ResearchPad - menopause https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Prevalence of endosalpingiosis and other benign gynecologic lesions]]> https://www.researchpad.co/article/elastic_article_14492 Endosalpingiosis, traditionally regarded as an incidental pathological finding, was recently reported to have an association with gynecologic malignancies. To determine the prevalence of endosalpingiosis, we evaluated all benign appearing adnexal lesions using the Sectioning and Extensively Examining-Fimbria (SEE-Fim) protocol, and queried the pathology database for the presence of endosalpingiosis, gynecologic malignancy, endometriosis, Walthard nests, and paratubal cysts. Using the SEE-Fim protocol, the prevalence of endosalpingiosis, endometriosis, Walthard nests, and paratubal cysts were 22%, 45%, 33%, and 42% respectively, substantially higher than previously reported. All lesions were observed to increase with age except endometriosis which increased until menopause then decreased dramatically. Among specimens including ovarian tissue, the prevalence of implantation of at least one lesion type was ubiquitous in patients age 51 and older (93%). The clinical significance of endosalpingiosis should be a continued area of research with larger trials assessing prevalence, factors affecting incidence, and association with malignancy. Our findings contribute to elucidating the origin of ectopic lesions and gynecologic disease risk.

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<![CDATA[Searching for predictors of sense of quality of health: A study using neural networks on a sample of perimenopausal women]]> https://www.researchpad.co/article/5c37b78ed5eed0c48449043d

Background

We assumed that perimenopausal women’s sense of quality of health (SQH) is a subjective evaluation of their psycho-physical health, and comprises three dimensions: sense of quality of life, menopausal symptoms, and the level of positive and negative affect.

Purpose

The aim of the study was to: 1) test a model about SQH, and 2) explore the role of personality traits, self-esteem, body self, and self-stereotype as predictors of SQH.

Methods

The sample included 201 women aged between 45 and 55 (50.11±3.07). Participants filled out the Rosenberg Self-Esteem Scale, the Personality Inventory based on the Big Five Factor Model, the Body Self Questionnaire, and a survey querying perimenopausal women’s self-stereotype. To determine the individual SQH dimensions we used the Sense of Quality of Life Questionnaire, the Menopause Symptom List, and the Positive and Negative Affect Schedule. To verify the assumptions of the SQH model and look for SQH predictors we conducted a neural networks analysis with structure optimization via genetic algorithms (a multivariate analysis).

Results

The SQH model was verified in the course of several neural networks analyses with structure optimization via genetic algorithms (R = 0.849, R2 = 0.723, F = 133,232, p < 0.01). Moreover, we confirmed that SQH comprised three dimensions: quality of life, menopausal symptoms, and affect. SQH and menopausal symptoms were correlated. Similarly, positive and negative affect modified the women’s global sense of quality of life. SQH predictors included: personality traits, self-esteem, the body-self, and menopausal woman’s self-stereotype.

Conclusion

In practical terms, our findings may help raise awareness among women and medical practitioners, calling for a holistic approach to the health of menopausal women. Our findings may also facilitate the creation of both prevention and therapeutic programs for women transitioning through menopause, for example, cognitive-behavioral therapy.

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<![CDATA[Increased Alzheimer's risk during the menopause transition: A 3-year longitudinal brain imaging study]]> https://www.researchpad.co/article/5c1ab866d5eed0c484027e49

Two thirds of all persons with late-onset Alzheimer’s disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer’s disease (AD) biomarker changes [brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife. Fifty-nine 40–60 year-old cognitively normal participants with clinical, neuropsychological, and brain imaging exams at least 2 years apart were examined. These included 41 women [15 premenopausal controls (PRE), 14 perimenopausal (PERI), and 12 postmenopausal women (MENO)] and 18 men. We used targeted minimum loss-based estimation to evaluate AD biomarker and cognitive changes. Older age was associated with baseline Aβ and neurodegeneration markers, but not with rates of change in these biomarkers. APOE4 status influenced change in Aβ load, but not neurodegenerative changes. Longitudinally, MENO and PERI groups showed declines in estrogen-dependent memory tests as compared to men (p < .04). Adjusting for age, APOE4 status, and vascular risk confounds, the MENO and PERI groups exhibited higher rates of CMRglc decline as compared to males (p ≤ .015). The MENO group exhibited the highest rate of hippocampal volume loss (p’s ≤ .001), and higher rates of Aβ deposition than males (p < .01). CMRglc decline exceeded Aβ and atrophy changes in all female groups vs. men. These findings indicate emergence and progression of a female-specific hypometabolic AD-endophenotype during the menopausal transition. These findings suggest that the optimal window of opportunity for therapeutic intervention to prevent or delay progression of AD endophenotype in women is early in the endocrine aging process.

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<![CDATA[Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies]]> https://www.researchpad.co/article/5c06f032d5eed0c484c6d377

Background

Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.

Methods and findings

A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40–44 (early), 45–49, 50–51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures.

Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73–2.44) (p < 0.001) and early menopause (1.80; 1.66–1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04–1.23; p = 0.006) and 1.15 (1.05–1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45–49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15–20 years, the risk was markedly higher for premature (15.58; 11.29–19.86; p < 0.001) and early (6.55; 5.04–8.52; p < 0.001) menopause. Also, current smokers with 11–15 pack-years had over 4-fold (4.35; 2.78–5.92; p < 0.001) and 3-fold (3.01; 2.15–4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98–1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias.

Conclusions

The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

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<![CDATA[P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdbbce

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC.

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<![CDATA[Age at Menarche and Natural Menopause and Number of Reproductive Years in Association with Mortality: Results from a Median Follow-Up of 11.2 Years among 31,955 Naturally Menopausal Chinese Women]]> https://www.researchpad.co/article/5989db44ab0ee8fa60bd7cc6

Background

Studies conducted in Western countries suggest that early age at menarche and early age at menopause are both associated with increased total mortality, but limited data are available for Asian populations. We examined associations of age at menarche and natural menopause and duration of the reproductive span with mortality in a population-based cohort study of Chinese women.

Methods

We evaluated the effects of age at menarche, age at natural menopause, and number of reproductive years on total and cause-specific mortality among 31,955 naturally menopausal Chinese women who participated in the Shanghai Women's Health Study, a population-based, prospective cohort study.

Results

A total of 3,158 deaths occurred during a median follow-up of 11.2 years. Results from Cox proportional hazards models showed that younger age at menopause (<46.64 years) was associated with higher risk of total mortality (Ptrend  = 0.02). Younger age at menarche (<14 years) was associated with higher risk of mortality from stroke (Ptrend  = 0.03) and diabetes (Ptrend = 0.02) but lower risk of mortality from respiratory system cancer (Ptrend  = 0.01). Women with a shorter reproductive span had lower risk of mortality from gynecological cancers (Ptrend = 0.03).

Conclusions

Our study found that menstrual characteristics are important predictors of mortality, suggesting an important role of sex hormones in biological aging.

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<![CDATA[Differential Effects of E2 on MAPK Activity in the Brain and Heart of Aged Female Rats]]> https://www.researchpad.co/article/5989da87ab0ee8fa60b9c8d8

Aging and the coincident loss of circulating estrogens at menopause lead to increased risks for neurological and cardiovascular pathologies. Clinical studies show that estrogen therapy (ET) can be beneficial in mitigating these negative effects, in both the brain and heart, when it is initiated shortly after the perimenopausal transition. However, this same therapy is detrimental when initiated >10 years postmenopause. Importantly, the molecular mechanisms underlying this age-related switch in ET efficacy are unknown. Estrogen receptors (ERs) mediate the neuroprotective and cardioprotective functions of estrogens by modulating gene transcription or, non-genomically, by activating second messenger signaling pathways, such as mitogen activated protein kinases (MAPK). These kinases are critical regulators of cell signaling pathways and have widespread downstream effects. Our hypothesis is that age and estrogen deprivation following menopause alters the expression and activation of the MAPK family members p38 and ERK in the brain and heart. To test this hypothesis, we used a surgically induced model of menopause in 18 month old rats through bilateral ovariectomy (OVX) followed by an acute dose of 17β-estradiol (E2) administered at varying time points post-OVX (1 week, 4 weeks, 8 weeks, or 12 weeks). Age and E2 treatment differentially regulated kinase activity in both the brain and heart, and the effects were also brain region specific. MAPK signaling plays an integral role in aging, and the aberrant regulation of those signaling pathways might be involved in age-related disorders. Clinical studies show benefits of ET during early menopause but detrimental effects later, which might be reflective of changes in kinase expression and activation status.

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<![CDATA[Dietary Deficiency of Essential Amino Acids Rapidly Induces Cessation of the Rat Estrous Cycle]]> https://www.researchpad.co/article/5989da2fab0ee8fa60b83d94

Reproductive functions are regulated by the sophisticated coordination between the neuronal and endocrine systems and are sustained by a proper nutritional environment. Female reproductive function is vulnerable to effects from dietary restrictions, suggesting a transient adaptation that prioritizes individual survival over reproduction until a possible future opportunity for satiation. This adaptation could also partially explain the existence of amenorrhea in women with anorexia nervosa. Because amino acid nutritional conditions other than caloric restriction uniquely alters amino acid metabolism and affect the hormonal levels of organisms, we hypothesized that the supply of essential amino acids in the diet plays a pivotal role in the maintenance of the female reproductive system. To test this hypothesis, we examined ovulatory cyclicity in female rats under diets that were deficient in threonine, lysine, tryptophan, methionine or valine. Ovulatory cyclicity was monitored by daily cytological evaluations of vaginal smears. After continuous feeding of the deficient diet, a persistent diestrus or anovulatory state was induced most quickly by the valine-deficient diet and most slowly by the lysine-deficient diet. A decline in the systemic insulin-like growth factor 1 level was associated with a dietary amino acid deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet with balanced amino acids maintained normal estrous cyclicity. These disturbances of the estrous cycle by amino acid deficiency were quickly reversed by the consumption of a normal diet. The continuous anovulatory state in this study is not attributable to a decrease in caloric intake but to an imbalance in the dietary amino acid composition. With a shortage of well-balanced amino acid sources, reproduction becomes risky for both the mother and the fetus. It could be viewed as an adaptation to the diet, diverting resources away from reproduction and reallocating them to survival until well-balanced amino acid sources are found.

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<![CDATA[Breast Cancer Incidence in Black and White Women Stratified by Estrogen and Progesterone Receptor Statuses]]> https://www.researchpad.co/article/5989daffab0ee8fa60bc602d

Background

There is increasing evidence that breast cancer is a heterogeneous disease presented by different phenotypes and that white women have a higher breast cancer incidence rate, whereas black women have a higher mortality rate. It is also well known that white women have lower incidence rates than black women until approximately age 40, when rate curves cross over and white women have higher rates. The goal of this study was to validate the risk of white and black women to breast cancer phenotypes, stratified by statuses of the estrogen (ER) and progesterone (PR) receptors.

Methodology/Principal Findings

SEER17 data were fractioned by receptor status into [ER+, PR+], [ER−, PR−], [ER+, PR−], and [ER−, PR+] phenotypes. It was shown that in black women compared to white women, cumulative age-specific incidence rates are: (i) smaller for the [ER+, PR+] phenotype; (ii) larger for the [ER−, PR−] and [ER−, PR+] phenotypes; and (iii) almost equal for the [ER+, PR−] phenotype. Clemmesen's Hook, an undulation unique to women's breast cancer age-specific incidence rate curves, is shown here to exist in both races only for the [ER+, PR+] phenotype. It was also shown that for all phenotypes, rate curves have additional undulations and that age-specific incidence rates are nearly proportional in all age intervals.

Conclusions/Significance

For black and white women, risk for the [ER+, PR+], [ER−, PR−] and [ER−, PR+] phenotypes are race dependent, while risk for the [ER+, PR−] phenotype is almost independent of race. The processes of carcinogenesis in aging, leading to the development of each of the considered breast cancer phenotypes, are similar in these racial groups. Undulations exhibited on the curves of age-specific incidence rates of the considered breast cancer phenotypes point to the presence of several subtypes (to be determined) of each of these phenotypes.

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<![CDATA[Signatures of reproductive events on blood counts and biomarkers of inflammation: Implications for chronic disease risk]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdbc5c

Whether inflammation mediates how reproductive events affect chronic-disease risk is unclear. We studied inflammatory biomarkers in the context of reproductive events using National Health and Nutrition Examination Survey (NHANES) data. From 15,986 eligible women from the 1999–2011 data cycles, we accessed information on reproductive events, blood counts, C-reactive protein (CRP), and total homocysteine (tHCY). We calculated blood-count ratios including: platelet-lymphocyte (PLR), lymphocyte-monocyte (LMR), platelet-monocyte (PMR), and neutrophil-monocyte (NMR). Using sampling weights per NHANES guidelines, means for counts, ratios, or biomarkers by reproductive events were compared using linear regression. We performed trend tests and calculated p-values with partial sum of squares F-tests. Higher PLR and lower LMR were associated with nulliparity. In postmenopausal women, lower PMR was associated with early age at first birth and higher NMR with later age at and shorter interval since last birth. Lower PNR and higher neutrophils and tHCY were associated with early natural menopause. In all women, the neutrophil count correlated positively with CRP; but, in premenopausal women, correlated inversely with tHCY. Reproductive events leave residual signatures on blood counts and inflammatory biomarkers that could underlie their links to chronic disease risk.

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<![CDATA[Bortezomib Prevents Acute Doxorubicin Ovarian Insult and Follicle Demise, Improving the Fertility Window and Pup Birth Weight in Mice]]> https://www.researchpad.co/article/5989dae4ab0ee8fa60bbcdb9

Increasing numbers of female patients survive cancer, but succumb to primary ovarian insufficiency after chemotherapy. We tested the hypothesis that Bortezomib (Bort) protects ovaries from doxorubicin (DXR) chemotherapy by treating female mice with Bort 1 hour prior to DXR. By preventing DXR accumulation in the ovary, Bort attenuated DXR-induced DNA damage in all ovarian cell types, subsequent γH2AFX phosphorylation, and resulting apoptosis in preantral follicles. Bort pretreatment extended the number of litters per mouse, improved litter size and increased pup weight following DXR treatment, thus increasing the duration of post-chemotherapy fertility and improving pup health. As a promising prophylactic ovoprotective agent, Bort does not interfere with cancer treatment, and is currently used as a chemotherapy adjuvant. Bort-based chemoprotection may preserve ovarian function in a non-invasive manner that avoids surgical ovarian preservation, thus diminishing the health complications of premature menopause following cancer treatment.

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<![CDATA[Urethral Dysfunction in Female Mice with Estrogen Receptor β Deficiency]]> https://www.researchpad.co/article/5989da02ab0ee8fa60b7462a

Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ERβ in stress urinary incontinence (SUI). Wild-type (ERβ+/+) and knockout (ERβ−/−) female mice were generated (aged 6–8 weeks, n = 6) and urethral function and protein expression were measured. Leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using label-free quantitative proteomics by nano-liquid chromatography–mass spectrometry (LC-MS/MS) analysis. The interaction between these proteins was further analysed using MetaCore. Lastly, Western blot was used to confirm the candidate proteins. Compared with the ERβ+/+ group, the LPP and MUCP values of the ERβ−/− group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ERβ−/− female mice; 57 proteins were up-regulated and 28 were down-regulated. The majority of the ERβ knockout-modified proteins were involved in cell-matrix adhesion, metabolism, immune response, signal transduction, nuclear receptor translational regelation, and muscle contraction and development. Western blot confirmed the up-regulation of myosin and collagen in urethra. By contrast, elastin was down-regulated in the ERβ−/− mice. This study is the first study to estimate protein expression changes in urethras from ERβ−/− female mice. These changes could be related to the molecular mechanism of ERβ in SUI.

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<![CDATA[A Systems Biology Approach Investigating the Effect of Probiotics on the Vaginal Microbiome and Host Responses in a Double Blind, Placebo-Controlled Clinical Trial of Post-Menopausal Women]]> https://www.researchpad.co/article/5989daf1ab0ee8fa60bc138d

A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each) on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains.

Trial Registration

ClinicalTrials.gov NCT02139839

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<![CDATA[Genetic Contribution of Femoral Neck Bone Geometry to the Risk of Developing Osteoporosis: A Family-Based Study]]> https://www.researchpad.co/article/5989dad7ab0ee8fa60bb871e

Femoral neck geometry parameters are believed to be as good as bone mineral density as independent factors in predicting hip fracture risk. This study was conducted to analyze the roles of genetic and environmental factors in femoral properties measured in a sample of Spanish families with osteoporotic fractures and extended genealogy. The “Genetic Analysis of Osteoporosis (GAO) Project” involved 11 extended families with a total number of 376 individuals. We studied three categorical phenotypes of particular clinical interest and we used a Hip structural analysis based on DXA to analyze 17 strength and geometrical phenotypes of the hip. All the femoral properties had highly significant heritability, ranging from 0.252 to 0.586. The most significant correlations were observed at the genetic level (ρG). Osteoporotic fracture status (Affected 2) and, particularly, low bone mass and osteoporotic condition (Affected 3) had the highest number of significant genetic correlations with diverse femoral properties. In conclusion, our findings suggest that a relatively simple and easy to use method based on DXA studies can provide useful data on properties of the Hip in clinical practice. Furthermore, our results provide a strong motivation for further studies in order to improve the understanding of the pathophysiological mechanism underlying bone architecture and the genetics of osteoporosis.

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<![CDATA[Pharmacological Inhibition of mTORC1 Prevents Over-Activation of the Primordial Follicle Pool in Response to Elevated PI3K Signaling]]> https://www.researchpad.co/article/5989dafcab0ee8fa60bc4ed9

The majority of ovarian primordial follicles must be preserved in a quiescent state to allow for the regular production of gametes over the female reproductive lifespan. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Under certain pathological conditions, the entire pool of primordial follicles matures simultaneously leading to an accelerated loss of primordial follicles and to premature ovarian failure (POF). We have previously shown that loss of Pten (phosphatase and tensin homolog deleted on chromosome ten) in mouse oocytes leads to premature activation of the entire pool of primordial follicles, subsequent follicular depletion in early adulthood, and the onset of POF. Lack of PTEN leads to increased phosphatidylinositol 3-kinase (PI3K)–Akt and mammalian target of rapamycin complex 1 (mTORC1) signaling in the oocytes. To study the functional and pathological roles of elevated mTORC1 signaling in the oocytes, we treated the Pten-mutant mice with the specific mTORC1 inhibitor rapamycin. When administered to Pten-deficient mice prior to the activation of the primordial follicles, rapamycin effectively prevented global follicular activation and preserved the ovarian reserve. These results provide a rationale for exploring the possible use of rapamycin as a drug for the preservation of the primordial follicle pool, and the possible prevention of POF.

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<![CDATA[Menopause Analytical Hormonal Correlate Outcome Study (MAHCOS) and the Association to Brain Electrophysiology (P300) in a Clinical Setting]]> https://www.researchpad.co/article/5989db00ab0ee8fa60bc672b

Various studies have demonstrated that increased leptin levels and obesity are inversely related to cognitive decline in menopausal women. It is hypothesized that adiposity is inversely correlated with cognitive decline, as women with increased weight are less vulnerable to diminishing cognition. However, it is increasingly observed that menopausal women, even with increased adiposity, experience significant cognitive decline. Positron emission tomography (PET) has been used to analyze cognitive function and processing in menopausal women. Evoked potentials (P300) and neurophysiologic tests have validated brain metabolism in cognitively impaired patients. Post-hoc analyses of 796 female patients entering PATH Medical Clinic, between January 4, 2009 and February 24, 2013, were performed as part of the “Menopause Analytical Hormonal Correlate Outcome Study” (MAHCOS). Patient age range was 39–76 years (46.7±0.2). P300 latency and amplitude correlated with a number of hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, estrone, estriol, DHEA, pregnenolone, progesterone, free and total testosterone, thyroid stimulating hormone (TSH), Vitamins D 1.25 and D 25OH, leptin, and insulin-like growth factor-binding protein 3 (IGF-BP3). Corrected statistics did not reveal significant associations with P300 latency or amplitude for these hormones except for leptin plasma levels. However, factor analysis showed that FSH and LH clustered together with Vitamin D1.25 and Vitamin D25OH, P300 latency (not amplitude), and log leptin were found to be associated in the same cluster. Utilizing regression analysis, once age adjusted, leptin was the only significant predictor for latency or speed (p = 0.03) with an effect size of 0.23. Higher plasma leptin levels were associated with abnormal P300 speed (OR = 0.98). Our findings show a significant relationship of higher plasma leptin levels, potentially due to leptin resistance, and prolonged P300 latency. This suggests leptin resistance may delay electrophysiological processing of memory and attention, which appears to be the first of such an association.

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<![CDATA[Catechol-O-Methyltransferase Gene Polymorphism Is Associated with Skeletal Muscle Properties in Older Women Alone and Together with Physical Activity]]> https://www.researchpad.co/article/5989da97ab0ee8fa60ba24b5

Background

Muscle strength declines on average by one percent annually from midlife on. In postmenopausal women this decrement coincides with a rapid decline in estrogen production. The genetics underlying the effects of estrogen on skeletal muscle remains unclear. In the present study, we examined whether polymorphisms within COMT and ESR1 are associated with muscle properties and assessed their interaction and their combined effects with physical activity.

Methodology/Principal Findings

A cross-sectional data analysis was conducted with 434 63-76-year-old women from the population-based Finnish Twin Study on Aging. Body anthropometry, muscle cross-sectional area (mCSA), isometric hand grip and knee extension strengths, and leg extension power were measured. COMT Val158Met and ESR1 PvuII genotypes were determined by the RFLP method. mCSA differed by COMT genotypes (p = 0.014) being significantly larger in LL than HL individuals in unadjusted (p = 0.001) and age- and height-adjusted model (p = 0.004). When physical activity and age were entered into GEE model, COMT genotype had a significant main effect (p = 0.038) on mCSA. Furthermore, sedentary individuals with the HH genotype had lower muscle mass, strength and power, but they also appeared to benefit the most from physical activity. No association of ESR1 PvuII polymorphism with any of the muscle outcomes was observed.

Conclusions/Significance

The present study suggests that the COMT polymorphism, affecting the activity of the enzyme, is associated with muscle mass. Furthermore, sedentary individuals with potential high enzyme activity were the weakest group, but they may potentially benefit the most from physical activity. This observation elucidates the importance of both environmental and genetic factors in muscle properties.

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<![CDATA[Predicting Total, Abdominal, Visceral and Hepatic Adiposity with Circulating Biomarkers in Caucasian and Japanese American Women]]> https://www.researchpad.co/article/5989db27ab0ee8fa60bd09c9

Background

Characterization of abdominal and intra-abdominal fat requires imaging, and thus is not feasible in large epidemiologic studies.

Objective

We investigated whether biomarkers may complement anthropometry (body mass index [BMI], waist circumference [WC], and waist-hip ratio [WHR]) in predicting the size of the body fat compartments by analyzing blood biomarkers, including adipocytokines, insulin resistance markers, sex steroid hormones, lipids, liver enzymes and gastro-neuropeptides.

Methods

Fasting levels of 58 blood markers were analyzed in 60 healthy, Caucasian or Japanese American postmenopausal women who underwent anthropometric measurements, dual energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging. Total, abdominal, visceral and hepatic adiposity were predicted based on anthropometry and the biomarkers using Random Forest models.

Results

Total body fat was well predicted by anthropometry alone (R2 = 0.85), by the 5 best predictors from the biomarker model alone (leptin, leptin-adiponectin ratio [LAR], free estradiol, plasminogen activator inhibitor-1 [PAI1], alanine transaminase [ALT]; R2 = 0.69), or by combining these 5 biomarkers with anthropometry (R2 = 0.91). Abdominal adiposity (DXA trunk-to-periphery fat ratio) was better predicted by combining the two types of predictors (R2 = 0.58) than by anthropometry alone (R2 = 0.53) or the 5 best biomarkers alone (25(OH)-vitamin D3, insulin-like growth factor binding protein-1 [IGFBP1], uric acid, soluble leptin receptor [sLEPR], Coenzyme Q10; R2 = 0.35). Similarly, visceral fat was slightly better predicted by combining the predictors (R2 = 0.68) than by anthropometry alone (R2 = 0.65) or the 5 best biomarker predictors alone (leptin, C-reactive protein [CRP], LAR, lycopene, vitamin D3; R2 = 0.58). Percent liver fat was predicted better by the 5 best biomarker predictors (insulin, sex hormone binding globulin [SHBG], LAR, alpha-tocopherol, PAI1; R2 = 0.42) or by combining the predictors (R2 = 0.44) than by anthropometry alone (R2 = 0.29).

Conclusion

The predictive ability of anthropometry for body fat distribution may be enhanced by measuring a small number of biomarkers. Studies to replicate these data in men and other ethnic groups are warranted.

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<![CDATA[Association between lifetime exposure to passive smoking and risk of breast cancer subtypes defined by hormone receptor status among non-smoking Caucasian women]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc201

Tobacco smoking is inconsistently associated with breast cancer. Although some studies suggest that breast cancer risk is related to passive smoking, little is known about the association with breast cancer by tumor hormone receptor status. We aimed to explore the association between lifetime passive smoking and risk of breast cancer subtypes defined by estrogen receptor and progesterone receptor status among non-smoking Caucasian women. A hospital-based case-control study was performed in 585 cases and 1170 controls aged 28–90 years. Information on lifetime passive smoking and other factors was collected via a self-administered questionnaire. Logistic regression was used for analyses restricted to the 449 cases and 930 controls who had never smoked actively. All statistical tests were two-sided. Adjusted odds ratio of breast cancer was 1.01 (95% confidence interval (CI): 0.72–1.41) in women who experienced exposure to passive smoking at work, 1.88 (95% CI: 1.38–2.55) in women who had exposure at home, and 2.80 (95% CI: 1.84–4.25) in women who were exposed at home and at work, all compared with never exposed regularly. Increased risk was associated with longer exposure: women exposed ≤ 20 years and > 20 years had 1.27 (95% CI: 0.97–1.66) and 2.64 (95% CI: 1.87–3.74) times higher risk of breast cancer compared with never exposed (Ptrend < 0.001). The association of passive smoking with hormone receptor-positive breast cancer did not differ from that with hormone receptor-negative breast cancer (Pheterogeneity > 0.05). There was evidence of interaction between passive smoking intensity and menopausal status in both overall group (P = 0.02) and hormone receptor-positive breast cancer group (P < 0.05). In Caucasian women, lifetime exposure to passive smoking is associated with the risk of breast cancer independent of tumor hormone receptor status with the strongest association in postmenopausal women.

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<![CDATA[Knowledge, Perceptions and Information about Hormone Therapy (HT) among Menopausal Women: A Systematic Review and Meta-Synthesis]]> https://www.researchpad.co/article/5989db3eab0ee8fa60bd5c77

Background

The use of hormone therapy (HT) by menopausal women has declined since the Women's Health Initiative randomized trial (WHI) in 2002 demonstrated important harms associated with long-term use. However, how this information has influenced women's knowledge and attitudes is uncertain. We aimed to evaluate the attitudes and perceptions towards HT use, as well as specific concerns and information sources on HT since the WHI trial.

Method/Results

We did a systematic review to assess the attitudes and knowledge towards HT in women, and estimate the magnitude of the issue by pooling across the studies. Using meta-synthesis methods, we reviewed qualitative studies and surveys and performed content analysis on the study reports. We pooled quantitative studies using a random-effects meta-analysis. We analyzed 11 qualitative studies (n = 566) and 27 quantitative studies (n = 39251). Positive views on HT included climacteric symptom control, prevention of osteoporosis and a perceived improvement in quality of life. Negative factors reported included concerns about potential harmful effects, particularly cancer risks. Sources of information included health providers, media, and social contact. By applying a meta-synthesis approach we demonstrate that these findings are broadly applicable across large groups of patients.

Conclusions

Although there are clear hazards associated with long-term HT use, many women view HT favorably for climacteric symptom relief. Media, as a source of information, is often valued as equivalent to health providers.

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