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Sleep Medicine May 2021Sleep quality typically decreases after menopause, but the underlying mechanisms are poorly understood. Concentrations of melatonin are lower and its secretion profiles...
BACKGROUND
Sleep quality typically decreases after menopause, but the underlying mechanisms are poorly understood. Concentrations of melatonin are lower and its secretion profiles different before and after menopause. However, whether and how melatonin and sleep architecture are associated in women of different reproductive states have not been examined to date.
METHODS
Overnight serum melatonin samples were taken from 17 perimenopausal and 18 postmenopausal healthy women. Sleep quality was measured with all-night polysomnography recordings.
RESULTS
Melatonin concentrations tended to be the lowest during NREM sleep, and were associated with higher odds of transitions from wake to NREM sleep. The curves of predicted overnight melatonin values from linear mixed models varied according to sleep phases (NREM, REM, Wake) in perimenopausal, but not in postmenopausal women. In perimenopause higher melatonin area under curve (AUC) correlated with higher slow-wave activity (p = 0.043), and higher minimum concentrations with shorter slow-wave sleep (SWS) latency (p = 0.029). In postmenopause higher mean and maximum melatonin concentrations and AUC correlated with lower SWS percentage (p = 0.044, p = 0.029, p = 0.032), and higher mean (p = 0.032), maximum (p = 0.032) and minimum (p = 0.037) concentrations with more awakenings from REM sleep. In the age- and BMI- adjusted regression models, the association between higher maximum (p = 0.046) melatonin concentration and lower SWS percentage remained.
CONCLUSIONS
The relationship between melatonin and sleep architecture differed in perimenopausal and postmenopausal women. After menopause, high melatonin concentrations were associated with worse sleep. Whether these different patterns are related to aging of the reproductive system, and to decrease in menopausal sleep quality, remains to be elucidated.
Topics: Female; Humans; Melatonin; Perimenopause; Polysomnography; Postmenopause; Sleep
PubMed: 33639482
DOI: 10.1016/j.sleep.2021.02.011 -
Maturitas Sep 2023In addition to a range of physiological and psychological symptoms, menopause causes a decrement to balance performance and risk of falls. This review aimed to determine... (Meta-Analysis)
Meta-Analysis Review
The comparative effect of exercise interventions on balance in perimenopausal and early postmenopausal women: A systematic review and network meta-analysis of randomised, controlled trials.
In addition to a range of physiological and psychological symptoms, menopause causes a decrement to balance performance and risk of falls. This review aimed to determine the effects of exercise interventions on balance in perimenopausal and early postmenopausal women. Web of Science, PubMed, CINAHL, SPORTDiscus and Cochrane Central Register of Controlled Trials databases were searched. Randomised, controlled trials of exercise interventions in perimenopausal or early postmenopausal populations with an average age of 65 years or younger reporting balance measures were included. Risk of bias was assessed using Cochrane RoB 2. A random effects model network meta-analysis was performed to assess the effect of exercise on balance. Standardised mean differences with 95 % confidence intervals were used as the measure of effect. Twenty-six studies were included after screening. Network meta-analyses were conducted for 5 balance variables. Whole-body vibration (standardised mean difference: 2.25, confidence interval: 0.08; 4.43), balance (standardised mean difference: 1.84, confidence interval: 0.15; 3.53), balance + nutrition (standardised mean difference: 3.81, confidence interval: 1.57; 6.05) and resistance (standardised mean difference: 1.43, confidence interval: 0.41; 2.46) exercise improved Berg balance scale performance. Resistance + aerobic + balance exercise improved one-leg stance (standardised mean difference: 0.80, confidence interval: 0.39; 1.22) and whole-body vibration improved anterior-posterior (standardised mean difference: -0.89, confidence interval: -1.48; -0.31), medio-lateral (standardised mean difference: -0.58, confidence interval: -1.15; -0.01) postural sway and falls indices (standardised mean difference: -0.75, confidence interval: -1.45; -0.04). Exercise improved all balance measures and should be considered as an adjunct therapy in perimenopausal and postmenopausal women. Whole-body vibration was most frequently the highest ranked intervention; resistance and balance training also improved balance.
Topics: Humans; Female; Aged; Network Meta-Analysis; Postmenopause; Perimenopause; Exercise; Exercise Therapy; Randomized Controlled Trials as Topic
PubMed: 37343343
DOI: 10.1016/j.maturitas.2023.107790 -
Current Psychiatry Reports Oct 2023To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and... (Review)
Review
PURPOSE OF REVIEW
To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and neural biomarkers are associated with cognitive problems and which interventions demonstrate efficacy at improving cognitive performance.
RECENT FINDINGS
Cognitive problems are common during perimenopause and have a significant impact on a substantial proportion of women. Evidence continues to indicate that verbal learning and verbal memory are the cognitive functions that are most negatively affected during perimenopause, and new research suggests that perimenopause may also be associated with deficits in processing speed, attention, and working memory. Recent research suggests that the cognitive profiles of women transitioning through perimenopause are heterogenous - with some showing strengths and others demonstrating weaknesses in particular cognitive domains. Depression, sleep problems, and vasomotor symptoms in perimenopause may be associated with cognitive difficulties. Recent neuroimaging studies are identifying changes in activity patterns within brain regions that correlate with cognitive performance in perimenopause, but future causal studies are needed to understand the neural mechanisms of cognitive problems during this time. Although clinical treatment studies for cognitive concerns have historically focused on postmenopause, some small trials in perimenopausal samples have been conducted recently but are frequently underpowered. Current guidelines from the North American Menopause Society do not support the use of hormone therapy at any age for cognitive problems. Animal research demonstrates that estradiol and levonorgestrel combined may alleviate working memory problems. Much progress has been made in understanding how perimenopause impacts cognition, and more research is needed to better identify who is at highest risk and how to meaningfully prevent and alleviate cognitive problems during this reproductive stage. Larger-scale randomized intervention trials specifically during perimenopause are urgently needed to address cognitive concerns in this population of women. More consistent reproductive staging, inclusion of covariates, and analyses examining perimenopause specifically would improve study quality and the ability to draw clear conclusions from this research.
Topics: Female; Humans; Perimenopause; Menopause; Postmenopause; Estradiol; Cognition
PubMed: 37755656
DOI: 10.1007/s11920-023-01447-3 -
The Journal of Clinical Endocrinology... Sep 2021Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful...
CONTEXT
Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD.
OBJECTIVE
We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test.
METHODS
Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing.
RESULTS
No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women.
CONCLUSION
Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions.
Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Depression; Dexamethasone; Estradiol; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Perimenopause; Pituitary-Adrenal System; Progesterone
PubMed: 34097071
DOI: 10.1210/clinem/dgab407 -
Obstetrics and Gynecology Clinics of... Sep 2011The impact of perimenopause on cognition seems to be characterized by an absence of improved scores rather than a decline. In the SWAN, the perimenopausal decrement in... (Review)
Review
The impact of perimenopause on cognition seems to be characterized by an absence of improved scores rather than a decline. In the SWAN, the perimenopausal decrement in cognitive performance was not accounted for; however, increases in anxiety and depressive symptoms had independent, unfavorable effects on performance. Estradiol has been found to protect against changes resulting from serotonin withdrawal and defend against changes from cholinergic depletion. There is support for the critical timing hypothesis--that estrogen benefits cognitive function when instituted early, but not later. The menopausal transition may affect cognitive function in older age owing to worsened cardiovascular risk factors.
Topics: Age Factors; Animals; Brain; Cardiovascular Diseases; Cognition Disorders; Estrogens; Female; Gonadal Steroid Hormones; Humans; Hydrocortisone; Models, Animal; Ovariectomy; Perimenopause; Primary Ovarian Insufficiency
PubMed: 21961718
DOI: 10.1016/j.ogc.2011.05.007 -
Journal of Affective Disorders Mar 2022Previous work implicates high pro-inflammatory biomarkers in mood disturbance and low brain-derived neurotrophic factor (BDNF) levels in major depression. However, in...
BACKGROUND
Previous work implicates high pro-inflammatory biomarkers in mood disturbance and low brain-derived neurotrophic factor (BDNF) levels in major depression. However, in hormonally-sensitive premenstrual dysphoric disorder (PMDD), BDNF levels are higher when mood is worse. Perimenopausal depression has not been studied to date. We evaluated whether BDNF and inflammatory cytokines predict mood symptoms across the menstrual cycle in hormonally-sensitive perimenopausal depression symptoms.
METHODS
Data from 49 time points derived from mid-to-late follicular phase [M/L-FP] and peri‑menstrual assessments of 14 perimenopausal women ages 38-52 with ovulatory menstrual cycles 24-35 days long across 1-2 cycles for mood symptoms, BDNF levels, cytokines, gonadal steroids. Depression was assessed with Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI); irritability with Kellner Symptom Questionnaire Anger-Hostility subscale (SQ); overall psychological distress with Profile of Mood States (POMS). Mixed models were run on dependent measures of MADRS (primary endpoint) and other mood outcomes (BDI, POMS, SQ) with independent variables of interest (each biomarker, cycle phase), controlling for cycle number and participant.
RESULTS
After FDR adjustment, BDNF levels showed consistent significant positive relationships to MADRS (β=0.00053; p = 0.0028), POMS (β=0.00153; p = 0.0394), SQ (β=0.00053; p = 0.0067), and BDI (β=0.00039; p = 0.0231). Cycle phase did not affect this relationship. No other biomarker consistently predicted affective symptom severity.
LIMITATIONS
Small sample size and large number of comparisons.
CONCLUSION
In women with perimenopausal depression symptoms, BDNF is elevated in association with more severe mood symptomatology, resembling the pattern in hormonally-sensitive PMDD and suggesting a hormonally-sensitive mood disorder biomarker profile distinct from that of major depression.
Topics: Adult; Affect; Brain-Derived Neurotrophic Factor; Depression; Female; Follicular Phase; Humans; Middle Aged; Perimenopause; Premenstrual Dysphoric Disorder
PubMed: 34954335
DOI: 10.1016/j.jad.2021.12.092 -
Menopause (New York, N.Y.) Jul 2017Abnormalities in autonomic function are posited to play a pathophysiologic role in menopausal hot flashes. We examined relationships between resting cardiac autonomic... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Abnormalities in autonomic function are posited to play a pathophysiologic role in menopausal hot flashes. We examined relationships between resting cardiac autonomic activity and hot flashes in perimenopausal and postmenopausal women.
METHODS
Autonomic function was assessed at baseline and 12 weeks among perimenopausal and postmenopausal women (n = 121, mean age 53 years) in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, was measured with impedance cardiography. Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, was measured with electrocardiography. Participants self-reported hot flash frequency and severity in 7-day symptom diaries. Analysis of covariance models were used to relate autonomic function and hot flash frequency and severity at baseline, and to relate changes in autonomic function to changes in hot flash frequency and severity over 12 weeks, adjusting for age, body mass index, and intervention assignment.
RESULTS
PEP was not associated with hot flash frequency or severity at baseline or over 12 weeks (P > 0.05 for all). In contrast, there was a trend toward greater frequency of moderate-to-severe hot flashes with higher RSA at baseline (β = 0.43, P = 0.06), and a positive association between change in RSA and change in frequency of moderate-to-severe hot flashes over 12 weeks (β = 0.63, P = 0.04).
CONCLUSIONS
Among perimenopausal and postmenopausal women with hot flashes, variations in hot flash frequency and severity were not explained by variations in resting sympathetic activation. Greater parasympathetic activation was associated with more frequent moderate-to-severe hot flashes, which may reflect increased sensitivity to perceiving hot flashes.
Topics: Adult; Autonomic Nervous System; Electrocardiography; Female; Heart; Hot Flashes; Humans; Middle Aged; Perimenopause; Postmenopause; Rest; Severity of Illness Index; Single-Blind Method
PubMed: 28169914
DOI: 10.1097/GME.0000000000000843 -
Menopause (New York, N.Y.) Jun 2023Distressing sexual problems are a common complaint of menopausal women. In 2013, a Cochrane review assessed the effect of hormone therapy on sexual function in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Distressing sexual problems are a common complaint of menopausal women. In 2013, a Cochrane review assessed the effect of hormone therapy on sexual function in menopausal women; however, new evidence has since been published, which should be considered.
OBJECTIVE
This systematic review and meta-analysis aims to update the evidence synthesis on the effect of hormone therapy, compared with control, on sexual function in perimenopausal and postmenopausal women.
EVIDENCE REVIEW
Thirteen databases and clinical trial registries (Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Literatura Latino-Americana e do Caribe em Ciéncias da Saúde, Database of Abstracts of Reviews of Effects, ClinicalTrials.gov , International Clinical Trials Registry Platform, Iranian Registry of Clinical Trials, Chinese Clinical Trial Registry, ISRCTN) were searched from December 2012 to March 30, 2022. Backward reference searching on all retrieved full texts was also performed. Study quality was assessed using the Cochrane ROB.2 tool. Data were pooled in random-effect model meta-analyses, which included all studies identified in the present search and all studies previously included in the 2013 Cochrane review.
FINDINGS
Forty-seven randomized controlled trials (35,912 participants) were included in the systematic review, and 34 randomized controlled trials (15,079 participants) were included in the meta-analysis. The meta-analysis revealed that, in comparison to control, estrogen therapy (standardized mean difference [SMD], 0.16; 95% confidence interval [CI], 0.02 to 0.29; I2 = 59%; 2,925 participants, 16 studies), estrogen plus progestogen therapy (SMD, 0.11; 95% CI, -0.07 to 0.29; I2 = 65%; 2,432 participants, 7 studies), tibolone (SMD, 0.15; 95% CI, 0.02 to 0.28; I2 = 0%; 916 participants, 2 studies), and selective estrogen receptor modulators (SMD, 0.18; 95% CI, 0.06 to 0.30; I2 = 0%; 1,058 participants, 4 studies) may result in no effect to small benefit on sexual function composite score.
CONCLUSION AND RELEVANCE
Hormone therapy may slightly improve sexual functioning. This potential small benefit should be considered when discussing treatment options for other menopausal symptoms.
Topics: Female; Humans; Postmenopause; Perimenopause; Iran; Estrogens; Menopause
PubMed: 37159867
DOI: 10.1097/GME.0000000000002185 -
Scientific Reports Jun 2023This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg... (Randomized Controlled Trial)
Randomized Controlled Trial
This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg oral micronized progesterone@bedtime versus placebo for 3-months (m) after a 1-m untreated baseline during 2012/1-2017/4. We randomized untreated, non-depressed, screen- and baseline-eligible by VMS, perimenopausal women (with flow within 1-year), ages 35-58 (n = 189). Participants aged 50 (± SD = 4.6) were mostly White, educated, minimally overweight with 63% in late perimenopause; 93% participated remotely. The 1° outcome was 3rd-m VMS Score difference. Participants recorded VMS number and intensity (0-4 scale)/24 h on a VMS Calendar. Randomization required VMS (intensity 2-4/4) of sufficient frequency and/or ≥ 2/week night sweat awakenings. Baseline total VMS Score (SD) was 12.2 (11.3) without assignment difference. Third-m VMS Score did not differ by therapy (Rate Difference - 1.51). However, the 95% CI [- 3.97, 0.95] P = 0.222, did not exclude 3, a minimal clinically important difference. Women perceived progesterone caused decreased night sweats (P = 0.023) and improved sleep quality (P = 0.005); it decreased perimenopause-related life interference (P = 0.017) without increased depression. No serious adverse events occurred. Perimenopausal night sweats ± hot flushes are variable; this RCT was underpowered but could not exclude a minimal clinically important VMS benefit. Perceived night sweats and sleep quality significantly improved.
Topics: Female; Humans; Perimenopause; Progesterone; Sweat; Postmenopause; Hot Flashes; Canada
PubMed: 37277418
DOI: 10.1038/s41598-023-35826-w -
Journal of Nanobiotechnology Aug 2023The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous...
The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.
Topics: Mice; Animals; Nanogels; Depression; Reactive Oxygen Species; Exosomes; Perimenopause; Pituitary Adenylate Cyclase-Activating Polypeptide; Drug Carriers
PubMed: 37553718
DOI: 10.1186/s12951-023-02005-y