Tissue Of Postmenopausal Women Research Articles

Association of serum sclerostin levels with marrow adiposity in postmenopausal women with glucocorticoid-induced osteoporosis

BackgroundGlucocorticoids and sclerostin act as inhibitors of the Wnt signaling pathway, thereby hindering bone formation. Given the pathway's intricate association with mesenchymal stem cells, the hypothesis suggests that heightened sclerostin levels may be intricately linked to an augmentation in marrow adiposity induced by glucocorticoids. This study endeavored to delve into the nuanced relationship between circulating sclerostin and bone marrow adipose tissue in postmenopausal women grappling with glucocorticoid-induced osteoporosis (GIO).MethodsIn this cross-sectional study, 103 patients with autoimmune-associated diseases underwent glucocorticoid treatment, boasting an average age of 61.3 years (standard deviation 7.1 years). The investigation encompassed a thorough assessment, incorporating medical history, anthropometric data, biochemical analysis, and dual-energy X-ray absorptiometry measurements of lumbar and femoral bone mineral density (BMD). Osteoporosis criteria were established at a T-score of -2.5 or lower. Additionally, MR spectroscopy quantified the vertebral marrow fat fraction.ResultsBMD at the femoral neck, total hip, and lumbar spine showcased an inverse correlation with marrow fat fraction (r = –0.511 to – 0.647, P < 0.001). Serum sclerostin levels exhibited a positive correlation with BMD at various skeletal sites (r = 0.476 to 0.589, P < 0.001). A noteworthy correlation emerged between circulating sclerostin and marrow fat fraction at the lumbar spine (r = –0.731, 95% CI, –0.810 to –0.627, P < 0.001). Multivariate analysis brought to light that vertebral marrow fat fraction significantly contributed to sclerostin serum concentrations (standardized regression coefficient ß = 0.462, P < 0.001). Even after adjusting for age, body mass index, physical activity, renal function, BMD, and the duration and doses of glucocorticoid treatment, serum sclerostin levels maintained a significant correlation with marrow fat fraction.ConclusionsCirculating sclerostin levels exhibited a noteworthy association with marrow adiposity in postmenopausal women grappling with GIO.

FRI407 Identification Of AIPB Expression For Early Breast Cancer Prediction

Abstract Disclosure: N.E. Doetch: None. H.S. Bose: None. The incidence of developing invasive breast cancer in women is about 14% during their lifetime and accounts for over 16% of all female cancers. Breast cancer is categorized based on the presence and absence of receptors including Estrogen Receptor (ER+/-), Progesterone Receptor (PR+/-), and Human Epidermal Growth Factor 2 Receptor (HER2+/-). Patients with Estrogen Receptor (ER+) and Progesterone Receptor (PR+) can participate in treatment catered to targeting both hormonally regulated receptors. Estradiol or estrogen are required and promote the growth of 80% of hormone receptor positive breast cancers which is regulated by Aromatase, a rate-limiting enzyme catalyzing the conversion of testosterone to estradiol. By decreasing estradiol synthesis, reduction in the progression of ER+/PR+ breast cancer is attainable.The expression of aromatase is increased in the ovaries of pre-menopausal women with substantial increase in peripheral and breast tissue in post-menopausal women contributing to tumor growth. “Aromatase Interacting Partner in Breast” (AIPB) has an inhibitory effect on aromatase causing a reduction in estradiol synthesis. AIPB is stimulated by detectable estrogen levels but remains unaffected by cAMP and inactivated cycloheximide. Expressed levels of AIPB were similar in unaffected breast tissue and WT MCF-12A breast cells. Western blot with tumorigenic human breast tissues showed decreased AIPB expression in ER+/PR+/HER2- tumors. We created conditional overexpression of AIPB under Tetracycline control that synthesized 3.52 pg/mL of estradiol. This was a 3-fold reduction in comparison to unaffected breast tissue and WT MCF-12A suggesting a leaky expression in tumorigenic breast cells. Findings led to hypothesis that AIPB stabilization is essential in promoting AIPB-Aromatase interaction resulting in decreased estradiol synthesis. The standard treatment for ER+/PR+ tumors, Tamoxifen, was incubated with MCF-12A cells overexpressing AIPB at varying Tamoxifen concentrations for different timed intervals and compared to untreated MCF-12A cells overexpressing AIPB and WT MCF-12A cells. Results yielded that AIPB expression in cells treated with Tamoxifen were substantially increased and no significant AIPB expression in untreated cells. MCF-12A-AIPB cells underwent incubation with Tamoxifen for 24h, soluble complex isolation, and a density gradient centrifugation. Western blotting with the CT antibody yielded one region in the density gradient fractionation in treated cells as compared to no complex formation in untreated cells. Therefore, AIPB confirmed crucial role in the pathophysiology of breast tumor development and maintenance of proper estradiol levels during post-menopause and tumorigenesis. The findings emphasize ability for future advancements in the early prediction of breast cancer with the identification of AIPB expression. Presentation: Friday, June 16, 2023

Histoarchitectonics of paraurethral tissue in women with stress urinary incontinence

Aim: to reveal morphological features of paraurethral tissue in postmenopausal women with stress urinary incontinence (SUI).Materials and Methods. A prospective cross-sectional trial was conducted, which included 30 women with SUI combined with POP-Q (Pelvic Organ Prolapse Quantification) stage I–II cystocele, aged 55 to 75 years. All patients underwent surgical treatment such as anterior colporrhaphy, cystocele plasty with own tissues, urethropexy with synthetic loop followed by morphological study of histological samples.Results. Profound alterations in architectonics of the connective tissue were revealed. Structural changes occurring in the paraurethral tissue are characterized by fragmentation of collagen and elastin fibers as well as their critically lowered thickness and volume, and destruction of strong inter-fiber bonds. This indicates about disintegration of the collagen-elastin skeleton being a part of the ligamentous apparatus involved in urinary retention.Conclusion. The study of the morphological aspects related to stress incontinence including use of immunohistochemical research methods will provide deeper insights into pathogenetic mechanisms behind such pathological condition. Thus, it will be possible to implement a personalized approach to the tactics of management and the choice of therapeutic method for patients with SUI aimed to increase in its effectiveness.

Longitudinal patterns of abdominal visceral and subcutaneous adipose tissue, total body composition, and anthropometric measures in postmenopausal women: Results from the Women's Health Initiative.

Abdominal adiposity, including visceral and subcutaneous abdominal adipose tissue (VAT and SAT), is recognized as a strong risk factor for cardiometabolic disease, cancer, and mortality. The primary aim of this analysis is to describe longitudinal patterns of change in abdominal adipose tissue in postmenopausal women, overall and stratified by age, race/ethnicity, and years since menopause. The data are from six years of follow up on 10,184 postmenopausal women (7828 non-Hispanic White women, 1423 non-Hispanic Black women, and 703 Hispanic women) who participated in the Women's Health Initiative (WHI). The WHI is a large prospective cohort study of postmenopausal women across the United States. All participants in this analysis had DXA scans in the 1990s as part of the WHI protocol. Hologic APEX software was used to re-analyze archived DXA scans and obtain measures of abdominal adipose tissue. Analyses examined differences in abdominal adipose tissue, overall adiposity, and anthropometric variables. There were important differences in VAT and SAT by age and race/ethnicity. In women <60 years, VAT increased over the follow-up period, while in women ≥70 years, VAT decreased. Non-Hispanic Black women had the highest levels of SAT. Hispanic women had the highest VAT levels. Women more than ten years since menopause had less SAT and more VAT than women less than ten years since menopause, resulting in a higher VAT/SAT ratio. There was a moderate to strong correlation between measures of abdominal adipose tissue and anthropometric measurements of body size. Still, there were substantial differences in the quantity of VAT and SAT within BMI and waist circumference categories. These results demonstrate differences in VAT and SAT according to age, race/ethnicity, time since menopause, and compared to standard measures of body composition in a large and diverse cohort of postmenopausal women.

Endometrial microbiota from endometrial cancer and paired pericancer tissues in postmenopausal women: differences and clinical relevance.

ObjectiveThe incidence of postmenopausal endometrial cancer (EC) is rising, and the uterine microbiota has recently been suggested to be an etiology of EC. However, the differences in microbiota profiles in paired EC and the adjacent non-EC endometrium, and the functional microbiota of clinical relevance remain largely unknown. Therefore, we examined the differences in microbiota profiles between EC and non-EC endometrium and investigated their clinical relevance to EC.MethodsTwenty-eight EC-affected postmenopausal women undergoing hysterectomy were enrolled. Endometrial microbiome from paired EC and adjacent non-EC tissue samples were detected using 16S rRNA sequencing, and the data were analyzed using R language software.ResultsThe α diversity and evenness of the endometrial bacterial community significantly increased in EC tissues than those in pericancer tissues (P < 0.05 for all variables). Lactobacillus and Gardnerella were the main bacterial genera present in both EC and adjacent non–EC-invading endometrium, whereas Prevotella, Atopobium, Anaerococcus, Dialister, Porphyromonas, and Peptoniphilus were more commonly enriched in the EC endometrium (corrected P < 0.05 for all variables). Finally, the abundance of some observed endometrial bacteria was associated with clinical aspects, particularly the vaginal pH, vaginal Lactobacillus abundance, and EC clinical stage.ConclusionsPaired EC and adjacent non-EC endometrium harbor different endometrial microbiota, and the functional bacteria residing in the endometrium are clinically relevant but require further investigation.

Distinct inflammatory signatures of upper- and lower-body adipose tissue in postmenopausal women with normal weight and obesity

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Glycine Max (L.) Merr isoflavone gel improves vaginal vascularization in postmenopausal women

Objective: This study aimed to analyze the effects of isoflavones from Glycine max (L.) Merr (soy) used topically as a vaginal gel on the induction of vascularization of the vaginal tissue in postmenopausal women.Study design: A placebo-controlled, randomized, double-blind trial was conducted with 22 postmenopausal women, randomly allocated for treatment with Glycine max (L.) Merr isoflavone 4% vaginal gel daily for 12 weeks or with placebo gel for the same period.Main outcome measure: Vaginal microbiopsies were collected before and after the 12-week treatment. Immunohistochemistry analyses were performed to provide a blood vessel count per field in the vaginal tissue, pre and post intervention.Results: The isoflavone group exhibited a significant increase in blood vessels per field relative to baseline, whereas the placebo group showed no difference compared to baseline. There was a significant difference in the increase of the number of blood vessels between the isoflavone and placebo groups.Conclusion: The results showed that local administration of Glycine max (L.) Merr isoflavone gel promoted a significant improvement in the number of blood vessels in the vaginal tissue of postmenopausal women.

Abstract OT3-09-02: A large-scale multicenter phase II study evaluating the protective effect of a tissue selective estrogen complex (TSEC) in women with newly diagnosed ductal carcinoma in situ (DCIS)

Abstract Background: TSECs were developed to treat menopausal symptoms after progesterone containing hormone replacement therapy was found to significantly increase the risk of invasive breast cancer (IBC). The first of this class of agents combines conjugated estrogens (CE), a collection of steroidal estrogens that collectively have both estrogen receptor (ERα) agonistic and antagonistic activity, and bazedoxifene (BZA), a third generation selective estrogen receptor modulator that does not stimulate the mammary gland or endometrium. The FDA approved CE/BZA for treatment of menopausal symptoms and osteoporosis after five randomized placebo controlled trials demonstrated the safety, efficacy and tolerability of CE/BZA in healthy postmenopausal women. Since then, a substantial body of evidence has emerged suggesting that CE/BZA may have additional therapeutic benefits in women. It is widely accepted that progression to IBC occurs through both epithelial and stromal mechanisms. Recent in vitro and in vivo data provide support that CE/BZA prevents progression to IBC through its effects on both epithelium and stroma. In epithelial cells, CE/BZA antagonizes estrogen-induced proliferation and expression of markers of ERα activity and also degrades ERα protein. In the stroma, CE/BZA increases expression of the scavenger receptor CD36 and consequently, reduces expression of extracellular matrix proteins (ECM) and pro-inflammatory cytokines that have been shown to contribute to the development of pro-tumorigenic microenvironment. Based on these preliminary data, we hypothesized that CE/BZA will have an anti-tumorigenic effect in the breast. Our ultimate objective is to provide postmenopausal women diagnosed with DCIS a novel and safe therapeutic option to prevent progression to IBC. Specific Aims: Aim 1: To assess epithelial contributions by determining if a short intervention of CE/BZA will have antagonistic activity in breast epithelium of postmenopausal women with ER + DCIS. Aim 2: To assess stromal contributions by determining if a short intervention of CE/BZA will alter expression of stromal markers of progression in breast tissue of postmenopausal women with ER + DCIS. Aim 3: To determine if a short intervention of CE/BZA is well tolerated and safe in postmenopausal women with ER + DCIS. Trial Design: We are currently conducting a multicenter randomized placebo controlled window of opportunity trial with CE/BZA in post-menopausal women with DCIS, a non-obligate precursor to IBC. The duration of intervention is 28 ± 7 days prior to surgical resection to enable comparison of CE/BZA on the breast using the diagnostic core biopsy and surgical sample. To date 33/166 women have enrolled in the trial. Eligibility Criteria: Post-menopausal women between 18-79 years of age diagnosed with ER (+) DCIS (&amp;gt;1cm on imaging) undergoing surgery are eligible. Women must not be on current hormonal therapy, have a current or past diagnosis of IBC, other ER sensitive tumors or have recurrent DCIS. Statistics: Results will be compared between diagnostic biopsy and surgical resection specimens and contrasted between the CE/BZA intervention group and placebo group using Fisher’s exact test for categorical variables and independent sample t-tests, or rank sum tests for continuous data. For RNAseq data, transcripts that have &amp;gt;1.5-fold expression change (at 20% FDR) between control and experimental samples will be used for downstream analysis, such as to plot heat maps, pathway and gene ontology analysis. Summary: At the conclusion of this study, we will have the first direct evidence of the potential benefits of CE/BZA therapy on DCIS lesions in the human breast, along with an initial assessment of symptoms and pharmacogenomics that will inform the design of future studies. Citation Format: Swati A. Kulkarni, Geoffrey Greene, Thea Tlsty, Luis Blanco, Judy Garber, Al George, Fred Rademaker, Seema A Khan, Nora Hansen, Kevin Bethke, Rebecca Aft, Julia Tchou. A large-scale multicenter phase II study evaluating the protective effect of a tissue selective estrogen complex (TSEC) in women with newly diagnosed ductal carcinoma in situ (DCIS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-09-02.

LncRNA and mRNA Expression Profiling in the Periurethral Vaginal Wall Tissues of Postmenopausal Women with Stress Urinary Incontinence.

Stress urinary incontinence (SUI) is one of the major pelvic floor disorders affecting postmenopausal women. To investigate the lncRNA and mRNA expression profiling of SUI in postmenopausal women, we used a microarray analysis to examine the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the periurethral vaginal wall of postmenopausal women with SUI. A total of 8840 lncRNAs and 7102 mRNAs were dysregulated in the two groups (absolute fold change ≥ 2 and P <0.05). The expression levels of five randomly selected lncRNAs and mRNAs were validated by quantitative real-time PCR. A functional analysis revealed that several lncRNAs are involved in the lysosome pathway associated with extracellular matrix (ECM) remodeling. In addition, we also found several mRNAs involved in fibroblast pseudopodia formation, fibroblast growth, and the regulation of smooth muscle cell differentiation in the urinary tract. Our study offers essential data regarding differentially expressed lncRNAs and mRNAs and may provide new potential candidates for the study of SUI.

Condition of bone tissue in postmenopausal women with type 2 diabetes mellitus of Buryat population

BACKGROUND: In most countries, there is a rapid increase in the population of patients with type 2 Diabetes Mellitus (DM). Bone changes in postmenopausal women with type 2 DM are associated with increased bone mineral density (BMD). The study of metabolic processes in bone tissue in comorbid pathology in different ethnic groups is continuing.&#x0D; AIMS: To study the concentration of markers of bone remodeling and indicators of BMD in postmenopausal women with type 2 DM of the Buryat population.&#x0D; MATERIALS AND METHODS: Thirty-nine postmenopausal women with type 2 DM (22 Russian population and 17 Buryat population) were examined. The comparison group consisted of 42 postmenopausal women (21 Russian population and 21 - Buryat population). The study of BMD in the lumbar spine (L1-L4), the femoral neck (Neck), and the proximal femur (Total hip) was performed using dual-energy X-ray absorptiometry. Parameters of osteocalcin (OC), type 1 N-terminal procollagen propeptide (P1NP), C-terminal telopeptides of type I collagen (-Cross laps), 25(OH) vitamin D and ionized calcium were evaluated.&#x0D; RESULTS: The presented study revealed a simultaneous increase in osteosynthesis: ОС (p=0.048) and P1NP (p=0.016) and in the bone resorption marker -Cross laps (p=0.020) accompanied by the absence of changes in BMD in women with type 2 DM in the postmenopausal period of the Buryat population relative to women with type 2 DM in the postmenopausal state of the Russian population. A decrease in osteosynthesis parameters (ОC, p=0.021; P1NP, p=0.029) with an increase in BMD L1-L4 (p=0.024) and BMD Total hip (p=0.039) in postmenopausal women with type 2 DM of the Buryat population was found relative to the women of the Buryat population in comparison group.&#x0D; CONCLUSIONS: The state of bone tissue in postmenopausal women with type 2 DM of the Buryat population is characterized by the activation of bone remodeling processes.

Increased expression of aromatase cytochrome P450 enzyme is associated with prolactinoma invasiveness in post-menopausal women.

ObjectivesTo investigate the expression levels of aromatase cytochrome P450 enzyme (P450AROM) and related molecules—estrogen receptor-beta (ER-β), Ki-67, and p53—in prolactinoma tumor tissue from pre- and post-menopausal women, and to determine the associations of tumor invasiveness with expression levels of these genes.MethodsThis study recruited 90 patients with prolactinoma who underwent adenoidectomy between 2012 and 2017. Information was collected regarding clinical characteristics, hormones, laboratory tests, and magnetic resonance imaging-assessed tumor invasiveness. Expression levels of P450AROM, ER-β, Ki-67, and p53 were examined by immunohistochemistry in prolactinoma tissues.ResultsIncreased P450AROM expression was found in invasive prolactinoma tissues in post-menopausal women, compared with its expression in non-invasive prolactinoma tissues. ER-β level was significantly higher in patients resistant to treatment with bromocriptine, a dopamine agonist. However, there were no differences in rate of resistance to treatment (8.2% vs. 3.4%) or expression levels of P450AROM, Ki-67, p53, and ER-β between pre- and post-menopausal patients.ConclusionsOur results demonstrated that increased P450AROM expression in prolactinoma of post-menopausal women was positively associated with invasiveness. Moreover, ER-β level was higher in both pre- and post-menopausal patients who were resistant to dopamine agonist treatment.

SAT-343 Immunohistochemical Expression of Luteinizing Hormone/Human Chorionic Gonadotropin Receptor (LH/hCG Receptor) in Adrenal Adenomas of Postmenopausal Women

Background: Increasingly, patients are found to have incidentally found adrenal adenomas on imaging performed for other purposes. Further biochemical work-up results in a diagnosis of mild hypercortisolism in as many as 30% of these patients. The incidence of adrenal adenomas and Cushing’s is higher in women than men with peak incidence ages 50-70. Elevated expression of gonadal markers such as LH/hCG receptor and the gonadal transcription factor GATA-4 has been well described in post-gonadectomy induced adrenal cortical neoplasia in neutered ferrets and certain mouse strains. The majority of these neoplasms of the adrenal cortex, which share a common embryologic progenitor with the gonads in the urogenital ridge, produce sex steroids and appear to differentiate towards a “gonadal” molecular profile. Isolated case reports have demonstrated LH/hCG receptor expression in adrenal secretory tumors in postmenopausal women and pregnant females. Taken together, there is strong evidence that a subset of adrenal tumors is driven by LH in postmenopausal women. Hypothesis: We hypothesized that adrenal adenomas producing secretory syndromes in postmenopausal women express LH/hCG receptor. Methods: 24 archival adrenal tissues from women >50 years of age with hypersecretory syndromes (primary aldosteronism and Cushing’s) were obtained with IRB approval. The samples were immunostained for expression of the LH/hCG receptor (monoclonal unconjugated LHR Antibody (LHCGR/1417), Novus Biologicals, CO) utilizing the Streptavidin–Biotin staining method. The slides were reviewed in a blinded fashion, and cytoplasmic, membrane, and nuclear expression of the markers were graded as no immunoreactivity, or 1+, 2+, or 3+ staining. Results: All 24 adenomas had demonstrated expression of LH/hCG receptor in both normal and adenomatous tissue. The staining in adenomas was heterogeneous, with clusters of densely stained LH/hCG receptor positive cells found selectively in areas of the adenomas. In addition, these clusters were found in normal adjacent adrenal tissue primarily in the subcapsular, zona glomerulosa region, an area where the putative adrenal cortical stem cells are found. Conclusion: LH/hCG receptor was found to be expressed in normal adrenocortical and adenomatous tissue in postmenopausal women, a population that has elevated serum LH levels. These findings may have clinical implications and provide a rationale for the treatment of secretory adrenal adenomas with GnRH agonists or antagonists in postmenopausal women.

OBESITY AND OSTEOPOROSIS-CONNECTIONS BETWEEN ADIPOSE TISSUE AND BONE.

The adipose and osseous tissue, although both derived from the connective tissues, perform different functions. In the common opinion, obesity might be a protective factor against bone loss and osteoporosis. The adipose tissue is a recognized major endocrine organ, producing a number of active biological substances, which affect the bone mass. Adipocyte and osteoblast are derived from the same mesenchymal stem cells. Therefore abnormal secretion of adipocytokines may play an important role not only in pathogenesis of the obesity, but also can influence the bone . It is supposed that obesity might have a protective effect on bone tissue in postmenopausal women, by increasing the load on the axial skeleton and because of its hormonal activity.

Exosomes secreted by adipose-derived mesenchymal stem cells regulate type I collagen metabolism in fibroblasts from women with stress urinary incontinence

BackgroundMesenchymal stem cells (MSC) have gained credibility as a therapeutic tool partly due to their potential to secrete factors such as cytokines and chemokines. Recently, exosomes, which mediate intercellular communication by delivering biomolecules such as mRNA and miRNA into recipient cells, have gained attention as a new and valuable therapeutic strategy in regenerative medicine. However, the potential role of exosomes secreted by adipose-derived mesenchymal stem cells (adMSC-Exos) in collagen metabolism is not well understood. The purpose of this study was to evaluate the effects of adMSC-Exos on collagen metabolism in cultured fibroblasts from women with stress urinary incontinence (SUI).MethodsPeriurethral vaginal wall tissues of postmenopausal women with or without SUI were collected during transvaginal surgical procedures. Primary fibroblasts were cultured from periurethral vaginal wall tissues, and the levels of type I collagen mRNA and protein were examined by qRT-PCR and western blotting. MSC were isolated from human adipose tissue by enzymatic digestion. Exosomes were prepared by ultracentrifugation of adMSC-conditioned medium (adMSC-CM) and were confirmed by transmission electron microscopy and western blot analyses. The effects of adMSC-CM and adMSC-Exos were assessed using qRT-PCR and western blotting.ResultsThe type I collagen content was significantly decreased in periurethral vaginal wall tissues and cultured vaginal fibroblasts from women with SUI. adMSC-CM increased the expression of the col1a1 gene in vaginal fibroblasts from women with SUI. adMSC-Exos could be successfully isolated from adMSC-CM and could be transferred to fibroblasts efficiently. adMSC-Exos increased the expression of col1a1 in vaginal fibroblasts from women with SUI, and when the fibroblasts were treated with adMSC-Exos, the expression levels of TIMP-1 and TIMP-3 in fibroblasts were upregulated, with significant downregulation of MMP-1 and MMP-2 expression levels.ConclusionsadMSC-Exos increased type I collagen contents by increasing collagen synthesis and decreasing collagen degradation in vaginal fibroblasts from women with SUI. adMSC-Exos may be a novel therapeutic approach for treating SUI.

Less Waste on Waist Measurements: Determination of Optimal Waist Circumference Measurement Site to Predict Visceral Adipose Tissue in Postmenopausal Women with Obesity.

With obesity being a leading cause of preventable death, it is vital to understand how best to identify individuals with greater risk of metabolic disease, especially those with high visceral adipose tissue (VAT). This study aimed to determine whether three commonly used waist circumference (WC) measurement sites could provide accurate estimations of VAT, as determined by magnetic resonance imaging (MRI), which is a gold standard for measuring VAT, in postmenopausal women with obesity. VAT volume was measured by MRI of the total abdomen in 97 women aged 57.7 ± 0.4 years (mean ± SEM), mean body mass index 34.5 ± 0.2 kg/m2. WC was measured at the midpoint between the lowest rib and the iliac crest (WCmid), the narrowest point of the torso (WCnarrow), and at the level of the umbilicus (WCumbilicus). WC differed significantly according to measurement site, with WCnarrow (102.1 ± 0.7 cm) < WCmid (108.3 ± 0.7 cm) < WCumbilicus (115.7 ± 0.8 cm) (p < 0.001). WCmid, WCnarrow and WCumbilicus were all significantly correlated with VAT, as measured by MRI (r = 0.581, 0.563 and 0.390, respectively; p < 0.001 for all), but the relationships between WCmid or WCnarrow and VAT determined by MRI were stronger than for WCumbilicus. Measurement of either WCmid or WCnarrow provides valid estimates of VAT in postmenopausal women with obesity, with WCnarrow being favoured in light of its greater ease and speed of measurement in this population.

Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet

PurposeWe studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue.MethodsFifty-eight postmenopausal women with overweight (BMI 32.5 ± 5.5) were randomized to eat an ad libitum Paleolithic-type diet (PD) aiming for a high intake of protein and unsaturated fatty acids or a prudent control diet (CD) for 24 months. Anthropometry, plasma adipokines, gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue (SAT) and lipoprotein lipase (LPL) activity and mass in SAT were measured at baseline and after 6 months. LPL mass and activity were also measured after 24 months.ResultsThe PD led to improved insulin sensitivity (P < 0.01) and decreased circulating triglycerides (P < 0.001), lipogenesis-related factors, including LPL mRNA (P < 0.05), mass (P < 0.01), and activity (P < 0.001); as well as gene expressions of CD36 (P < 0.05), fatty acid synthase, FAS (P < 0.001) and diglyceride acyltransferase 2, DGAT2 (P < 0.001). The LPL activity (P < 0.05) and gene expression of DGAT2 (P < 0.05) and FAS (P < 0.05) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity (P < 0.05) remained significantly lowered in the PD group compared to the CD group at 24 months.ConclusionsCompared to the CD, the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight. This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity.

Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women.

In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.

Quantification of Estrogen Receptor Expression in Normal Breast Tissue in Postmenopausal Women With Breast Cancer and Association With Tumor Subtypes.

Estrogen exposure is important in the pathogenesis of breast cancer and is a contributing risk factor. In this study we quantified estrogen receptor (ER) alpha expression in normal breast epithelium (NBR) in women with breast cancer and correlated it with breast cancer subtypes. Tissue microarrays were constructed from 204 breast cancer patients for whom normal breast tissue away from tumor was available. Slides stained with ER were scanned and expression in normal terminal duct lobular epithelium was quantitated using computer-assisted image analysis. ER expression in normal terminal duct lobular epithelium of postmenopausal women with breast cancer was significantly associated with estrogen and triple (estrogen, progesterone receptors, and HER2) negative phenotypes. Also increased age at diagnosis was significantly associated with ER expression in NBR. ER positivity in normal epithelium did not vary by tumor size, lymph node status, tumor grade, or stage. On the basis of quantitative image analysis, we confirm that ER expression in NBR increases with age in women with breast cancer, and report for the first time, a significant association between ER expression in NBR with ER-negative and triple-negative cancers in postmenopausal women.

The Relationship Between Bone Mineral Density and Adipose Tissue of Postmenopausal Women

The Relationship Between Bone Mineral Density and Adipose Tissue of Postmenopausal Women

Immunohistochemical expression of hypoxia-inducible factor-1α in stromal cells of vaginal tissue in post-menopausal women with pelvic organ prolapse.

Background & objectives:Pelvic organ prolapse (POP) is a common medical condition that affects adult women of different ages. The support of a normal pelvic floor is the result of complex interactions between ligaments, muscles, connective tissue and vaginal walls. Hypoxia and oxidative stress can reduce protein synthesis in the pelvic muscles that may contribute to muscular atrophy. Hypoxia-inducible factor-1α (HIF-1α) is a transcriptional activator which, expressed in response to hypoxia, activates a number of genes involved in cellular response to hypoxia. However, a potential role of hypoxia and oxidative stress in pathogenesis of POP is not known. This study was aimed to compare the level of HIF-1α immunohistochemical expression in the vaginal stromal cells of postmenopausal women with and without POP.Methods:Samples of the vaginal tissue from 120 menopausal women were obtained during surgery, and immunohistochemical expression of HIF-1α was assessed. There were 60 women with POP while 60 women in the control group were without prolapse but with benign gynaecological diseases.Results:In post-menopausal women with prolapse, significant differences were observed in the number of HIF-1α-positive stromal cells in the vaginal tissue compared to the control group. There was a significant increase in the number of HIF-1α in the stromal cells of the vaginal tissue in women with prolapse.Interpretation & conclusions:Difference in expression of HIF-1α in stromal cells of the vaginal tissue in the post-menopausal women with and without POP suggests that prolonged hypoxia probably has an important role in the aetiopathogenesis of POP.