Genetic Prediction of Osteoporosis by Anti-Müllerian Hormone Levels and Reproductive Factors in Women: A Mendelian Randomization Study.

Previous observational studies have suggested that anti-Müllerian hormone (AMH) and reproductive factors are linked to reduced bone mineral density (BMD) and an increased risk of osteoporosis (OP) in women. However, related studies are limited, and these traditional observational studies may be subject to residual confounders and reverse causation, while also lacking a more comprehensive observation of various reproductive factors. Univariate and multivariate two-sample Mendelian randomization analyses were conducted to determine the causal associations of AMH levels and six reproductive factors with BMD and OP, using the random-effects inverse-variance weighted method. Heterogeneity was assessed using Cochran's Q-statistic, and sensitivity analyses were performed to identify causal correlations. Age at menarche (AAM) was negatively associated with total body BMD (TB-BMD) in females aged 45-60 and over 60 years, as well as with heel bone mineral density (eBMD). Conversely, age at natural menopause (ANM) was positively associated with TB-BMD in the same age ranges and with eBMD. ANM was only causally associated with self-reported OP and showed no significant correlation with definitively diagnosed OP. Neither AMH level nor other reproductive factors were significantly associated with a genetic predisposition to BMD at any age and OP. Later AAM and earlier ANM are significantly genetically causally associated with decreased BMD but not with OP. AMH levels, length of menstrual cycle, age at first birth, age at last birth, and number of live births, in terms of genetic backgrounds, are not causally related to BMD or OP.

Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?

BACKGROUND: Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures. METHODS: Participants were from the SWAN (Study of Women's Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution. RESULTS: The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure. CONCLUSIONS: Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.

Serum selenium and fasting blood glucose: a cross-sectional study in women of different menopause status.

BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.

High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies.

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associated with BMI in both sexes (with a larger effect size in men), whilst acylcarnitine species showed opposing associations based on sex (positive association in women and negative association in men). Finally, by utilising specific lipid ratios as a proxy for enzymatic activity, we identified stearoyl CoA desaturase (SCD-1), fatty acid desaturase 3 (FADS3), and plasmanylethanolamine Δ1-desaturase activities, as well as the sphingolipid metabolic pathway, as constituent perturbations of cardiometabolic phenotypes. Our analyses elucidate the effect of age and sex on lipid metabolism by offering a comprehensive view of the lipidomic profiles associated with common cardiometabolic risk factors. These findings have implications for age- and sex-dependent lipid metabolism in health and disease and suggest the need for sex stratification during lipid biomarker discovery, establishing biological reference intervals for assessment of disease risk.

HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition: SWAN-HDL Study.

OBJECTIVE: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. CONCLUSIONS: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

Impact of Age, Menopause, and Obesity on Oxylipins Linked to Vascular Health.

OBJECTIVE: Cardiovascular disease, a major cause of mortality and morbidity, exhibits sexual dimorphism since the onset of cardiovascular disease occurs later in women than in men. The loss of cardioprotection in older women may be due to an increase in arterial stiffness after menopause. Free fatty acid metabolites of polyunsaturated fatty acids, called oxylipins, are known to impact vessel function and may be responsible for the vascular benefits of polyunsaturated fatty acids. The objectives of this study were to compare the plasma oxylipin profiles of young females (20-55 years), older females (55+), and older males (55+) and to identify associations between oxylipins and cardiovascular disease risk factors, such as obesity and arterial stiffness. Approach and Results: We quantified plasma oxylipins by high-performance liquid chromatography-tandem mass spectrometry in archived samples taken from completed clinical trials. We identified 3 major 12-lipoxygenase products, 12-hydroxy-eicosatetraenoic acid, 12-hydroxy-eicosapentaenoic acid, and 14-hydroxy-docosahexaenoic acid, that are present at high levels in young females compared with older females and males. These oxylipins also decreased with obesity and displayed robust negative associations with arterial stiffness as assessed by brachial-ankle pulse wave velocity. According to multiple linear regression modeling, these associations were maintained even after correcting for body mass index category combined with either age, menopausal status, or estradiol levels. Using linear discriminant analysis, the combination of these 3 oxylipins effectively distinguished participants according to both brachial-ankle pulse wave velocity risk group and age. CONCLUSIONS: Higher 12-lipoxygenase oxylipin plasma concentrations associated with lower arterial stiffness in premenopausal females may be an important contributing factor to sex differences in cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01661543, NCT01562171, NCT01890330, NCT02571114 and NCT02317588.

Menopause.

This review focuses on the diagnosis and management of menopause, highlighting both hormonal and nonhormonal treatment options. In particular, the article focuses on recent data on the risks and benefits of hormone therapy to help clinicians better counsel their patients about decision making with regard to understanding and treating menopause symptoms.

Osteocalcin, ovarian senescence, and brain health.

Menopause, an inevitable event in a woman's life, significantly increases risk of bone resorption and diseases such as Alzheimer's, vascular dementia, cardiac arrest, and stroke. The sole role of bones, as traditionally regarded, is to provide structural support for skeletal muscles and allow for ambulation, however this concept is becoming quickly outdated. New literature has emerged that suggests the bone cell-derived hormone osteocalcin (OCN) plays a pivotal role in cognition. OCN levels are correlated with bone mass density and bone turnover, and thus are strongly influenced by the changes associated with menopause. The goal of the current review is to discuss potential gaps in our knowledge of OCN and cognition, discrepancies in methods of OCN quantification, and therapies to enhance circulating OCN. A discussion on implementing exercise or low frequency vibration interventions at the menopausal transition to reduce risk and severity of neurological diseases and associated cognitive decline is included.

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.

Inverse association between bone mineral density and fibrinogen in menopausal women.

OBJECTIVE: Inflammatory diseases are risk factors for osteoporosis. We aimed to explore whether fibrinogen, which is linked to chronic inflammation, is associated with bone mineral density (BMD) in menopausal women. METHODS: In this cross-sectional study, we analyzed 339 menopausal women from Zhejiang Province between January 2016 and October 2019. Linear regression analysis was performed to assess the relationship between fibrinogen and BMD. RESULTS: Significant inverse association was observed between the serum fibrinogen level and BMD in menopausal women. The mean BMD in each quartile of fibrinogen level was 0.901, 0.897, 0.892, and 0.855 g/cm2, respectively (p = 0.027). After adjusting for age, body mass index, metabolic profiles, blood inflammatory factors, and serum levels of estradiol, calcium, phosphorus, and alkaline phosphatase, fibrinogen levels remained significantly associated with BMD (regression coefficients for quartiles 1-3 vs. quartile 4 were 0.046, 0.027, and 0.036, respectively; p for trend <0.05). CONCLUSIONS: Higher fibrinogen levels were associated with lower BMD in menopausal women, which was independent of age, body mass index, estradiol, and other factors. Therefore, serum fibrinogen can be used as a new predictor of reduced BMD in menopausal women.

Can time to menopause be predicted?

Menopause represents the definite end of a woman's reproductive life and the onset of a persistent hypoestrogenic state. This postmenopausal period will for most women last several decades. Although mean menopausal age seems to have increased somewhat during the last century, there is a significant individual variation in age at natural menopause. With efficient contraception, women of reproductive age can now, to some extent, choose when they want to have children. As a consequence of this and other sociodemographic changes, age at first birth has increased significantly over the last 50 years. It is well documented that long before a woman enters the menopausal transition and subsequent menopause, fertility declines and finally ceases. Being able to predict when a woman will enter menopause would therefore, from a reproductive perspective, be of major interest. Several sociodemographic, morphometric, and endocrine factors are associated with age at menopause or time to menopause. Unfortunately the sensitivity and specificity of these in predicting time to or age at menopause are low. Therefore, with the exception of anti-Müllerian hormone measurements, either alone or in combination with chronological age close to menopause, there are as of now no reliable ways of predicting when a woman will enter menopause.

Childbearing age is correlated with components of metabolic syndrome and parameters of insulin resistance in Chinese menopausal women.

OBJECTIVE: To assess the relationship between childbearing age and elements of metabolic syndrome (MS) among menopausal women in China. MATERIALS AND METHODS: One thousand one hundred and forty-one subjects were divided into four interim average childbearing age (ACA) groups: ≥16 < 24 years old, ≥24 < 29 years old, ≥29 < 34 years old, and ≥34 years old. The group with the lowest prevalence of MS was used as a control. Body mass index, waist circumference (WC) and waist-to-hip ratio were assessed. Plasma glucose, lipids, glycated hemoglobin (HbA1c) and fasting insulin (FINS) were measured. Insulin resistance (IR) was assessed using the homeostasis model assessment (HOMA) method. RESULTS: The prevalence of MS in the 16-24 and 29-34 age groups was higher than that in the control group (p < .05). Compared with the control group, the odds ratios of MS were 1.431 for the 16-24 group (p < .05) and 1.553 for the 29-34 group (P < 0.01). ACA was correlated with FINS, HOMA-IR, WC, fasting plasma glucose, and triglycerides independent of age (p < .05). CONCLUSIONS: Average childbearing age was correlated with parameters of IR and components of MS independent of age in Chinese menopausal women.

Level of hormones in menopause in relation to diabetic retinopathy among type 2 diabetic women.

Hormonal transition among middle-aged women with type 2 diabetes may exert an impact in the development of diabetic retinopathy (DR). In this cross-sectional study, we aimed to assess the levels of estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the presence of DR and their relationship with risk factors for DR among pre- and post-menopausal women with type 2 diabetes. Serum levels of estradiol, FSH, and LH were measured using the immunoassay technique. All statistical analysis was performed using SPSS software. From the 255 participants, diabetes duration-matched, 35 premenopausal, and 57 postmenopausal women were selected for analysis. The levels of estradiol, LH, and FSH were found to be similar in participants with and without DR among pre- and post-menopausal women with diabetes. Estradiol level was not found to be related with the risk factors of DR among women with type 2 diabetes. In conclusion, female sex hormone, estradiol is not related to the presence of DR. Further prospective studies are necessary to reveal the mechanistic role of this hormone in the development of DR.

Application of Chaihu-Guizhi-Longgu-Muli decoction combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality.

To explore the application of Chaihu-Guizhi-Longgu-Muli decoction (CGLM) combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality. The data of 120 menopausal insomnia patients admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed and they were equally divided into the experimental group (n=60) and the control group (n=60) according to the order of admission. All patients were treated with Liuwei Dihuang Pills, and the experimental group was additionally given CGLM. The Pittsburgh Sleep Quality Index (PSQI), estrogen level, negative emotion score, quality of life score, serum ß-endorphin (ß-EP) level, serotonin level (5-HT) and treatment effective rate were compared between the two groups of patients. After treatment, the experimental group obtained markedly lower PSQI scores and negative emotion scores than the control group (P<0.001). The estrogen levels, ß-EP levels and 5-HT levels of the experimental group after treatment were significantly better than those of the control group (P<0.001). Higher quality of life scores and treatment effective rates were observed in the experimental group after treatment than the control group (P<0.001). CGLM combined with Liuwei Dihuang Pills can regulate the serum hormone levels of patients with menopausal insomnia, reduce negative emotions and improve sleep quality and quality of life, which merits clinical promotion.

Association between coarse particulate matter and inflammatory and hemostatic markers in a cohort of midlife women.

BACKGROUND: Exposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM2.5) exposure and CVD. Coarse particulate matter (PM10-2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain. METHODS: We examined the association between ambient concentrations of PM10-2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM10-2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM10-2.5 exposure and markers, including demographic, health and other covariates. RESULTS: Each interquartile (4 µg/m3) increase in one-year PM10-2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: - 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM10-2.5 and PAI-1 remained unchanged with adjustment for PM2.5, ozone, nitrogen dioxide, and carbon monoxide. CONCLUSIONS: Long-term PM10-2.5 exposure may be associated with changes in coagulation independently from PM2.5, and thus, contribute to CVD risk in midlife women.

Does estrogen deprivation affect pelvic floor muscle contractility?

INTRODUCTION AND HYPOTHESIS: Pelvic floor muscle (PFM) function plays a role in pelvic organ support, and estrogen deprivation is commonly seen as a risk factor for pelvic floor dysfunction. This study investigated the association between estrogen deprivation and PFM contractility. METHODS: This was a retrospective study on women attending a tertiary urogynecological unit. The assessment included an interview, POPQ assessment, Modified Oxford Scale (MOS) score, and 4D translabial ultrasound (US) on PFM contraction (PMFC). Hormonal status and details on hormone replacement therapy (HRT) were recorded. Corrected menopausal age was defined as the duration of systemic estrogen deprivation. Offline analysis of stored US volumes was performed to measure the reduction in anteroposterior hiatal diameter and bladder neck elevation on PFMC at a later date. RESULTS: Seven hundred thirty-nine women were seen during the study period. Fifty-three were excluded for missing data, leaving 686. Mean age was 56 (17-89, SD 13.3) years; average BMI was 29 (16-66, SD 6.6) kg/m²; 60.6% (n = 416) were menopausal at a mean duration of 16 (1-56, SD 10.2) years. Forty-nine (7.1%) were currently on systemic HRT, while 104 (15.2%) had used it previously. Mean corrected menopausal age (menopausal age - systemic HRT duration) was 7.4 (0-56, SD 10.0) years. Current local estrogen use ≥ 3 months was reported by 31 (4.5%). Mean PFM contractility measured by MOS was 2 (0-5, SD 1.1,). On multivariate analysis there was no association between menopausal age and PFM contractility. CONCLUSIONS: Estrogen deprivation may not be an independent predictor of pelvic floor muscle contractility.

Prolactinomas and menopause: any changes in management?

PURPOSE: Treatment goals in prolactinomas are to correct hypogonadism, restore fertility and control tumor mass in case of macroadenomas. According to current guidelines, medical treatment of asymptomatic postmenopausal women is not indicated. The purpose of this study was to review the current literature pertaining to biological behavior of prolactinomas during menopause, likelihood of successful dopamine agonist withdrawal during this period and possible prolactin-mediated increased morbidity that could modify current management. METHODS: A comprehensive literature search including papers published until July 2019 was conducted using PubMed and Medline databases. RESULTS: Women with prolactinomas entering menopause have a higher chance of prolactin normalization of treatment compared with women in their reproductive years. Although most prolactin secreting adenomas diagnosed during menopause are large, they respond well to dopamine agonist treatment. Data directly linking hyperprolactinemia with an increased risk of cancer and cardiovascular and metabolic morbidity are inconsistent. There is no data indicating that correction of hyperprolactinemia improves clinical outcomes in asymptomatic patients bearing microadenomas. CONCLUSION: There is no evidence that justifies changing current recommendations to withhold medical treatment of microprolactinomas in asymptomatic post-menopausal women. Macroprolactinoma patients should be treated according to standard clinical practice.

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.

Climacteric symptoms are related to thyroid status in euthyroid menopausal women.

BACKGROUND: Climacteric symptoms are a variety of disturbing complaints occurring during menopausal transition, many of which may be influenced by hormonal abnormalities other than related to sex steroids. AIM OF THE STUDY: In this study, we investigated the association between the intensity of climacteric symptoms measured with the Kupperman index and a thyroid status. MATERIAL AND METHODS: We evaluated by measuring serum thyrotropin (TSH), and free thyroxine (fT4) 202 euthyroid women admitted to the Department of Gynecological Endocrinology, Poznan University of Medical Sciences because of climacteric symptoms. Patients were both in perimenopause (n = 74) and postmenopause (n = 128), with no history of thyroid disorders. RESULTS: Results presented as the mean value and standard deviation were as follows: age 54.2 ± 4.9 years, BMI 26.8 ± 4.6 kg/m2, Kupperman index 26 ± 13.1 points, TSH 2.4 ± 2.6 mU/l, fT4 1.2 ± 0.37 ng/dl. We observed a negative correlation between fT4 and the time since the last menses (R = - 0.38; p = 0.02) as well as between serum TSH concentration and sweating (R = - 0.18; p = 0.03), general weakness (R = - 0.17; p = 0.03), and palpitation (R = - 0.18; p = 0.02) and a positive correlation between fT4 and nervousness (R = 0.34; p = 0.007) and palpitations (R = 0.25; p = 0.04). In the perimenopausal subgroup, there was a positive correlation between fT4 and general weakness (R = 0.42; p = 0.03), palpitations (R = 0.50; p = 0.009), and paresthesia (R = 0.46; p = 0.01). In the postmenopausal subgroup, there was a negative correlation between TSH and sweating (R = - 0.21; p = 0.03). CONCLUSIONS: Menopausal symptoms are related to thyroid status in euthyroid menopausal women.

Hormonal profile of menopausal women receiving androgen replacement therapy: a meta-analysis.

PURPOSE: Ovarian and adrenal aging leads to a progressive decline in androgen levels and deleterious effects on the quality of life. Despite this, specific replacement is not routinely recommended in the management of women with a physiological or pathological decline in their production, mainly due to the lack of long-term follow-up safety data. The purpose of this paper was to meta-analyze and summarize the existing data about hormonal profile changes in menopausal women receiving androgen replacement treatments. Full-text articles published through May 30, 2018 were found via MEDLINE and Embase and selected according to the strict inclusion criteria. METHODS: Randomized clinical trials and case-control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. 113 papers fulfilled the inclusion criteria and 56 papers were included in the analysis. Desired data were compiled and extracted by independent observers. RESULTS: Androgen administration increases E1, E2, testosterone, DHEA and DHEAS serum levels, and reduces SHBG. However, the E1 and E2 increase is evident only when DHEA is administered. CONCLUSIONS: Whatever androgen formulation we choose in postmenopausal women, the end result is a rise in testosterone serum levels. However, DHEA regimen is also associated with an increased estrogenic availability. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.