Caloric and time restriction diets improve acute kidney injury in experimental menopausal rats: role of silent information regulator 2 homolog 1 and transforming growth factor beta 1.

BACKGROUND: Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-ß1), and other indicators in the presence and absence of ovaries in AKI female rats. METHODS: The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI. RESULTS: After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-ß1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-ß1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-ß1, SIRT1, urea, creatinine, and albumin. CONCLUSION: The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-ß1 in ovary-intact animals.

Overlapping action of melatonin and female reproductive hormones-Understand the impact in pregnancy and menopause.

Melatonin is an indolamine secreted to circulation by the pineal gland according to a circadian rhythm. Melatonin levels are higher during nighttime, and the principal function of this hormone is to organize the temporal night and day distribution of physiological adaptive processes. Besides hormonal pineal production, melatonin is synthesized in various organs and tissues like the ovaries or the placenta for local utilization. In addition to its function as a circadian messenger, melatonin is also associated with many physiological functions. For example, melatonin has antioxidant properties and is involved in the regulation of energy and bone metabolism, and reproduction. Melatonin impacts several stages of reproduction and the action across the hypothalamus-pituitary-gonadal axis is well described. However, it is not well understood how those actions impact the female reproductive hormones secretion nor the consequent physiological outcomes. Thus, the first part of this chapter describes the regulation of female reproductive hormone synthesis by melatonin. Moreover, melatonin and female reproductive hormones have coincident physiological functions. Life stages like pregnancy or menopause are characterized by alterations in the reproductive hormones secretion that may be associated with certain physiological stages. Therefore, the second part discusses whether melatonin fluctuations could have an overlapping role with reproductive hormones in contributing to clinical outcomes associated with pregnancy and menopause.

Perimenopausal and Menopausal Mammary Glands In A 4-Vinylcyclohexene Diepoxide Mouse Model.

As both perimenopausal and menopausal periods are recognized critical windows of susceptibility for breast carcinogenesis, development of a physiologically relevant model has been warranted. The traditional ovariectomy model causes instant removal of the entire hormonal repertoire produced by the ovary, which does not accurately approximate human natural menopause with gradual transition. Here, we characterized the mammary glands of 4-vinylcyclohexene diepoxide (VCD)-treated animals at different time points, revealing that the model can provide the mammary glands with both perimenopausal and menopausal states. The perimenopausal gland showed moderate regression in ductal structure with no responsiveness to external hormones, while the menopausal gland showed severe regression with hypersensitivity to hormones. Leveraging the findings on the VCD model, effects of a major endocrine disruptor (polybrominated diphenyl ethers, PBDEs) on the mammary gland were examined during and after menopausal transition, with the two exposure modes; low-dose, chronic (environmental) and high-dose, subacute (experimental). All conditions of PBDE exposure did not augment or compromise the macroscopic ductal reorganization resulting from menopausal transition and/or hormonal treatments. Single-cell RNA sequencing revealed that the experimental PBDE exposure during the post-menopausal period caused specific transcriptomic changes in the non-epithelial compartment such as Errfi1 upregulation in fibroblasts. The environmental PBDE exposure resulted in similar transcriptomic changes to a lesser extent. In summary, the VCD mouse model provides both perimenopausal and menopausal windows of susceptibility for the breast cancer research community. PBDEs, including all tested models, may affect the post-menopausal gland including impacts on the non-epithelial compartments.

Exploratory metabolomic analysis for characterizing the metabolic profile of the urinary bladder under estrogen deprivation.

Background: Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from menopause, ovariectomy or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood. Methods: We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function. Results: We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance. Conclusion: This study, for the first time, depicts the metabolic landscape of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by menopause.

Estrogen-immuno-neuromodulation disorders in menopausal depression.

A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation in menopausal depressed women, immune imbalance has become a novel focus in the study of menopausal depression. In this paper, we examined the characteristics and possible mechanisms of immune imbalance caused by decreased estrogen levels during menopause and found that estrogen deficiency disrupted immune homeostasis, especially the levels of inflammatory cytokines through the ERα/ERß/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed the destruction of the blood-brain barrier, dysfunction of neurotransmitters, blockade of BDNF synthesis, and attenuation of neuroplasticity caused by inflammatory cytokine activity, and investigated estrogen-immuno-neuromodulation disorders in menopausal depression. Current research suggests that drugs targeting inflammatory cytokines and NLRP3/NF-κB signaling molecules are promising for restoring homeostasis of the estrogen-immuno-neuromodulation system and may play a positive role in the intervention and treatment of menopausal depression.

In vivo brain estrogen receptor density by neuroendocrine aging and relationships with cognition and symptomatology.

17ß-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain 18F-fluoroestradiol (18F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women's health.

Changes in cardiovascular arachidonic acid metabolism in experimental models of menopause and implications on postmenopausal cardiac hypertrophy.

Menopause is a normal stage in the human female aging process characterized by the cessation of menstruation and the ovarian production of estrogen and progesterone hormones. Menopause is associated with an increased risk of several different diseases. Cardiovascular diseases are generally less common in females than in age-matched males. However, this female advantage is lost after menopause. Cardiac hypertrophy is a disease characterized by increased cardiac size that develops as a response to chronic overload or stress. Similar to other cardiovascular diseases, the risk of cardiac hypertrophy significantly increases after menopause. However, the exact underlying mechanisms are not yet fully elucidated. Several studies have shown that surgical or chemical induction of menopause in experimental animals is associated with cardiac hypertrophy, or aggravates cardiac hypertrophy induced by other stressors. Arachidonic acid (AA) released from the myocardial phospholipids is metabolized by cardiac cytochrome P450 (CYP), cyclooxygenase (COX), and lipoxygenase (LOX) enzymes to produce several eicosanoids. AA-metabolizing enzymes and their respective metabolites play an important role in the pathogenesis of cardiac hypertrophy. Menopause is associated with changes in the cardiovascular levels of CYP, COX, and LOX enzymes and the levels of their metabolites. It is possible that these changes might play a role in the increased risk of cardiac hypertrophy after menopause.

Impact of menopause-associated frailty on traumatic brain injury.

Navigating menopause involves traversing a complex terrain of hormonal changes that extend far beyond reproductive consequences. Menopausal transition is characterized by a decrease in estradiol-17ß (E2), and the impact of menopause resonates not only in the reproductive system but also through the central nervous system, musculoskeletal, and gastrointestinal domains. As women undergo menopausal transition, they become more susceptible to frailty, amplifying the risk and severity of injuries, including traumatic brain injury (TBI). Menopause triggers a cascade of changes leading to a decline in muscle mass, accompanied by diminished tone and excitability, thereby restricting the availability of irisin, a crucial hormone derived from muscles. Concurrently, bone mass undergoes reduction, culminating in the onset of osteoporosis and altering the dynamics of osteocalcin, a hormone originating from bones. The diminishing levels of E2 during menopause extend their influence on the gut microbiota, resulting in a reduction in the availability of tyrosine, tryptophan, and serotonin metabolites, affecting neurotransmitter synthesis and function. Understanding the interplay between menopause, frailty, E2 decline, and the intricate metabolisms of bone, gut, and muscle is imperative when unraveling the nuances of TBI after menopause. The current review underscores the significance of accounting for menopause-associated frailty in the incidence and consequences of TBI. The review also explores potential mechanisms to enhance gut, bone, and muscle health in menopausal women, aiming to mitigate frailty and improve TBI outcomes.

Metabolism of progestogens used for contraception and menopausal hormone therapy.

A variety of progestogens are widely used by women for contraception and menopausal hormone therapy. The progestogens undergo extensive metabolism by oral and parenteral routes of administration to form many metabolites. Although a small number of metabolites have been shown to be biologically active, most have not been tested for biologic activity. The present review shows that we know most about progesterone metabolism, followed by the metabolism of levonorgestrel and norethindrone. Very few studies have been carried out on metabolism of most of the progestogens. The clinical significance of this deficiency is that those progestogen metabolites that bind to the progesterone receptors may also bind to other steroid receptors and be responsible for some of the well-documented side effects of administered progestogens. We also discuss how obesity and genetic polymorphisms alter progestogen metabolism, and how development of oral progestogen formulations that are targeted to the colon, where the concentration of steroid-metabolizing enzymes is much lower than in the proximal gut, may have a beneficial effect on progestogen metabolism.

Chronic Variable Stress and Cafeteria Diet Combination Exacerbate Microglia and c-fos Activation but Not Experimental Anxiety or Depression in a Menopause Model.

The menopause transition is a vulnerable period for developing both psychiatric and metabolic disorders, and both can be enhanced by stressful events worsening their effects. The present study aimed to evaluate whether a cafeteria diet (CAF) combined with chronic variable stress (CVS) exacerbates anxious- or depressive-like behavior and neuronal activation, cell proliferation and survival, and microglia activation in middle-aged ovariectomized (OVX) rats. In addition, body weight, lipid profile, insulin resistance, and corticosterone as an index of metabolic changes or hypothalamus-pituitary-adrenal (HPA) axis activation, and the serum pro-inflammatory cytokines IL-6, IL-ß, and TNFα were measured. A CAF diet increased body weight, lipid profile, and insulin resistance. CVS increased corticosterone and reduced HDL. A CAF produced anxiety-like behaviors, whereas CVS induced depressive-like behaviors. CVS increased serum TNFα independently of diet. A CAF and CVS separately enhanced the percentage of Iba-positive cells in the hippocampus; the combination of factors further increased Iba-positive cells in the ventral hippocampus. A CAF and CVS increased the c-fos-positive cells in the hippocampus; the combination of factors increased the number of positive cells expressing c-fos in the ventral hippocampus even more. The combination of a CAF and CVS generates a slight neuroinflammation process and neuronal activation in a hippocampal region-specific manner and differentially affects the behavior.

Estrogen and cardiovascular disease.

A large body of scientific research accumulated over the past twenty years documents the cardiovascular (CV) benefits of estradiol (E2) and progesterone (P4) in reproductive aged women. In contrast, accelerated development of CV disease (CVD) occurs in the absence of ovarian produced E2 and P4. Hormone replacement therapy (HRT) with E2 and P4 has been shown to cause no harm to younger menopausal women. This robust scientific data supports a reconsideration of the prescriptive use of E2 and P4 as preventative therapeutics for the reduction of CVD, even without additional large-scale studies of the magnitude of the Women's Health Initiative (WHI). With the current expanded understanding of the critical modulatory role played by E2 on a multitude of systems and enzymes impacting CVD onset, initiation of HRT shortly after cessation of ovarian function, known as the "Timing Hypothesis", should be considered to delay CVD in recently postmenopausal women.

Characteristics of the metabolically unhealthy phenotype in menopausal resistance training practitioners / Características del fenotipo metabólicamente no saludable en practicantes de entrenamiento deresistencia en la menopausia

Objective: to evaluate clinical, metabolic and body characteristics related to the metabolically unhealthy phenotype (MUH) in menopausal womenwho practice resistance training (RT).Methods: cross-sectional study with a sample of 31 women. Clinical and metabolic variables were measured. Body adiposity was assessedby body mass index, waist circumference, visceral adiposity index (VAI) and lipid accumulation product (LAP). Body composition analysis wasperformed by DEXA.Results: the prevalence of the MH phenotype was 74.2 %. Metabolically healthy (MH) women were younger, had more years of RT practice,higher HDL-c levels and lower VAI and android/gynoid ratio (A/G) than the MUH women. Women with inadequacy of HDL-c, TG, A/G and VAI had12.50 (95 % CI: 3.30-47.23), 4.83 (95 % CI: 2.37-9.85), 5.20 (95 % CI: 1.90-14.16) and 3.12 (95 % CI: 1.07-9.04) times greater prevalenceof the MUH phenotype, respectively, than those with adequacy of these parameters. Binary logistic regression analysis demonstrated that age isa predictor of the MUH phenotype (OR = 1.254; 95 % CI: 1.00-1.56) and this variable showed correlation with TG, VAI and A/G. There was noassociation between thyrotropin and MUH phenotype in the present sample.Conclusion: age and visceral adiposity are predictors for the MUH phenotype in RT practitioners in menopause, which may initially be characterized by alterations in serum lipid profile. (AU)

Objetivo: evaluar las características clínicas, metabólicas y corporales relacionadas con el fenotipo metabólicamente no saludable (MNS) enmujeres menopáusicas que practican entrenamiento de resistencia (ER).Métodos: estudio transversal con 31 mujeres. Se midieron variables clínicas y metabólicas. La adiposidad corporal se evaluó mediante el índicede masa corporal, la circunferencia de la cintura, el índice de adiposidad visceral (IAV) y el producto de acumulación de lípidos (PAL). El análisisde composición corporal fue realizado por DEXA.Resultados: la prevalencia del fenotipo metabólicamente saludable (MS) fue del 74,2 %. Las mujeres metabólicamente saludables (MS) eranmás jóvenes, tenían más años de práctica de ER, niveles más altos de HDL-c y menor IAV y relación androide/ginoide (A/G) que las mujeresMNS. Hubo asociación del fenotipo MNS con los niveles de HDL-c y A/G. Las mujeres con insuficiencia de HDL-c, TG, A/G y IAV tuvieron 12,50(IC 95 %: 3,30-47,23), 4,83 (IC 95 %: 2,37-9,85), 5,20 (IC 95 %: 1,90-14,16) y 3,12 (IC 95 %: 1,07-9,04) veces mayor prevalencia del fenotipoMNS, respectivamente, que aquellas con adecuación de estos parámetros. El análisis de regresión logística binaria demostró que la edad es unpredictor del fenotipo MUH (OR = 1,254; IC 95 %: 1,00-1,56) y esta variable mostró correlación con TG, VAI and A/G. No hubo asociación entrela tirotropina y el fenotipo MUH en la presente muestra.Conclusión: la edad y la adiposidad visceral son predictores del fenotipo MUH en practicantes de ER en la menopausia, que puede caracterizarseinicialmente alteraciones en el perfil plasmático de insípidos. (AU)

Adipocyte Metabolism and Health after the Menopause: The Role of Exercise.

Postmenopausal women represent an important target population in need of preventative cardiometabolic approaches. The loss of estrogen following the menopause eliminates protections against metabolic dysfunction, largely due to its role in the health and function of adipose tissue. In addition, some studies associate the menopause with reduced physical activity, which could potentially exacerbate the deleterious cardiometabolic risk profile accompanying the menopause. Meanwhile, exercise has adipocyte-specific effects that may alleviate the adverse impact of estrogen loss through the menopausal transition period and beyond. Exercise thus remains the best therapeutic agent available to mitigate menopause-associated metabolic dysfunction and represents a vital behavioral strategy to prevent and alleviate health decline in this population.

Sex and menopause impact 31P-Magnetic Resonance Spectroscopy brain mitochondrial function in association with 11C-PiB PET amyloid-beta load.

Increasing evidence implicates sex and endocrine aging effects on brain bioenergetic aging in the greater lifetime risk of Alzheimer's disease (AD) in women. We conducted 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) to assess the impact of sex and menopause on brain high-energy phosphates [adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi)] and membrane phospholipids [phosphomonoesters/phosphodiesters (PME/PDE)] in 216 midlife cognitively normal individuals at risk for AD, 80% female. Ninety-seven participants completed amyloid-beta (Aß) 11C-PiB PET. Women exhibited higher ATP utilization than men in AD-vulnerable frontal, posterior cingulate, fusiform, medial and lateral temporal regions (p < 0.001). This profile was evident in frontal cortex at the pre-menopausal and peri-menopausal stage and extended to the other regions at the post-menopausal stage (p = 0.001). Results were significant after multi-variable adjustment for age, APOE-4 status, midlife health indicators, history of hysterectomy/oophorectomy, use of menopause hormonal therapy, and total intracranial volume. While associations between ATP/PCr and Aß load were not significant, individuals with the highest Aß load were post-menopausal and peri-menopausal women with ATP/PCr ratios in the higher end of the distribution. No differences in Pi/PCr, Pi/ATP or PME/PDE were detected. Outcomes are consistent with dynamic bioenergetic brain adaptations that are associated with female sex and endocrine aging.

Menopause is associated with postprandial metabolism, metabolic health and lifestyle: The ZOE PREDICT study.

BACKGROUND: The menopause transition is associated with unfavourable alterations in health. However, postprandial metabolic changes and their mediating factors are poorly understood. METHODS: The PREDICT 1 UK cohort (n=1002; pre- n=366, peri- n=55, and post-menopausal females n=206) assessed phenotypic characteristics, anthropometric, diet and gut microbiome data, and fasting and postprandial (0-6 h) cardiometabolic blood measurements, including continuous glucose monitoring (CGM) data. Differences between menopausal groups were assessed in the cohort and in an age-matched subgroup, adjusting for age, BMI, menopausal hormone therapy (MHT) use, and smoking status. FINDINGS: Post-menopausal females had higher fasting blood measures (glucose, HbA1c and inflammation (GlycA), 6%, 5% and 4% respectively), sugar intakes (12%) and poorer sleep (12%) compared with pre-menopausal females (p<0.05 for all). Postprandial metabolic responses for glucose2hiauc and insulin2hiauc were higher (42% and 4% respectively) and CGM measures (glycaemic variability and time in range) were unfavourable post- versus pre-menopause (p<0.05 for all). In age-matched subgroups (n=150), postprandial glucose responses remained higher post-menopause (peak0-2h 4%). MHT was associated with favourable visceral fat, fasting (glucose and insulin) and postprandial (triglyceride6hiauc) measures. Mediation analysis showed that associations between menopause and metabolic health indicators (visceral fat, GlycA360mins and glycaemia (peak0-2h)) were in part mediated by diet and gut bacterial species. INTERPRETATION: Findings from this large scale, in-depth nutrition metabolic study of menopause, support the importance of monitoring risk factors for type-2 diabetes and cardiovascular disease in mid-life to older women to reduce morbidity and mortality associated with oestrogen decline. FUNDING: Zoe Ltd.

Cardiovascular, Metabolic and Inflammatory Changes after Ovariectomy and Estradiol Substitution in Hereditary Hypertriglyceridemic Rats.

BACKGROUND: If menopause is really independent risk factor for cardiovascular disease is still under debate. We studied if ovariectomy in the model of insulin resistance causes cardiovascular changes, to what extent are these changes reversible by estradiol substitution and if they are accompanied by changes in other organs and tissues. METHODS: Hereditary hypertriglyceridemic female rats were divided into three groups: ovariectomized at 8th week (n = 6), ovariectomized with 17-ß estradiol substitution (n = 6), and the sham group (n = 5). The strain of abdominal aorta measured by ultrasound, expression of vascular genes, weight and content of myocardium and also non-cardiac parameters were analyzed. RESULTS: After ovariectomy, the strain of abdominal aorta, expression of nitric oxide synthase in abdominal aorta, relative weight of myocardium and of the left ventricle and circulating interleukin-6 decreased; these changes were reversed by estradiol substitution. Interestingly, the content of triglycerides in myocardium did not change after ovariectomy, but significantly increased after estradiol substitution while adiposity index did not change after ovariectomy, but significantly decreased after estradiol substitution. CONCLUSION: Vascular and cardiac parameters under study differed in their response to ovariectomy and estradiol substitution. This indicates different effects of ovariectomy and estradiol on different cardiovascular but also extracardiac structures.

Body composition and cardiometabolic health across the menopause transition.

Every year, 2 million women reach menopause in the United States, and they may spend 40% or more of their life in a postmenopausal state. In the years immediately preceding menopause-known as the menopause transition (or perimenopause)-changes in hormones and body composition increase a woman's overall cardiometabolic risk. In this narrative review, we summarize the changes in weight, body composition, and body fat distribution, as well as the changes in energy intake, energy expenditure, and other cardiometabolic risk factors (lipid profile, glucose metabolism, sleep health, and vascular function), that occur during the menopause transition. We also discuss the benefits of lifestyle interventions in women in the earlier stages of menopause before these detrimental changes occur. Finally, we discuss how to include perimenopausal women in research studies so that women across the life-span are adequately represented.

Moving beyond inclusion: Methodological considerations for the menstrual cycle and menopause in research evaluating effects of dietary nitrate on vascular function.

Recent reports have acknowledged the underrepresentation of women in the field of dietary nitrate (NO3-) research. Undoubtedly, greater participation from women is warranted to clarify potential sex differences in the responses to dietary NO3- interventions. However, careful consideration for the effects of sex hormones - principally 17ß-estradiol - on endogenous nitric oxide (NO) synthesis and dietary NO3- reductase capacity is necessary for improved interpretation and reproducibility of such investigations. From available literature, we present a narrative review describing how hormonal variations across the menstrual cycle, as well as with menopause, may impact NO biosynthesis catalyzed by NO synthase enzymes and NO3- reduction via the enterosalivary pathway. In doing so, we address methodological considerations related to the menstrual cycle and hormonal contraceptive use relevant for the inclusion of premenopausal women along with factors to consider when testing postmenopausal women. Adherence to such methodological practices may explicate the utility of dietary NO3- supplementation as a means to improve vascular function among women across the lifespan.

Metabolic health, menopause, and physical activity-a 4-year follow-up study.

BACKGROUND: In women, metabolic health deteriorates after menopause, and the role of physical activity (PA) in mitigating the change is not completely understood. This study investigates the changes in indicators of metabolic health around menopause and evaluates whether PA modulates these changes. METHODS: Longitudinal data of 298 women aged 48-55 years at baseline participating in the ERMA and EsmiRs studies was used. Mean follow-up time was 3.8 (SD 0.1) years. Studied indicators of metabolic health were total and android fat mass, waist circumference, waist-to-hip ratio (WHR), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, serum total cholesterol, and high- (HDL-C) and low-density (LDL-C) lipoprotein cholesterol. PA was assessed by accelerometers and questionnaires. The participants were categorized into three menopausal groups: PRE-PRE (pre- or perimenopausal at both timepoints, n = 56), PRE-POST (pre- or perimenopausal at baseline, postmenopausal at follow-up, n = 149), and POST-POST (postmenopausal at both timepoints, n = 93). Analyses were carried out using linear and Poisson mixed-effect models. RESULTS: At baseline, PA associated directly with HDL-C and inversely with LDL-C and all body adiposity variables. An increase was observed in total (B = 1.72, 95% CI [0.16, 3.28]) and android fat mass (0.26, [0.06, 0.46]), SBP (9.37, [3.34, 15.39]), and in all blood-based biomarkers in the PRE-POST group during the follow-up. The increase tended to be smaller in the PRE-PRE and POST-POST groups compared to the PRE-POST group, except for SBP. The change in PA associated inversely with the change in SBP (-2.40, [-4.34, -0.46]) and directly with the change in WHR (0.72, [0.05, 1.38]). CONCLUSIONS: In middle-aged women, menopause may accelerate the changes in multiple indicators of metabolic health. PA associates with healthier blood lipid profile and body composition in middle-aged women but does not seem to modulate the changes in most of the studied metabolic health indicators during the menopausal transition.

Relationship between Menopause and Complications of Hyperthyroidism in Female Patients in Iraq.

Hyperthyroidism is a health problem characterized by an overactive thyroid gland, resulting in extra triiodothyronine (T3) and thyroxine (T4) production, as well as a decrease in thyroid-stimulating hormone (TSH). The oxidative stress indicators in hyperthyroid patients and the relationship with impaired metabolism of lipid are still controversial, especially in menopausal women suffering from a lack of ovulation hormones. In this study, blood samples were withdrawn from 120 subjects, including healthy premenopausal (n=30) and postmenopausal women (n=30) as control groups (G1 and G2), as well as 30 hyperthyroid women in each group of premenopausal and postmenopausal patient groups (G3 and G4). The levels of T3, T4, and TSH, blood pressure, and lipid profiles, such as triglyceride, total cholesterol (TC), high-density lipoprotein, and low-density lipoprotein, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and advanced oxidation protein products (AOPP) in the two healthy control groups and patient groups with hyperthyroidism were measured. In addition, serum progesterone levels were measured by the Bio-Merieux kit France, according to the manufacturer's instructions. The results revealed a significant decrease in SOD activity in the postmenopausal group, as compared to that in premenopausal women and control groups. Hyperthyroidism groups demonstrated a significant increase in MDA and AOPP levels, compared to control groups. Patient groups reported a decreased level of progesterone, in comparison with control groups. Moreover, there was a significant increase in T3 and T4 in patient groups (G3 and G4), compared to that in control groups (G1 and G2). There was a significant increase in systolic and diastolic blood pressure in menopausal hyperthyroidism (G4), compared to that in other groups. The TC decreased significantly in G3 and G4, compared to that in both control groups (P<0.05); nonetheless, there was no significant difference between patient groups (G3 and G4), as well as between control groups (G1 and G2). The study suggested that hyperthyroidism causes an increase in oxidative stress, which negatively affects the antioxidant system and drops levels of progesterone in both premenopausal and postmenopausal female patients. Therefore, low levels of progesterone are linked with hyperthyroidism, leading to aggravating symptoms of the disease.