-
Psychoneuroendocrinology Dec 2023Medial temporal lobe (MTL) atrophy is correlated with risk and severity of Alzheimer disease (AD) pathology and cognitive decline. Increasing evidence suggest that...
Medial temporal lobe (MTL) atrophy is correlated with risk and severity of Alzheimer disease (AD) pathology and cognitive decline. Increasing evidence suggest that oestrogens affect the aging of MTL structures. Here we investigate the relationship between reproductive hormone exposure, polygenic scores for AD risk and oestradiol concentration, MTL anatomy and cognitive performance in postmenopausal women. To this end, we used data from 10,924 female participants in the UK Biobank from whom brain MRI and genetic data were available. We fitted linear regression models to test whether the volume of structures comprising the MTL were predicted by a) timing related to menopause, b) the use and timing of hormone replacement therapy (HRT) and c) polygenic scores for AD risk and oestradiol concentration. Results showed that longer use of HRT was associated with larger parahippocampal volumes (2.53 mm/year, p = 0.042). A later age of natural menopause, and a longer reproductive span, was associated with larger hippocampal (6.08 and 5.72 mm/year, p = 0.0006 and 0.0005), parahippocampal (4.17 mm and 4.19 mm/year, p = 0.00006 and 0.00001), amygdala (2.10 and 2.22 mm/year, p = 0.028 and 0.01) and perirhinal cortical (2.56 and 2.95 mm/year, p = 0.028 and 0.008) volumes. Superior prospective memory performance was associated with later age at natural menopause, and a longer reproductive span (ß = 0.05 and 0.05 respectively, p = 0.019 and 0.019). Polygenic scores for AD risk and for oestradiol concentration were not associated with MTL volume and did not interact with menopause-related factors to affect MTL structure. Our results suggest that HRT use did not have any detrimental effects on cognition or brain structure, whilst greater exposure to reproductive hormones across time is associated both with slightly larger volumes of specific MTL structures and marginally superior memory performance, independent of genetic risk for AD and genetic predisposition for higher oestradiol levels. However, the clinical utility of maintenance of oestrogens post-menopause for brain health and protection against cognitive decline is curtailed by the small effect sizes observed.
Topics: Humans; Female; Postmenopause; Duration of Therapy; Temporal Lobe; Alzheimer Disease; Menopause; Magnetic Resonance Imaging; Estrogens; Estradiol
PubMed: 37774659
DOI: 10.1016/j.psyneuen.2023.106393 -
Journal of Ovarian Research Jul 2023Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI... (Review)
Review
Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI primarily manifests as ovarian function decline and endocrine disorders in women prior to age 40 and is an established cause of female infertility. It is crucial to elucidate the causative factors of POI, not only to expand the understanding of ovarian physiology, but also to provide genetic counselling and fertility guidance to affected patients. Factors leading to POI are multifaceted with genetic factors accounting for 7% to 30%. In recent years, an increasing number of DNA damage-repair-related genes have been linked with the occurrence of POI. Among them, DNA double-strand breaks (DSBs), one of the most damaging to DNA, and its main repair methods including homologous recombination (HR) and non-homologous end joining (NHEJ) are of particular interest. Numerous genes are known to be involved in the regulation of programmed DSB formation and damage repair. The abnormal expression of several genes have been shown to trigger defects in the overall repair pathway and induce POI and other diseases. This review summarises the DSB-related genes that may contribute to the development of POI and their potential regulatory mechanisms, which will help to further establish role of DSB in the pathogenesis of POI and provide theoretical guidance for the study of the pathogenesis and clinical treatment of this disease.
Topics: Humans; Female; Adult; DNA Breaks, Double-Stranded; Menopause, Premature; Primary Ovarian Insufficiency; Fertility; Infertility, Female
PubMed: 37430352
DOI: 10.1186/s13048-023-01221-2 -
Maturitas Dec 2023Aging is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females... (Review)
Review
Aging is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females demonstrate a distinct pattern of muscle aging compared to males, potentially due to menopause, when the production of endogenous sex hormones declines. This systematic review aims to investigate the current knowledge about the role of estrogen in female skeletal muscle aging. A systematic search of MEDLINE Complete, Global Health, Embase, PubMed, SPORTDiscus, and CINHAL was conducted. Studies were considered eligible if they compared a state of estrogen deficiency (e.g. postmenopausal females) or supplementation (e.g. estrogen therapy) to normal estrogen conditions (e.g. premenopausal females or no supplementation). Outcome variables of interest included measures of skeletal muscle mass, function, damage/repair, and energy metabolism. Quality assessment was completed with the relevant Johanna Briggs critical appraisal tool, and data were synthesized in a narrative manner. Thirty-two studies were included in the review. Compared to premenopausal women, postmenopausal women had reduced muscle mass and strength, but the effect of menopause on markers of muscle damage and expression of the genes involved in metabolic signaling pathways remains unclear. Some studies suggest a beneficial effect of estrogen therapy on muscle size and strength, but evidence is largely conflicting and inconclusive, potentially due to large variations in the reporting and status of exposure and outcomes. The findings from this review point toward a potential negative effect of estrogen deficiency on aging skeletal muscle, but further mechanistic evidence is needed to clarify its role.
Topics: Male; Female; Humans; Quality of Life; Estrogens; Aging; Menopause; Muscle, Skeletal
PubMed: 37716136
DOI: 10.1016/j.maturitas.2023.107844 -
Revista Da Associacao Medica Brasileira... 2024
Topics: Female; Humans; Melatonin; Thyroid Gland; Menopause; Menstrual Cycle
PubMed: 38511761
DOI: 10.1590/1806-9282.701EDIT -
PLoS Medicine Dec 2023Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the... (Observational Study)
Observational Study
BACKGROUND
Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently.
METHODS AND FINDINGS
Nested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur.
CONCLUSIONS
Use of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk.
Topics: Female; Humans; Case-Control Studies; Central Nervous System Neoplasms; Denmark; Estrogen Replacement Therapy; Estrogens; Glioma; Meningeal Neoplasms; Meningioma; Menopause; Progestins; Risk Factors; Middle Aged
PubMed: 38113227
DOI: 10.1371/journal.pmed.1004321 -
Post Reproductive Health Jun 2024Menopause marks the end of female reproductive capacity. It is defined as the point after cessation of the menstrual cycle for 12 months (Nursat et al., 2008)....
Menopause marks the end of female reproductive capacity. It is defined as the point after cessation of the menstrual cycle for 12 months (Nursat et al., 2008). Awareness about menopause has increased over the last decade, yet studies have shown that women still lack knowledge regarding the subject. Likewise, awareness of women between the age of 40-65 on the potential role of physical activity prior to and during menopause in women is unclear. Women ( = 162) aged 40-65 years completed a survey rating their knowledge, answered fact-based questions and reported their experiences of menopause. Their levels of, and beliefs on, the role physical activity on symptoms and menopause associated disease risk were also collected. Women reported their confidence in their current knowledge level at 67% reflecting 37% higher rating than an estimate of their knowledge 10 years ago. Their factual knowledge score was 56%. Knowledge was primarily gained through friends and family and almost half (46%) had not spoken to a healthcare professional. Frustration was expressed with lack of knowledge and support of healthcare and others. Women using HRT (44%) had mixed attitudes towards its role. A high proportion were active and felt that physical activity can help manage symptoms and impact long-term health consequences of menopause. Menopause education strategies for women, healthcare professionals and others need to be improved. Lack of education may be causing women to struggle and feel negatively towards this life stage. Physical activity was viewed positively for the symptoms and a treatment during menopause and long-term health.
Topics: Humans; Female; Middle Aged; Health Knowledge, Attitudes, Practice; Menopause; Adult; Aged; Exercise; Surveys and Questionnaires; Motor Activity
PubMed: 38393976
DOI: 10.1177/20533691241235273 -
BMC Women's Health Oct 2023Resistance training (RT) is effective in counteracting the age- and menopause-related loss of muscle mass (MM) and strength in middle-aged women (40-60 years). Research... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Resistance training (RT) is effective in counteracting the age- and menopause-related loss of muscle mass (MM) and strength in middle-aged women (40-60 years). Research on RT with free weights is limited in pre- and post-menopausal women. Based on this, a 20-week training intervention was conducted with this population to investigate the effects of systematic RT with free weights on strength capacity and body composition.
METHOD
Forty-one healthy women (52.0 ± 3.6 years) participated in this study. After 10-week control phase (no RT, T0-T1) followed by a 10-week intervention phase (T1-T2) with RT twice a week and 6-8 sets of each muscle per week. Subjects were randomly assigned to a low-intensity (50% 1-RM) or moderate-intensity (75% 1-RM) RT group and divided into pre-menopausal and post-menopausal according to their hormone profile. Fat-free mass (FFM), MM, fat mass (FM), muscle thickness (Vastus lateralis (VL), Rectus femoris (RF), Triceps brachii (TB)), grip strength, 1-RM squat and bench press were assessed before and after each phase. Statistical analysis was performed using a linear mixed model to account for fixed (time and group) and random (individual) effects.
RESULTS
A total of 31 women successfully completed the study. No injuries occurred during the intervention. Significant increases in 1-RM squat and bench press were observed in all groups. No interaction effect was observed for the strength parameters. In pre-menopausal women, FFM, MM and RF muscle thickness increased significantly, while VL showed a trend. These effects were not present in post-menopausal women regardless of RT intensity.
CONCLUSION
RT with free weight is safe and effective for middle-aged women to increase 1-RM. Hypertrophy effects were found exclusively in pre-menopausal women. To achieve hypertrophy and/or body composition changes in post-menopausal women, larger training volumes (> 6-8 sets/muscle per week) are likely required.
Topics: Middle Aged; Humans; Female; Muscle Strength; Resistance Training; Muscle, Skeletal; Body Composition; Menopause; Hypertrophy
PubMed: 37803287
DOI: 10.1186/s12905-023-02671-y -
International Journal of Molecular... Mar 2024Menopause is a physiological phase of life of aging women, and more than 1 billion women worldwide will be in menopause by 2025. The processes of global senescence... (Review)
Review
Menopause is a physiological phase of life of aging women, and more than 1 billion women worldwide will be in menopause by 2025. The processes of global senescence parallel stages of reproductive aging and occur alongside aging-related changes in the body. Alterations in the endocrine pathways accompany and often predate the physiologic changes of aging, and interactions of these processes are increasingly being recognized as contributory to the progression of senescence. Our goal for this review is to examine, in aging women, the complex interplay between the endocrinology of menopause transition and post-menopause, and the metabolic transition, the hallmark being an increasing tendency towards central adiposity that begins in tandem with reproductive aging and is often exacerbated post menopause. For the purpose of this review, our choice of the terms 'female' and 'woman' refer to genetic females.
Topics: Female; Humans; Adiposity; Aging; Menopause; Postmenopause; Reproduction; Obesity
PubMed: 38474226
DOI: 10.3390/ijms25052972 -
Nutrients Feb 2024The causes of vasomotor symptoms, including hot flashes, are not fully understood, may be related to molecular factors, and have a polygenic architecture. Nutrients and... (Review)
Review
The causes of vasomotor symptoms, including hot flashes, are not fully understood, may be related to molecular factors, and have a polygenic architecture. Nutrients and bioactive molecules supplied to the body with food are metabolized using various enzymatic pathways. They can induce molecular cell signaling pathways and, consequently, activate effector proteins that modulate processes related to hot flashes in menopausal women. In this review, we analyzed the literature data from the last 5 years, especially regarding genome-wide association study (GWAS) analysis, and selected molecular factors and cell signaling pathways that may potentially be related to hot flashes in women. These are the kisspeptin-GnRH pathway, adipocyte-derived hormones, aryl hydrocarbon receptor signaling, catechol estrogens and estrogen sulfotransferase, inflammatory and oxidative stress biomarkers, and glucose availability. Then, single compounds or groups of food ingredients were selected that, according to experimental data, influence the course of the discussed molecular pathways and thus can be considered as potential natural therapeutic agents to effectively reduce the troublesome symptoms of menopause in women.
Topics: Female; Humans; Hot Flashes; Genome-Wide Association Study; Menopause; Hormones; Nutrients
PubMed: 38474783
DOI: 10.3390/nu16050655 -
Frontiers in Endocrinology 2023The metabolic characteristics of premature ovarian insufficiency (POI), a reproductive endocrine disease characterized by abnormal sex hormone metabolism and follicle...
BACKGROUND
The metabolic characteristics of premature ovarian insufficiency (POI), a reproductive endocrine disease characterized by abnormal sex hormone metabolism and follicle depletion, remain unclear. Metabolomics is a powerful tool for exploring disease phenotypes and biomarkers. This study aims to identify metabolic markers and construct diagnostic models, and elucidate the underlying pathological mechanisms for POI.
METHODS
Non-targeted metabolomics was utilized to characterize the plasma metabolic profile of 40 patients. The metabolic markers were identified through bioinformatics and machine learning, and constructed an optimal diagnostic model by classified multi-model analysis. Enzyme-linked immunosorbent assay (ELISA) was used to verify antioxidant indexes, mitochondrial enzyme complexes, and ATP levels. Finally, integrated transcriptomics and metabolomics were used to reveal the dysregulated pathways and molecular regulatory mechanisms of POI.
RESULTS
The study identified eight metabolic markers significantly correlated with ovarian reserve function. The XGBoost diagnostic model was developed based on six machine learning models, demonstrating its robust diagnostic performance and clinical applicability through the evaluation of receiver operating characteristic (ROC) curve, decision curve analysis (DCA), calibration curve, and precise recall (PR) curve. Multi-omics analysis showed that mitochondrial respiratory chain electron carrier (CoQ10) and enzyme complex subunits were down-regulated in POI. ELISA validation revealed an elevation in oxidative stress markers and a reduction in the activities of antioxidant enzymes, CoQ10, and mitochondrial enzyme complexes in POI.
CONCLUSION
Our findings highlight that mitochondrial dysfunction and energy metabolism disorders are closely related to the pathogenesis of POI. The identification of metabolic markers and predictive models holds significant implications for the diagnosis, treatment, and monitoring of POI.
Topics: Female; Humans; Antioxidants; Primary Ovarian Insufficiency; Menopause, Premature; Biomarkers; Gene Expression Profiling
PubMed: 38179298
DOI: 10.3389/fendo.2023.1280248