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.

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).

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.

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.

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.

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.

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.

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.

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.

Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease according to Different Menstrual Status Groups.

Objective: The present study aimed to explore the association between SUA and NAFLD in women with different menstrual statuses. Methods: A total of 6043 women were selected from the Jidong and Kailuan communities for inclusion in the present study. The SUA levels of participants were divided into quartiles. NAFLD was determined by abdominal ultrasonography. Data from laboratory tests and clinical examination were collected, and basic information was obtained from standardized questionnaires. The menstrual status was stratified into menstrual period, menopause transition period, and postmenopause. Multivariate logistic regression models were used to determine the relationship between menstrual status, SUA, and NAFLD. Results: The levels of SUA in subjects with NAFLD in the menstrual period, menopause transition period, and postmenopause were 268.0 ± 71.1, 265.6 ± 67.8, and 286.7 ± 75.8 (mmol/L), respectively, and were higher than those in subjects without NAFLD. The adjusted odds ratios (ORs) with 95% confidence interval (CI) for NAFLD among participants in the menopause transition period and postmenopausal period were 1.10 (0.89-1.37) and 1.28 (1.04-1.58), respectively, compared with the menstrual period women. Compared to the lowest quartile of SUA, the adjusted ORs with 95% CI of the highest quartile for NAFLD were 2.24 (1.69-2.99) for females in the menstrual period, 1.92 (1.10-3.37) for females in the menopause transition period, and 1.47 (1.06-2.03) for females in postmenopause. Conclusions: Menstrual status was significantly correlated with NAFLD. High levels of SUA were associated with NAFLD in females during the three menstrual periods.

Endocrine profile of the VCD-induced perimenopausal model rat.

During the transition to menopause, women experience a variety of physical and psychological symptoms that are directly or indirectly linked to changes in hormone secretion. Establishing animal models with intact ovaries is essential for understanding these interactions and finding new therapeutic targets. In this study, we assessed the endocrine profile, as well as the estrous cycle, in the 4-vinylcyclohexene diepoxide (VCD)-induced follicular depletion rat model in 10-day intervals over 1 month to accurately establish the best period for studies of the transition period. Twenty-eight-day-old female rats were injected daily with VCD or oil s.c. for 15 days and euthanized in the diestrus phase approximately 70, 80, 90 and 100 days after the onset of treatment. The percentage of rats showing irregular cycles and the plasma level of FSH increased only in the 100-day VCD group. Plasma anti-Müllerian hormone (AMH) and progesterone were lower in all VCD groups compared to control groups, while estradiol remained unchanged or higher. As in control groups, dihydrotestosterone (DHT) progressively decreased in the 70-90-day VCD groups; however, it was followed by a sharp increase only in the 100-day VCD group. No changes were found in plasma corticosterone, prolactin, thyroid hormones or luteinizing hormone. Based on the estrous cycle and endocrine profile, we conclude that 1) the time window from 70 to 100 days is suitable to study a perimenopause-like state in this model, and 2) regular cycles with low progesterone and AMH and normal FSH can be used as markers of the early/mid-transition period, whereas irregular cycles associated with higher FSH and DHT can be used as markers of the late transition period to estropause.

Retrospective evaluation of 99th percentile hCG results to adjust clinical decision points.

While accurate measurement of chorionic gonadotropin (hCG) is necessary, so are appropriate clinical decision points (CDPs) for patients of all ages. The CDP for hCG is intended to identify early pregnancy in patients of child bearing age; non-pregnant patients who are older frequently yield hCG results > 5 IU/L, making the use of a low hCG CDP problematic for these patients. Using a retrospective review of all hCG results generated over a 32-month period, 8507 hCG results from non-pregnant females of all ages were analyzed. Patients < 40 years of age comprised 74% of hCG measurements, and produced hCG results ≥ 5 IU/L 1% of the time, but this frequency increased in patients 40-49 (17% of hCG results; 4% ≥5 IU/L) and ≥50 (9% of hCG results; 20% ≥ 5 IU/L). While only 3% of hCG results were ≥5 IU/L in the overall data set, all (24/24) of hCG results 10-14 IU/L came from patients ≥ 40 years of age and all (3/3) hCG results ≥ 15 IU/L came from patients ≥ 50 years of age. The 99th percentile hCG results in the population were 3 IU/L in patients < 40, 7 IU/L in patients 40-49, and 13 IU/L in patients ≥ 50 years of age. These findings demonstrate a progressive increase in measurable hCG correlating to patient age and demonstrate a proof-of-concept that institutions could assess 99th percentile hCG results to assign more appropriate method-dependent CDPs to different age groups.