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Objective: Frailty may be increased by menopause. Physical activity has been proposed to reduce frailty, but poor adherence and cost limit effectiveness. We aimed to investigate both the effectiveness against the frailty burden and the adherence rate of a multicomponent physical activity scheme partially managed by the participating women themselves., Methods: Prospective controlled study consisting of a twice-weekly group physical activity scheme divided into two consecutive periods, one supervised by a health professional (12 wk) and the other supervised by the women themselves (36 wk). Group cohesion and mutual support during the patient-only period were aided by social networking via smartphones. Community-dwelling postmenopausal women were divided into a physical activity group (PAG = 126) and a usual activity control group (UAG = 126), both assessed at baseline and at the end of the study. Participants self-assigned to one of the two study arms., Results: Overall, women in the PAG were more likely to improve their frailty status (60.2% vs 42.6%, P < 0.05). The frailty reversal rate from prefrail to robust was significantly higher in the PAG than in the UAG (34.04 vs 8.00%, P < 0.05). Logistic regression confirmed that women in the PAG were more likely to improve their frailty phenotype (odds ratio [OR], 9.12; 95% confidence interval [CI], 3.45-31.52; P < 0.001). Adherence, defined by participants attending 75% of sessions, was attained by 56.35% of women at 48 wk., Conclusion: A physical activity scheme implemented to improve frailty proved effective and attained acceptable adherence. Conditions in the peer-supervised 36-wk phase may increase sustainability., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2024 by The Menopause Society.)

Objective: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ER α and ER β genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women., Methods: A cross-sectional study was performed in which we selected five SNPs, three in the ER α gene and two in the ER β . Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables., Results: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ER α gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index ( p  = 0.012), number of comorbidities (0 vs. ≥2, p  = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p  = 0.036) and of childbirths (one vs. ≥3, p  = 0.008), were independently related to frailty., Conclusion: The five SNPs of the ER α and ER β genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Background: Dynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area., Aim: To analyze the association between genetic variants of the vitamin D receptor gene and dynapenia in a cohort of community-dwelling postmenopausal women., Methods: We performed a cross-sectional study of 463 women in a university hospital. Grip strength was used as an indicator of dynapenia. Differences in grip strength among single nucleotide polymorphisms rs11568820 and rs2228570 genotypes of the vitamin D receptor gene were assessed after adjusting for confounding variables, and the percentage of phenotypic variance was estimated by linear regression., Results: Dynapenia (grip strength <20 kg) was diagnosed in 178 of the women (38.45 %). A difference in grip strength, corresponding to variants of the vitamin D receptor gene single nucleotide polymorphism rs11568820, was found when using an additive model of inheritance, with lower grip strength for the TT genotype (ANOVA, p = 0.030, close to the 0.025 significance level determined by Bonferroni correction). Assuming a recessive inheritance model for allele T, the between-group difference in grip strength was significant (TT = 19.79 ± 3.10 kg vs. CC/CT = 21.58 ± 3.49 kg, p = 0.008) after adjusting for age, body mass index, comorbidities, and sociodemographic variables. More women with dynapenia had the TT genotype (60.71 %) than the CC or CT genotype (37.01 %) (p = 0.012)., Conclusion: This study demonstrates that the TT genotype of the rs11568820 SNP of the vitamin D receptor gene was associated with decreased grip strength in community-dwelling postmenopausal women., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Abstract: There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and β have not been investigated.We performed a crossed-sectional study of 91 women in a university hospital. We used a double approach in which, in addition to the measurement of estradiol levels by ultrasensitive methods, genetic variants (SNPs) associated with differing expression of the ER α and β genes were assessed. Multivariable analysis was used to examine the association of candidate factors with the value of IMT and plaque detection at both the carotid wall and the sinus.A genotype combination translating reduced gene expression of the ERβ was directly associated with IMT at both the carotid wall (P = .001) and the sinus (P = .002). Other predictors of IMT were the levels of glucose, positively associated with IMT at both the carotid wall (P < .001) and the sinus (P = .001), age positively associated with IMT at the sinus (P = .003), and levels of vitamin D, positively associated with IMT at the carotid wall (P = .04).Poorer estrogenic impact, as concordant with a SNP variant imposing reduced expression of the ERβ, was directly associated with IMT at both the carotid wall and the sinus. Glucose level, vitamin D only for the carotid wall, and age only for the sinus, also emerged as independent factors in the IMT variance., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Experimental studies suggest that lipids affect bone metabolism. We aimed to elucidate whether lipid levels are associated with bone mineral density (BMD) in a cohort of postmenopausal women., Design: A cross-sectional study of participants in the Chronic Ailment Reduction after MENopause (CARMEN) cohort. Women underwent assessment of clinical and analytical parameters, including fasting lipid levels. BMD was assessed at both lumbar spine and hip. Homogeneity in the cohort was optimized by filtering out a series of confounding variables with a known impact on bone., Main Outcome Measures: Association of BMD at lumbar spine and femoral neck with lipid levels., Results: A total of 667 of the 1304 screened women were analyzed. A strong correlation was revealed between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in univariate analysis. Multivariate analysis detected a significant positive association of HDL-C with BMD at both spine (p = 0.007) and femoral neck (p = 0.013). Other independent predictors of spine BMD were years since menopause (ysm, negatively associated), and body mass index (BMI) and estradiol, both positively associated with BMD. The other independent variables in the femoral neck were ysm and glucose (negatively associated) and BMI, estradiol, and phosphate, all positively associated with BMD., Conclusion: Levels of HDL-C, but not TC, LDL-C or triglycerides, were positively associated with BMD at both the lumbar spine and femoral neck in a homogeneous cohort of postmenopausal women., (Copyright © 2021 Elsevier B.V. All rights reserved.)

ABSTRACT Objective To describe the effect of the intermittent administration of vaginal progesterone and a low-dose estradiol patch on endometrial stability, as assessed by the rate of amenorrhea and endometrial stimulation. Methods This was an open study in which 64 moderately symptomatic, postmenopausal women were treated in the outpatient clinic of our University Hospital for different intervals up to 1 year. The treatment consisted of a combination of patches delivering 25 µg/day estradiol and intravaginal pills containing 100 mg of micronized progesterone. Patches and pills were administered concomitantly in a twice-a-week protocol. The endometrial response was assessed by endovaginal ultrasound completed with suction biopsy when required. Results Both cumulative amenorrhea and no-bleeding rates increased progressively and reached 88.9% and 100.0%, respectively, by the 12th month. Isolated or repetitive episodes of bleeding, bleeding and spotting, or only spotting were reported by three, four, and 12 women, respectively. Endometrial thickness remained unaltered. Endometrium was atrophic in the seven women in whom a biopsy was performed. Conclusion The substantially reduced progestogen load determined by this combination achieved an acceptable incidence of spotting or bleeding when associated with a low estrogenic dose. There was no apparent endometrial stimulation. Additional studies are required to confirm this observation.

The specific profile of estrogens on cardiovascular risk, with limiting action on atherogenesis but a less clear protection on cardiovascular episodes, might be improved by other agonists of the estrogen receptor, such as isoflavones. By using a systematic search based on the electronic Medline database plus a hand-search of reference lists of selected review papers, we reviewed the rapidly growing body of experimental and clinical data that, on average, follow a pattern of benefit rather similar to estrogens. Experimental models have used endothelial and vascular smooth muscle cells, isolated arteries, and live animals, including monkeys. The clinical evidence arises from studies on the lipid profile and lipid oxidation, insulin resistance, hemostasis, changes in the inflammatory factors, and indicators of endothelial function, including metabolites of nitric oxide and prostacyclin. There are not randomized trials investigating the action of isoflavones on the incidence of clinical episodes, but a few recent, well-designed studies have suggested the association of the ingestion of isoflavones with a reduction in the atherosclerotic burden, as indicated by the measurement of the intima-media thickness in carotid vessels., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: F2alpha-isoprostanes are considered the most reliable index of in vivo oxidative stress. Given the implication of oxidative stress in the pathogenesis of atherosclerosis, we investigated the effects of hormone therapy on the plasma levels of F2alpha-isoprostanes., Design: Sixty-one healthy postmenopausal women were treated in a randomized trial with estradiol either orally (2 mg/day, 28 women) or transdermally (50 mug/day, 33 women) for 4 weeks. Then women in each group were randomly assigned to oral progestogen, either micronized progesterone (300 mg/day) or medroxyprogesterone acetate (5 mg/day) for 2 additional weeks. Plasma samples were collected before and at the end of each treatment period, either estradiol alone or estradiol plus progestogen. F2alpha-isoprostanes were measured by a commercial enzyme immunoassay., Results: A significant reduction in the levels of F2alpha-isoprostanes was detected only in women receiving transdermal estradiol, alone or in combination with medroxyprogesterone acetate., Conclusions: Transdermal estradiol alone or associated with medroxyprogesterone acetate decreased plasma levels of F2alpha-isoprostanes. These data elucidate additional details of the beneficial effect of estradiol on oxidative stress, a relevant mechanism in atherogenesis.

Objectives: To investigate the effects of a low transdermal estradiol dose on bone metabolism and to compare it with both the standard dose and absence of treatment., Methods: In this study performed in a third-level academic center, 66 healthy postmenopausal women underwent hormone therapy (HT) with patches containing estradiol at standard (0.050 mg/day, HT50, 33 women) or low dosage (0.025 mg/day, HT25, 33 women) and 70 women were without treatment (NT). The values (mean of three samples) of several bone biochemical parameters were compared between groups after adjusting for confounding factors. Bone mineral density (BMD) was assessed (by dual-energy X-ray absorptiometry) in the spine and hip in all cases, and a second densitometry scan was performed in 44 women., Results: Bone turnover markers tended to show lower values in the treated groups, but significance was restricted to total alkaline phosphatase (NT vs. HT25, p < 0.05) and cross-linked N-telopeptides of type I collagen (NTX) (NT vs. HT25, p < 10(-6); NT vs. HT50, p < 10(-5)). The loss of BMD observed in NT women, as assessed by the annual percentage change, was blocked in both the HT25 and HT50 women. No significant differences were detected between both HT groups., Conclusions: Low and standard dosages of transdermal estradiol were equally effective in controlling bone metabolism, as assessed by turnover markers. Additionally, NTX was confirmed as the most sensitive marker for detecting changes in bone resorption.

Background: Both the estrogen receptor (ER) alpha and beta isoforms are expressed in the endothelium. The ER beta has been assigned a crucial role in normal vascular wall function. Prostacyclin has been ascribed a beneficial effect on vessel wall physiology. Isoflavones bind with higher affinity to ER beta. We investigated the hypothesis that their administration to postmenopausal women can promote endothelial prostacyclin production., Methods: Twenty-five healthy postmenopausal women with mild climacteric symptoms received capsules containing 55 mg/day isoflavones derived from soy and red clover for 6 months. Cultured human umbilical vein endothelial cells (HUVECs) were exposed for 24 h to serum collected before the initiation of therapy and then after 3 and 6 months of continuous therapy. Prostaglandin production was measured in culture medium., Results: In the presence of serum obtained after isoflavone treatment, the prostacyclin production increased significantly from 2.7 +/- 0.5 ng/mg protein at baseline to 3.4 +/- 0.7 ng/mg protein at 3 months (p < or = 0.05), and to 3.8 +/- 0.7 ng/mg protein at 6 months (p < or = 0.05 vs. baseline and 3 months' treatment)., Conclusions: Serum obtained from postmenopausal women treated with isoflavones stimulates the capacity to produce prostacyclin by HUVECs in culture, an effect that could contribute to a beneficial cardiovascular effect of phytoestrogens.

Objective: To determine the effects of menopause and three different formulations of E2 plus medroxyprogesterone acetate on serum concentrations of basal and growth hormone-releasing hormone (GHRH)-stimulated growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, insulin, and C peptide., Design: Prospective, controlled trial., Setting: Menopausal outpatient clinic at an academic tertiary care hospital., Patient(s): Nineteen postmenopausal women with different menopausal ages. Seventeen premenopausal women were included as controls., Intervention(s): Oral estrogen (E2 valerate, 2 mg/d) or transdermal estrogen (50-microg or 100-microg E2 patch) was administered for 8 weeks. Medroxyprogesterone acetate (5 mg/d) was administered during weeks 3, 4, 7, and 8 of each protocol. Blood samples were collected before treatment and after the completion of each protocol from postmenopausal women, and on cycle days 6-8 from premenopausal women., Main Outcome Measure(s): Levels of GH, IGF-1, IGFBP-1, IGFBP-3, insulin, and C peptide., Result(s): Basal GH levels were negatively correlated with age in premenopausal women but not in postmenopausal women. The area under the GHRH-induced GH curve decreased in older postmenopausal women after the oral estrogen protocol. Levels of IGF-1 diminished after the oral E2 protocol in postmenopausal women., Conclusion(s): The administration of oral, but not transdermal, E2 plus medroxyprogesterone acetate at the usual clinical doses used in postmenopausal women decreased IGF-1 levels and the response of GH to GHRH in older women. No substantial changes were detected in IGFBP-1, IGFBP-3, insulin, or C peptide levels.