Risk prediction model of metabolic syndrome in perimenopausal women based on machine learning.

INTRODUCTION: Metabolic syndrome (MetS) is considered to be an important parameter of cardio-metabolic health and contributing to the development of atherosclerosis, type 2 diabetes. The incidence of MetS significantly increases in postmenopausal women, therefore, the perimenopausal period is considered a critical phase for prevention. We aimed to use four machine learning methods to predict whether perimenopausal women will develop MetS within 2 years. METHODS: Women aged 45-55 years who underwent 2 consecutive years of physical examinations in Ninth Clinical College of Peking University between January 2021 and December 2022 were included. We extracted 26 features from physical examinations, and used backward selection method to select top 10 features with the largest area under the receiver operating characteristic curve (AUC). Extreme gradient boosting (XGBoost), Random forest (RF), Multilayer perceptron (MLP) and Logistic regression (LR) were used to establish the model. Those performance were measured by AUC, accuracy, precision, recall and F1 score. SHapley Additive exPlanation (SHAP) value was used to identify risk factors affecting perimenopausal MetS. RESULTS: A total of 8700 women had physical examination records, and 2,254 women finally met the inclusion criteria. For predicting MetS events, RF and XGBoost had the highest AUC (0.96, 0.95, respectively). XGBoost has the highest F1 value (F1 = 0.77), followed by RF, LR and MLP. SHAP value suggested that the top 5 variables affecting MetS in this study were Waist circumference, Fasting blood glucose, High-density lipoprotein cholesterol, Triglycerides and Diastolic blood pressure, respectively. CONCLUSION: We've developed a targeted MetS risk prediction model for perimenopausal women, using health examination data. This model enables early identification of high MetS risk in this group, offering significant benefits for individual health management and wider socio-economic health initiatives.

Phthalates and sex steroid hormones across the perimenopausal period: A longitudinal analysis of the Midlife Women's Health Study.

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.

Impact of Serum Vitamin D, B6, and B12 and Cognitive Functions on Quality of Life in Peri- and Postmenopausal Polish Women.

BACKGROUND Menopause initiates or accelerates health problems in a woman’s life, and affects cognitive processes and quality of life. We aimed to assess the quality of life, cognitive functions, and serum vitamin D, B6, and B12 concentrations in perimenopausal and postmenopausal Polish women. Also, we correlated the assessment of the quality of life with these vitamin concentrations and cognitive functions. MATERIAL AND METHODS The study was conducted in 287 perimenopausal and postmenopausal women. Serum levels of vitamin D, B6, and B12, cognitive functions using CNS Vital Signs software, and quality of life using WHO Quality of Life Brief were tested. RESULTS Almost all of the perimenopausal and postmenopausal women had normal concentrations of serum vitamin B12 (96%), 80% of them had normal B6 concentration, while only 9% had optimal serum vitamin D concentration. Postmenopausal women had lower Neurocognitive Index, psychomotor speed, motor speed, reaction time, and lower assessment of overall quality of life, physical health, and social relationships compared to perimenopausal women. In comparison to postmenopausal women, perimenopausal women had a lower serum vitamin B6 concentration, and the lower the concentration of this vitamin in serum they had, the lower they assessed their environment. Perimenopausal women assessed their social relationships the better, the better the visual memory, and the lower the processing speed they had. Postmenopausal women assessed the environment the better, the higher their Neurocognition Index was, and the better the reaction time they had. CONCLUSIONS Assessment of quality of life was associated with some cognitive functions in both perimenopausal and postmenopausal women.

Association between homocysteine, C-reactive protein, lipid level, and sleep quality in perimenopausal and postmenopausal women.

ABSTRACT: This study aimed to investigate the correlation between homocysteine (HCY), C-reactive protein (CRP), lipid levels, and sleep quality in perimenopausal and postmenopausal women.We collected data from 217 patients (perimenopause and postmenopausal) who visited the gynecological endocrine outpatient department of our hospital between January 2017 and January 2019. The quality and patterns of sleep were measured using the Pittsburgh Sleep Quality Index, and relationships between HCY, CRP, lipid levels, and sleep quality were analyzed according to a Pittsburgh Sleep Quality Index ≥ 8.There were significant differences in age, education level, and occupation among patients with different levels of sleep quality (P < .05). HCY, CRP, total cholesterol, triglyceride, and low-density lipoprotein levels were significantly higher in patients with poor sleep quality than in those with good sleep quality (P < .05). Age, education level, occupation, HCY, CRP, and lipid levels (total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein) were all significant influencing factors for sleep quality in perimenopausal and postmenopausal women (all P < .05). After adjusting for age, education level, occupation, HCY, and CRP levels were all significant and independent risk factors for sleep quality in perimenopausal and postmenopausal women (all P < .05).Levels of HCY, CRP, and lipids were significantly correlated with sleep quality in perimenopausal and postmenopausal women. HCY and CRP were identified as independent risk factors for sleep quality in perimenopausal and postmenopausal women, thus providing theoretical support for the clinical improvement of sleep quality.

8-Hydroxy-2'-Deoxyguanosine as an Oxidative Stress Marker in Insomnia.

We performed comparative analysis of 8-hydroxy-2'-deoxyguanosine in women in different climax stages with and without insomnia. The study involved 90 women aged 45 to 60 years divided into perimenopausal (n=30) and postmenopausal (n=60) groups. After questioning using special sleep questionnaires (Insomnia Severity Index, Epworth Sleepiness Scale, Munich Chronotype Questionnaire), the groups were divided into subgroups with insomnia and without it (control). 8-Hydroxy-2'-deoxyguanosine was assayed in blood serum by ELISA. The higher levels of 8-hydroxy-2'-deoxyguanosine in postmenopausal women with insomnia in comparison with the control and perimenopausal patients (p<0.05) attested to oxidative DNA damage in this cohort of patients.

Effects of probiotics supplementation on the hormone and body mass index in perimenopausal and postmenopausal women using the standardized diet. A 5-week double-blind, placebo-controlled, and randomized clinical study.

OBJECTIVE: The results of pioneering studies indicate that probiotics can alleviate menopausal symptoms (including cardiometabolic dysfunctions) and improve the quality of life of perimenopausal/postmenopausal women. However, the results of randomized control trials are scarce to evaluate whether the administration of probiotics could affect the balance of sex hormones during the menopause period. PATIENTS AND METHODS: In this randomized, double-blind, and placebo-controlled study, 48 perimenopausal and postmenopausal women received multispecies probiotic Sanprobi Barrier in a dose of 2.5 × 109 (CFU) for five weeks. Dietary guidelines were introduced in both groups simultaneously (~1800 kcal/per day, whole grain, no-wheat meals). The study aimed to assess the variations in follicle-stimulating hormone (FSH), estradiol (E2), cortisol (as the hypothalamic-pituitary-ovarian axis hormone), and the body mass during the intervention. RESULTS: At the endpoint, FSH level has increased significantly concerning the baseline after the probiotic intake (31.91 vs. 42.00 mIU/ml; p < 0.009). Also, in the placebo group, a strong trend to elevate FSH was observed (22.31 vs. 41.99 mIU/ml; p = 0.055). Body mass has crucially decreased in reference to the baseline in both groups (PRO: 27.90 vs. 26.30 kg/m2, p<0.001; PBO: 25.90 to 24.60 kg/m2, p<0.001). CONCLUSIONS: Probiotics affect FSH levels in perimenopausal women while simultaneously representing a non-invasive strategy to impact hormonal homeostasis. They could potentially have an impact on cardiometabolic health.

Association between high normal-range thyrotropin concentration and carotid intima-media thickness in euthyroid premenopausal, perimenopausal and postmenopausal women.

OBJECTIVE: There are currently no established cutoff levels for thyrotropin (TSH) within the reference intervals associated with carotid atherosclerosis to prevent the onset of cardiovascular diseases. The present study aimed to determine the TSH cutoff level associated with carotid maximum intima-media thickness (max IMT) in euthyroid premenopausal, perimenopausal and postmenopausal women. STUDY DESIGN: We conducted a cross-sectional study of 468 euthyroid women who had not been treated for or diagnosed with cardiovascular diseases and/or metabolic disorders among 1221 Japanese women who participated in a comprehensive medical examination at the Hidaka Hospital, Japan. Participants' weight, blood pressure, plasma glucose, serum lipoprotein, free thyroxine and TSH were measured and an interview about menstruation was conducted. Carotid ultrasonography was performed to determine max IMT. RESULTS: Max IMT significantly increased stepwise as menopausal status progressed (p < 0.001). Serum TSH levels were significantly higher in participants with carotid plaques, defined as max IMT ≥1.1 mm (p = 0.038), and were independently associated with the presence of carotid plaque using multivariate logistic regression analysis (ß =1.218, p = 0.036). In postmenopausal women, significantly higher carotid max IMT values were observed in women with serum TSH ≥2.5 µIU/mL compared with women with concentrations <2.5 µIU/mL (p = 0.018) without elevated total cholesterol and low-density lipoprotein cholesterol concentrations. These differences were not observed in premenopausal women. CONCLUSIONS: Laboratory finding of serum TSH concentration ≥2.5 µIU/mL may be useful to assess risk of atherosclerosis, especially in postmenopausal women.

Correlative Study of Bone-related Biochemicals and Endocrine Changes in Perimenopausal Women in Enugu, Nigeria.

BACKGROUND AND OBJECTIVE: Perimenopause is a physiological occurrence in women, and is characterized by endocrine and biochemical changes. During perimenopause phase, many derangements or abnormal health conditions start developing as a result of hormonal changes. These derangements in health conditions and biochemical changes lead to higher incidence of metabolic syndrome (MetS) occurrence with or without bone involvement. There is a scarcity of information on MetS in Enugu, Southern Nigeria and there is no available data on the correlation of selected bone-related biochemicals with endocrine parameters and MetS in perimenopausal women from the region. MATERIAL AND METHODS: We consecutively sampled 200 apparently healthy women, and categorized them into 120 perimenopausal women (age (!) = 50years) and a second group of 80 women in premenopause (age (!) = 35years). Measurement of anthropometric indices like blood pressure, height, weight and waist circumference were taken. Fasting blood samples were collected for the estimation of endocrine parameters (estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH)) using enzyme linked immunosorbent assay (ELISA) technique. The lipid profile, fasting plasma glucose (FPG), uric acid, inorganic phosphate, calcium and alkaline phosphatase levels were determined using standard biochemical methods. The evaluation of MetS was carried out in the women using the three different criteria: World Health Organization (WHO), National Cholesterol Education Program- Adult Treatment Panel 111 (NCEP-ATP 111) and International Diabetes Federation (IDF). For statistical analysis, Student's t-test, Pearson correlation and Chi-square were used to compare categorical and continuous variables. RESULTS: Calcium was predominantly high in the three criteria (p<0.05). LH and FSH showed a positive correlation with FPG while E2 was negatively associated with FPG. Similarly, LH showed a positive association with inorganic phosphate while E2 was negatively associated with alkaline phosphatase (p<0.05). CONCLUSION: Perimenopausal women are at higher risk of developing osteoporosis than premenopausal women. This emphasizes the need for timely diagnosis of osteoporosis in perimenopausal women.

Effects of menstrual cycle and menopause on internal carotid artery shear-mediated dilation in women.

This study aimed to elucidate the effects of change in estrogen during the menstrual cycle and menopause on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation of the ICA and serum estradiol were measured in 11 premenopausal (Pre-M, 21 ± 1 yr), 13 perimenopausal (Peri-M, 49 ± 2 yr), and 10 postmenopausal (Post-M, 65 ± 7 yr) women. Measurements were made twice within the Pre-M group at their early follicular (EF, lower estradiol) and late follicular (LF, higher estradiol) phases. Shear-mediated dilation was induced by 3 min of hypercapnia (target PETCO2 + 10 mmHg from individual baseline) and was calculated as the percent rise in peak diameter relative to baseline diameter. ICA diameter and blood velocity were simultaneously measured by Doppler ultrasound. In Pre-M, shear-mediated dilation was higher during the LF phase than during the EF phase (P < 0.01). Comparing all groups, shear-mediated dilation was reduced across the menopausal transition (P < 0.01), and Pre-M during the LF phase showed the highest value (8.9 ± 1.4%) compared with other groups (Pre-M in EF, 6.4 ± 1.1%; Peri-M, 5.5 ± 1.3%; Post-M, 5.2 ± 1.9%, P < 0.05 for all). Shear-mediated dilation was positively correlated with serum estradiol even after adjustment of age (P < 0.01, r = 0.55, age-adjusted; P = 0.02, r = 0.35). Collectively, these data indicate that controlling the menstrual cycle phase is necessary for the cross-sectional assessments of shear-mediated dilation of the ICA in premenopausal women. Moreover, current findings suggest that a decline in cerebrovascular endothelial function may be partly related to the reduced circulating estrogen levels in peri- and postmenopausal women.NEW & NOTEWORTHY The present study evaluated the effects of the menstrual cycle and menopause stages on the shear-mediated dilation of the ICA, a potential index of cerebrovascular endothelial function, in pre-, peri-, and postmenopausal women. Shear-mediated dilation of the ICA was increased from the low- to high-estradiol phases in naturally cycling premenopausal women and was reduced with advancing menopause stages. Furthermore, lower estradiol was associated with reduced shear-mediated dilation of the ICA, independent of age.

IL-6 Response to Psychosocial Stress Predicts 12-month Changes in Cardiometabolic Biomarkers in Perimenopausal Women.

OBJECTIVE: Cardiometabolic diseases are the number one cause of mortality, accounting for over one third of all deaths in the United States. Cardiometabolic risk further increases with psychosocial stress exposure and during menopausal transition in women. Because disease risk and stress burden are associated with aberrant immune signaling, we hypothesized that responses of interleukin-6 (IL-6) to psychosocial stress may predict longitudinal cardiometabolic outcomes in perimenopausal women. METHODS: We conducted post hoc analyses in 151 perimenopausal or early postmenopausal women participants in a previously completed study. At study onset, participants underwent the Trier Social Stress Test (TSST), and plasma IL-6 was measured repeatedly before and during the 1 hour post-TSST. Subsequently, participants were randomly assigned to either hormonal treatment (HT) or placebo and followed for 12 months to determine longitudinal changes in cardiometabolic biomarkers. RESULTS: Greater IL-6 reactivity to stress, measured with baseline-adjusted area under the curve, predicted 12-month decrease in flow-mediated dilatation of the brachial artery (P = 0.0005), a measure of endothelial-dependent vascular function, but not in endothelial-independent function measured with nitroglycerin-mediated dilatation (P = 0.17). Greater baseline IL-6 levels predicted 12-month increase in insulin resistance based on the homeostatic model assessment of insulin resistance score (P = 0.0045) and in the number of criteria met for metabolic syndrome (P = 0.0008). These predictions were not moderated by HT. CONCLUSIONS: Greater baseline IL-6 levels as well as its reactivity to stress may predict worsening in distinct cardiometabolic biomarkers as women transition to menopause. Interleukin-6 reactivity predicts decline in endothelial-dependent vascular function, whereas baseline IL-6 presages accumulation of metabolic risk.

Association analysis between vitamin D level and depression in women perimenopause: A protocol of systematic review and meta-analysis.

BACKGROUND: In recent decades, many researches manifested that the perimenopause is a window of vulnerability for the development of both depressive symptoms and major depressive episodes. Some scholar thought that those women diagnosed with depression may be particularly sensitive to changes in the hormonal milieu experienced premenstrual, during the postpartum period or during the menopause transition in. Risk factors for depressive symptoms during the perimenopause include prior standardized mean difference (MDD), psychosocial factors, anxiety symptoms, and reproductive-related mood disturbance. However, active vitamin D (VD), exerts protective and regulatory effects on the brain dopamine system and suggests that similar to the antidepressant. Therefore, serum 25(OH)D level may be negatively correlated with the perimenopausal depression. METHODS: The study only selects clinical randomized controlled trials of depression in perimenopausal women. We will search each database from the built-in until October 2020. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and grey literature. Two researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk, and the continuous is expressed by mean difference or standard mean difference, eventually the data is synthesized using a fixed effect model or a random effect model depending on the heterogeneity. The serum vitamin D level, Hamilton Depression Scale, or Beck Depression Inventory or Zung self-rating depression scale or patient health questionnare-9 were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3. RESULTS: This meta-analysis will further determine the association analysis between VD level and depression in women perimenopause. CONCLUSION: This study determines the VD level is related to the occurrence of depression in perimenopausal women.

Optimized integration of fluoxetine and 7, 8-dihydroxyflavone as an efficient therapy for reversing depressive-like behavior in mice during the perimenopausal period.

Fluoxetine (FLX) has been considered as an effective anti-depressant drug. Besides, previous studies reported reasonable anti-depressant effects for 7, 8-dihydroxyflavone (7, 8 DHF). However, the combination of FLX and 7, 8 DHF in a well-established depression model has not been explored. In this study, we demonstrate that the 7, 8 DHF can improve the anti-depressant efficacy of FLX in a chronic unpredictable mild stress (CUMS)-induced depression during the perimenopausal period. The corresponding mechanism of FLX+7, 8 DHF therapy and the effect of ANA-12 are also investigated. Moreover, the influences of 7, 8 DHF (5 mg/kg/day), FLX (18 mg/kg/day), and ANA-12 (0.5 mg/kg/day) on a depressive-like behavior are displayed. Inflammatory, autophagic and apoptotic changes of hippocampus and cortex are examined by using western blot, immunofluorescence, and Real-Time Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) techniques. The protein levels of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/phosphorylated extracellular signal-regulated kinase1/2 (p-ErK 1/2)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) of hippocampus and cortex are assessed by western blot. The combined FLX and 7, 8 DHF treatment can significantly improve depressive-like behavior in sucrose preference and forced swimming tests accompanied by a noticeable upregulation of autophagy, neuronal nuclei (NeuN), ionized calcium-binding adaptor molecule 1 (Iba1) expressions, and PI3K/Akt/ mTOR/ p-ErK 1/2 signaling pathways. Besides, an obvious increase of the brain-derived neurotrophic factor (BDNF) and TrkB levels are observed with down-regulated inflammation and apoptosis. These findings suggest that the integrated FLX and 7, 8 DHF holds a potential as an efficient treatment to ameliorate depressive-like behavior in perimenopausal patients.

Serum adiponectin is a potential biomarker for metabolic syndrome in peri-and postmenopausal women.

Metabolic syndrome (MetS) increases its prevalence during menopausal period and there is no appropriate marker for screening before the cardiovascular damage begun. This study aims to find the diagnostic accuracy and the appropriate cutoff level of serum adiponectin for the screening of MetS in peri- and postmenopausal women. Women aged at least 40 years old attending health checkup clinic were recruited. Anthropometric measurements, blood pressure, MENQOL, and blood chemistry (glucose, adiponectin, HDL-C, LDL-C, and TG) were recorded. MetS was defined by JIS 2009 criteria. 290 peri-and postmenopausal women mean age 54.25 ± 8.6 years were recruited. 66% was postmenopause and 21.4% of them has MetS. The socioeconomic and lifestyle factors seem similar among women with and without MetS. In the participants with MetS, the prevalence of abdominal obesity was higher (96.8% vs 49.6%, p < .001, respectively) and more prevalence of android fat distribution pattern was observed (76.2% vs 36%, p < .001, respectively). Serum adiponectin was significantly lower in women with MetS (6.0 ± 4.6 vs 9.2 ± 5.2 µg/mL, p < .001 in MetS and non-MetS, respectively). Serum adiponectin is a good biomarker for MetS and we recommend the cutoff level of serum adiponectin lower than 7.15 µg/mL for screening of MetS (AUC (95% CI) of = 0.72 (0.64-0.79), p < .001).

Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism.

BACKGROUND: Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms. OBJECTIVE: To measure serum levels of markers related to adiposity, inflammation/angiogenesis and digestive metabolism and correlate them with body mass index (BMI), waist-to-hip ratio (WHR), metabolic parameters and menopausal symptoms (assessed with the 10-item Cervantes Scale [CS-10]). METHODS: Serum of perimenopausal women (n = 24), STRAW stages-2 and -1, was analyzed using the Bio-Plex 200 System technology to assess 30 proposed analytes. The MetS was defined by the American Heart Association criteria and women were divided as: normal BMI (NBMI), excessive BMI (EBMI), and EBMI with MetS (EBMI-MetS). RESULTS: Weight, BMI, abdominal circumference, WHR, systolic blood pressure, glucose and triglyceride levels were significantly higher and high-density lipoprotein cholesterol (HDL-C) was lower in EBMI-MetS women compared to NBMI ones. Insulin, C-peptide, resistin, adipsin, GIP, leptin, IL-6, FGF21 and PAI-1 levels were significantly higher and ghrelin and IGFBP-1 lower in EBMI-MetS women as compared to NBMI ones. Spearman's correlation of pooled data showed a significant positive correlation between abdominal perimeter and WHR and C-peptide, insulin, adipsin, resistin, leptin, PAI-1 and FGF21 and a negative correlation with IGFBP-1 levels. Total CS-10 scores and hot flush intensity did not differ between studied groups, yet positively correlated with anthropometric values but not with studied analytes. CONCLUSION: Perimenopausal women with EBMI and the MetS showed an altered metabolic profile, but no differences in menopausal symptoms which also did not correlate with changes in studied biomarkers.

Comparison of low dose versus ultra-low dose hormone therapy in menopausal symptoms and quality of life in perimenopause women.

The study was to compare the efficacy, safety, and tolerability of low dose versus ultra-low dose hormone therapy (HT) in the management of perimenopause symptoms and quality of life. Retrospective analysis of perimenopause patients prescribed for 25 weeks HT in the outpatient clinic of menopause. A total of 132 perimenopause women were included in two treatment regimens: one with low dose HT (LD-HT) and one with ultra-low dose HT (ULD-HT). Changes in serum levels of follicle-stimulating hormone, estradiol as well as transvaginal ultrasound (TVUS), the 36-item Short Form Health Survey (SF-36), the Kupperman Index (KI), and adverse effects were assessed at baseline, 4, 13, and 25 weeks. By the end of 25 weeks of treatment, each score of SF-36 domains for both LD-HT and ULD-HT groups were increased, the KI decreased, and the endometrial thickness increased in both groups and there was no statistical difference between two groups. Both groups have negligible differences in incidence of adverse effects. Low dose and ultra-low dose HT both can serve in improving symptoms of perimenopause, thereby offering a better quality of life with decreased incidence of side effects. Ultra-low dose treatment may have a better advantage on safety and tolerance.

Relationship between serum homocysteine and different menopausal stage.

Objective: This study aimed to investigate the serum level of homocysteine in menopausal women and to explore the association between menopausal status, blood lipids, and homocysteine concentrations.Methods: The study recruited females aged 40-60 years who were not receiving menopausal hormone therapy. The demographic characteristics and menopausal status of the women were collected in the form of questionnaires. The study analyzed the association between hyperhomocysteinemia and variables using binary logistic stepwise regression.Results: Among 366 enrolled subjects, menopausal status was divided into four stages: premenopause stage (n = 135), menopausal transition stage (n = 91), early postmenopause stage (n = 87), and late postmenopause stage (n = 53). The proportion of hyperhomocysteinemia in the premenopausal stage, menopausal transition stage, and postmenopausal stage was 43%, 26.4%, and 45%, respectively (χ2 = 8.999, p = 0.011). The mean concentration of homocysteine was 9.75 µmol/l. The level of homocysteine was higher in the postmenopause stage than in the other stages (p = 0.043), and the difference between postmenopause and menopausal transition was statistically significant (p < 0.01). In the binary logic analysis, menopausal transition compared with postmenopause (odds ratio = 2.027, 95% confidence interval = 1.117-3.679, p = 0.005).Conclusions: Serum homocysteine levels are associated with menopausal status. Homocysteine concentrations were progressively higher across menopausal stages. The transformation in the female body across the menopause transition stages may cause elevations in the homocysteine level in postmenopausal women.

The Effect of Perimenopausal Transdermal Estradiol and Micronized Progesterone on Markers of Risk for Arterial Disease.

BACKGROUND: The arterial effects of hormone therapy remain controversial. This study tested the effects of transdermal estradiol plus intermittent micronized progesterone (TE + IMP) in healthy perimenopausal and early postmenopausal women on several mechanisms involved in the pathophysiology of arterial disease. METHODS: Healthy perimenopausal and early postmenopausal women, ages 45 to 60 years, were enrolled in this randomized, double-blind, placebo-controlled trial. Women were randomized to receive TE (0.1 mg/day) + IMP (200 mg/day for 12 days) or identical placebo patches and pills for 12 months. Outcomes included: change in stress reactivity composite z-score (combining inflammatory, cortisol, and hemodynamic responses to a standardized psychological laboratory stressor); flow-mediated dilation (FMD) of the brachial artery (an index of vascular endothelial function); baroreflex sensitivity; and metabolic risk (presence of the metabolic syndrome or insulin resistance), all assessed at baseline and at months 6 and 12. RESULTS: Of 172 women enrolled, those assigned to TE + IMP tended to have higher resting baroreflex sensitivity than those assigned to placebo across the 6- and 12-month visits. Although treatment groups did not differ in terms of the other prespecified outcomes, a significant treatment-by-age interaction was found for FMD and stress reactivity such that an age-related decrease in FMD and increase in stress reactivity were seen among women assigned to placebo but not those assigned to TE + IMP. Women on TE + IMP also had lower resting diastolic blood pressure, lower levels of low-density lipoprotein cholesterol, and higher baroreflex sensitivity during stress testing. CONCLUSIONS: TE + IMP tended to improve cardiac autonomic control and prevented age-related changes in stress reactivity and endothelial function among healthy perimenopausal and early postmenopausal women.

Plasma Cytokine Levels in Overweight Versus Obese Disease-Free Perimenopausal Women.

OBJECTIVE: To evaluate the plasma cytokine levels during T cell-mediated inflammatory responses and compare the metabolic markers between overweight and obese perimenopausal women without systemic diseases. METHODS: Sixty perimenopausal women were divided into two groups (overweight and obese). Participants in both groups had their waist-to-height ratio (WHtR) measured and blood samples collected for the evaluation of estradiol, fasting glucose, leptin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10, IL-17A levels, and lipid profile. RESULTS: In univariate analysis, women with obesity showed increased WHtR, fasting glucose, leptin, and IL-6 (p < 0.05) levels; however, significant differences were not observed in IL-10 or IL-17A (p > 0.05) levels. In the receiver operating characteristic curve, the highest areas under the curve were shown for leptin (0.856) and IL-6 (0.706). IL-6 levels correlated with both hs-CRP (r = 0.302, p = 0.020) and leptin (r = 0.294, p = 0.022). However, in multivariate analysis, IL-6 was not associated with a greater likelihood of obesity (OR = 1.61; 95% CI: 0.82-3.15; p = 0.16), when potential confounders were considered. CONCLUSION: IL-6 levels varied between overweight and obese perimenopausal women, and this association was weaker when adjusted for other clinical variables.

Impact of Estradiol Variability and Progesterone on Mood in Perimenopausal Women With Depressive Symptoms.

CONTEXT: Women are at increased risk for depressive symptoms during the menopause transition. Changes in estradiol secretion and presence of vasomotor symptoms (VMS) contribute to perimenopausal depressive symptoms, but links with progesterone have not been investigated. OBJECTIVE: To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology. DESIGN AND INTERVENTION: Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models. SETTING: Academic medical center. PATIENTS: Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 15.5 ± 5.3). MAIN OUTCOME MEASURE: Depressive symptoms (MADRS score). RESULTS: During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (ß = 0.11 [95% confidence interval (95% CI), 0.04 to 0.18; P = 0.001]; ß = -2.62 [95% CI, -4.52 to -0.71; P = 0.007], respectively), after accounting for higher body mass index, lifetime history of depression, and stressful life events. CONCLUSIONS: Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.

Effects of red clover (Trifolium pratense) isoflavones on the lipid profile of perimenopausal and postmenopausal women-A systematic review and meta-analysis.

AIM: The aim of this systematic review and meta-analysis was to clarify the effect of a specific standardised extract of red clover (Trifolium pratense) on the lipid profile of perimenopausal and postmenopausal women. METHODS: Medline (PubMed), EMBASE, and Cochrane Library electronic databases were searched for papers in English reporting randomized controlled trials published up to 2017. Reference lists from those papers were checked for further relevant publications. Studies were identified and reviewed for their eligibility for inclusion in this review. The changes from baseline in the levels of individual components of the lipid profiles were used to assess differences between the active treatment and placebo groups. Weighted mean differences and 95 % confidence intervals were calculated for continuous data using a random-effects model. RESULTS: Ten eligible studies (twelve comparisons) with 910 peri- and postmenopausal women were selected for systematic review. The meta-analysis showed changes in serum levels: total cholesterol, -0.29 (95 % CI: -0.53 to -0.06) mmol/L [-11.21 (95 % CI: -20.49 to -13.92) mg/dL], p = 0.0136; LDL-cholesterol, -0.13 (95 % CI: -0.35 to 0.09) mmol/L [-5.02 (95 % CI: -13.53 to 3.48) mg/dL], p = 0.2418; triglycerides, -0.15 (95 % CI: -0.32 to 0.01) mmol/L [-13.28 (95 % CI: -28.34 to 0.88) mg/dL], p = 0.0592; and HDL-cholesterol, 0.14 (95 % CI: -0.08 to 0.36) mmol/L [5.41 (95 % CI: -3.09-13.92) mg/dL], p = 0.2103. TheI2 statistic ranged from 87.95%-98.30 %, indicating significant heterogeneity. CONCLUSIONS: The results suggest that a red clover extract is efficacious in reducing the concentrations of total cholesterol; however, changes in HDL-C, LDL-C and triglycerides are not as pronounced. Potentially, this means that women takingTrifolium pratense for menopausal symptoms can derive additional benefits from the plant's specific effect that corrects abnormal cholesterol levels. Additional studies are needed to assess its effects on post-menopausal women.