hsa-miR-374b-5p, hsa-miR-146a-5p, hsa-miR-126-5p and hsa-miR-425-5p) resulted down-regulated and two miRNAs (hsa-miR-145-5p and hsa-miR-25-3p) were up-regulated in the first tertile (relative-low ASMMI) compared with the third tertile (relative-high ASMMI) (fold change≥±1.5; P-value<0.05). All the corresponding ROC curves had AUC>0.8 (P<0.05). Two signatures hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p showed the highest AUC, 0.914 (sensitivity=77.78%; specificity=100.00%) and 0.901 (sensitivity=88.89%; specificity=100.00%), respectively. In this study, we identified, for the first time, two miRNA signatures, hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p, specifically associated with muscle mass wasting in post-menopausal osteoporotic women.

A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors

Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.

Trop T, hand grip strength and waist circumference as markers of sarcopenic obesity in postmenopausal women: An analytical cross-sectional study

Objectives: Sarcopenic obesity is defined as age-associated histological changes and adiposity in muscles that impair muscle function. Asian Working Group for Sarcopenia suggested hand grip strength (HGS) and gait speed for screening sarcopenia. Troponin is a putative biomarker of muscle health. The study aims to evaluate Trop T, HGS, and waist circumference (WC) as markers of sarcopenic obesity in postmenopausal women. Materials and Methods: An analytical cross-sectional study was conducted in healthy postmenopausal women. Anthropometric measurements, HGS, and gait speed were documented. Postmenopausal women were identified as sarcopenic obesity with the following criteria: (a) The cut-points for weak handgrip strength (kg) for women as &lt;18 in Asians (b) WC ≥85 cm in women. Total cholesterol, triglycerides, high-density lipoprotein (HDLc), low-density lipoprotein (LDLc), and high sensitive troponin T levels were estimated in the automated biochemistry analyser. Results: About 33% sarcopenic obesity was observed in postmenopausal women aged 56 to 60 years. WC (93 cm) and body mass index (29.64) were increased in sarcopenic obese. Decreased HGS (9.44 kg) and increased gait speed (13.62 s) were observed in sarcopenic obese as compared to non-sarcopenic obese women. Increased troponin T (0.068 ng/mL), small dense LDLc (mmol/L), LDLc, non-HDLc, and decreased HDLc were observed in sarcopenic obese postmenopausal women. Receiver’s operating characteristic curve: sensitivity of waist circumference, HGS, gait, and troponin T were 97% (area under the curve [AUC] 0.76), 83% (AUC 0.84), 82% (AUC 0.76) and 67% (AUC 0.77), respectively. Conclusion: Measurement of waist circumference, hand grip strength, and gait are diagnostic tools of sarcopenic obesity that divulges the quality of postmenopausal life.

Normal Risk Ovarian Screening Study: 21-Year Update.

The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually. Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV. While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy.

Effect of estradiol with or without micronized progesterone on cholinergic-related cognitive performance in postmenopausal women.

Women are at a higher risk of developing Alzheimer's disease (AD), and the decline in estrogens post-menopause is thought of as a factor increasing this risk. Estradiol (E2) is important in supporting cholinergic neuronal integrity, and cholinergic functioning may be negatively impacted following the loss of E2 post-menopause. The use of exogenous E2 has been observed to enhance cholinergically mediated cognitive performance in healthy post-menopausal women, which indicates a potentially protective mechanism. However, E2 is often co-administered with progestin or progesterone to prevent endometrial proliferation. Progesterone/progestins have previously been shown to have a detrimental effect on E2-mediated biological and cognitive effects mediated by cholinergic systems in preclinical models, therefore the present study aimed to assess whether progesterone would modify the effect of E2 to influence cognition during cholinergic blockade. Twenty participants completed 3-months of oral E2 treatment with micronized progesterone (mPRO) or with placebo (PLC) in a repeated-measures within-subjects crossover design, in which they also completed five anticholinergic challenge days per hormone treatment condition. During the challenge participants were administered low or high doses of the nicotinic cholinergic antagonist mecamylamine, the muscarinic cholinergic antagonist scopolamine, or placebo. Following drug administration participants performed cognitive tests sensitive to cholinergic tone, assessing attention, episodic memory, and working memory. Significant decrements were found on some tasks when participants were taking E2+mPRO compared to E2 alone. Specifically, under more challenging task conditions and larger anticholinergic doses, participants showed poorer performance on the Critical Flicker Fusion task and the Stroop test and responded more conservatively on the N-back working memory task. Other tasks showed no differences between treatments under cholinergic blockade. The findings show that mPRO when taken in concert with E2, was detrimental to effortful cognitive performance, in the presence of cholinergic blockade. These results are important for assessing the impact of combined postmenopausal hormone treatment on cognitive performance that is dependent on cholinergic functioning after menopause.

Effects of a high-protein, low-glycemic-index diet on body weight and waist circumference in late postmenopausal women: a randomized controlled trial.

To describe the secondary outcomes (weight loss, waist circumference [WC], and glycolipid profile) of a previous randomized controlled trial designed to investigate the impact of a high-protein, low-glycemic-index (GI) diet on lean body mass in late postmenopausal women. A total of 26 healthy women aged ≥ 65 years and with a mean body mass index (BMI) of 26.1 ± 3.5 kg/m2 were randomly assigned to follow a low-GI diet (GI < 55) with protein consumption at the current recommended dietary allowance (RDA, 0.8 g/kg body weight) or twice the RDA (2RDA, 1.6 g/kg body weight). Changes in body weight, BMI, WC, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, and triglycerides were assessed at 3- and 6-month of follow-up in all participants. An intention-to-treat analysis was performed using a linear mixed model. Weight loss (mean change -1.7 kg, 95% confidence interval [CI] -2.8 to -0.5 kg, p = 0.004) was observed at 6 months, with no significant difference between the RDA and 2RDA groups. An overall significant WC decrease was observed at 6 months in all participants (mean change -3.8 cm, 95% CI -5.5 to -2.1 cm, p < 0.001), with no differences between groups. The glycolipid profile remained unchanged after 6 months of dietary intervention. Increasing protein intake did not lead to greater weight loss or reduction in WC in a sample of healthy postmenopausal women following a low-GI diet for 6 months.

Bone mineral density in the various regions of the skeleton in women with subclinical hypothyroidism: the effect of biological factors, bone turnover markers and physical activity

Abstract Study aim: This cross-sectional study examined the relationship between biological factors, physical activity (PA), bone turnover markers (BTMs) and bone mineral density (BMD) in women with subclinical hypothyroidism (SCH) and healthy. Material and methods: The study included 135 women. Bone parameters were measured by the densitometry. Calcium, phosphorus, osteocalcin (OC), total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), vitamin D and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were measured in blood serum. PA were evaluated by metabolic equivalent of task (MET). Results: Women with SCH had lower BMD in hip and lumbar spine, calcium, vitamin D and higher values of ICTP than the healthy group. In women with SCH, the affecting BMD in the femoral neck were ICTP (µg/l), (η² = 0.083), and also 25(OH)D (ng/ml), (η² = 0.080) and PA level (I/S), (η² = 0.115). BMD in the spine was affected by PA level (I/S), (η² = 0.173). The parameters affecting BMC in the femoral neck were 25(OH)D (ng/ml), (η² = 0.073). In all women sufficient levels of PA determined higher BMD. Conclusions: PA and BTMs significantly determine BMD levels. PA can be an important area of rehabilitation and physical therapy as an available measure to counteract BMD loss in postmenopausal healthy women and those with SCH.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. These included FSFI and low sexual function scores as well as measures of PWV and FMD. Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Hair and Serum Trace Element and Mineral Levels Profiles in Women with Premenopausal and Postmenopausal Osteoporosis.

The objective of the present study was to evaluate serum and hair trace element and mineral levels in women with osteoporosis, as well as to estimate the impact of menopausal status on the profile of trace element and mineral status in women with osteoporosis. 207 women with diagnosed osteoporosis 22-85 years-of-age, and 197 healthy women of the respective age participated in the present study. Analysis of the levels of mineral and trace element in hair and serum samples was performed by inductively-coupled plasma mass-spectrometry (ICP-MS). Women with osteoporosis were characterized by significantly lower hair Ca, Mg, Co, I, Li, and Mn levels, as well as serum Ca, Mg, Co, Fe, V, and Zn concentrations compared to women in the control group. After additional grouping according to menopausal status, the lowest hair Ca and Mg content was observed in postmenopausal osteoporotic women, whereas serum Ca and Mg concentrations were the lowest in premenopausal osteoporotic women. Hair Co, Mn, and Zn levels in postmenopausal osteoporotic women were lower than in healthy postmenopausal women. The lowest circulating Zn levels were observed in osteoporotic postmenopausal women. Taken together, decreased hair and serum levels in osteoporotic women are indicative of increased risk of Ca, Mg, Co, and Zn deficiency in women with osteoporosis. In turn, alterations in hair trace element and mineral levels in osteoporosis are more profound in postmenopausal women. Hypothetically, improvement in trace element and mineral metabolism especially in postmenopausal women may be considered as a potential strategy for mitigating osteoporosis.