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The Journal of Prevention of... 2018Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD... (Review)
Review
Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Commonly characterized as ending in reproductive senescence, many symptoms of MT are neurological, including disruption of estrogen-regulated systems such as thermoregulation, sleep, and circadian rhythms, as well as depression and impairment in multiple cognitive domains. Preclinical studies have shown that, during MT, the estrogen network uncouples from the brain bioenergetic system. The resulting hypometabolic state could serve as the substrate for neurological dysfunction. Indeed, translational brain imaging studies demonstrate that 40-60 year-old perimenopausal and postmenopausal women exhibit an AD-endophenotype characterized by decreased metabolic activity and increased brain amyloid-beta deposition as compared to premenopausal women and to age-matched men. This review discusses the MT as a window of opportunity for therapeutic interventions to compensate for brain bioenergetic crisis and combat the subsequent increased risk for AD in women.
Topics: Alzheimer Disease; Brain; Female; Hormone Replacement Therapy; Humans; Menopause; Risk Factors
PubMed: 30298180
DOI: 10.14283/jpad.2018.34 -
Obesity (Silver Spring, Md.) Jan 2022Every 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... (Review)
Review
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.
Topics: Body Composition; Cardiovascular Diseases; Energy Metabolism; Female; Humans; Menopause; Perimenopause
PubMed: 34932890
DOI: 10.1002/oby.23289 -
Nature Reviews. Endocrinology Jul 2015Perimenopause is a midlife transition state experienced by women that occurs in the context of a fully functioning neurological system and results in reproductive... (Review)
Review
Perimenopause is a midlife transition state experienced by women that occurs in the context of a fully functioning neurological system and results in reproductive senescence. Although primarily viewed as a reproductive transition, the symptoms of perimenopause are largely neurological in nature. Neurological symptoms that emerge during perimenopause are indicative of disruption in multiple estrogen-regulated systems (including thermoregulation, sleep, circadian rhythms and sensory processing) and affect multiple domains of cognitive function. Estrogen is a master regulator that functions through a network of estrogen receptors to ensure that the brain effectively responds at rapid, intermediate and long timescales to regulate energy metabolism in the brain via coordinated signalling and transcriptional pathways. The estrogen receptor network becomes uncoupled from the bioenergetic system during the perimenopausal transition and, as a corollary, a hypometabolic state associated with neurological dysfunction can develop. For some women, this hypometabolic state might increase the risk of developing neurodegenerative diseases later in life. The perimenopausal transition might also represent a window of opportunity to prevent age-related neurological diseases. This Review considers the importance of neurological symptoms in perimenopause in the context of their relationship to the network of estrogen receptors that control metabolism in the brain.
Topics: Affect; Anxiety; Arousal; Attention; Brain; Cognition; Eating; Estrogens; Executive Function; Female; Humans; Learning; Memory; Perimenopause; Receptors, Estrogen
PubMed: 26007613
DOI: 10.1038/nrendo.2015.82 -
Nutrients Dec 2023Menopause is associated with an increased prevalence of obesity, metabolic syndrome, cardiovascular diseases, and osteoporosis. These diseases and unfavorable laboratory... (Review)
Review
Menopause is associated with an increased prevalence of obesity, metabolic syndrome, cardiovascular diseases, and osteoporosis. These diseases and unfavorable laboratory values, which are characteristic of this period in women, can be significantly improved by eliminating and reducing dietary risk factors. Changing dietary habits during perimenopause is most effectively achieved through nutrition counseling and intervention. To reduce the risk factors of all these diseases, and in the case of an already existing disease, dietary therapy led by a dietitian should be an integral part of the treatment. The following review summarizes the recommendations for a balanced diet and fluid intake, the dietary prevention of cardiovascular diseases, the role of sleep, and the key preventive nutrients in menopause, such as vitamin D, calcium, vitamin C, B vitamins, and protein intake. In summary, during the period of perimenopause and menopause, many lifestyle factors can reduce the risk of developing all the diseases (cardiovascular disease, insulin resistance, type 2 diabetes mellitus, osteoporosis, and tumors) and symptoms characteristic of this period.
Topics: Female; Humans; Perimenopause; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Menopause; Vitamins; Osteoporosis
PubMed: 38201856
DOI: 10.3390/nu16010027 -
Clinical Obstetrics and Gynecology Sep 2018Perimenopause, or the menopausal transition, represents a period of time during which newly arising symptoms can present complex management decisions for providers. Many... (Review)
Review
Perimenopause, or the menopausal transition, represents a period of time during which newly arising symptoms can present complex management decisions for providers. Many women present to care with complaints of hot flashes, vaginal and sexual changes, altered mood and sleep, and changing bleeding patterns. The effect of these symptoms on quality of life, even before a woman enters menopause, can be significant. The appropriate evaluation and evidence-based management of women in this transition is reviewed in this article. Two case vignettes are used to highlight certain evaluation and treatment challenges.
Topics: Affect; Androgens; Anti-Mullerian Hormone; Biomarkers; Evidence-Based Practice; Female; Follicle Stimulating Hormone; Hot Flashes; Humans; Menstruation Disturbances; Perimenopause; Sexual Dysfunction, Physiological; Sleep Initiation and Maintenance Disorders
PubMed: 29952797
DOI: 10.1097/GRF.0000000000000389 -
Clinical Cancer Research : An Official... Mar 2022Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase III MONALEESA-7... (Randomized Controlled Trial)
Randomized Controlled Trial
Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial.
PURPOSE
Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase III MONALEESA-7 trial of pre-/perimenopausal patients with hormone receptor (HR)-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). The median OS was not reached in the ribociclib arm in the protocol-specified final analysis; we hence performed an exploratory OS and additional outcomes analysis with an extended follow-up (median, 53.5 months).
PATIENTS AND METHODS
Patients were randomized to receive ET [goserelin plus nonsteroidal aromatase inhibitor (NSAI) or tamoxifen] with ribociclib or placebo. OS was evaluated with a stratified Cox proportional hazard model and summarized with Kaplan-Meier methods.
RESULTS
The intent-to-treat population included 672 patients. Median OS was 58.7 months with ribociclib versus 48.0 months with placebo [hazard ratio = 0.76; 95% confidence interval (CI), 0.61-0.96]. Kaplan-Meier estimated OS at 48 months was 60% and 50% with ribociclib and placebo, respectively. Subgroup analyses were generally consistent with the OS benefit, including patients who received NSAI and patients aged less than 40 years. Subsequent antineoplastic therapies following discontinuation were balanced between the ribociclib (77%) and placebo (78%) groups. Use of cyclin-dependent kinase 4/6 inhibitors after discontinuation was higher with placebo (26%) versus ribociclib (13%). Time to first chemotherapy was significantly delayed with ribociclib versus placebo. No drug-drug interactions were observed between ribociclib and either NSAI.
CONCLUSIONS
Ribociclib plus ET continued to show significantly longer OS than ET alone in pre-/perimenopausal patients, including patients aged less than 40 years, with HR+/HER2- ABC with 53.5 months of median follow-up (ClinicalTrials.gov, NCT02278120).
Topics: Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Perimenopause; Purines; Receptor, ErbB-2; Receptors, Estrogen
PubMed: 34965945
DOI: 10.1158/1078-0432.CCR-21-3032 -
Menopause (New York, N.Y.) Feb 2020Uterine fibroids (UFs) are benign tumors that arise from a single genetically altered mesenchymal stem cell under the influence of gonadal hormones. UFs are the most... (Review)
Review
Uterine fibroids (UFs) are benign tumors that arise from a single genetically altered mesenchymal stem cell under the influence of gonadal hormones. UFs are the most common benign gynecologic tumors in premenopausal women worldwide. It is estimated that nearly 70% to 80% of women will develop UFs at some point during their lifetime. UFs often present with abnormal uterine bleeding (AUB), pelvic fullness, and may have deleterious effects on fertility. The natural regression of UFs begins in menopause. This is, however, a generality as this pathology may still be present in this age group. Many clinicians are concerned about hormone therapy (HT) because of UFs regrowth; nevertheless, research of this subject remains inconclusive. If UFs are present in perimenopause or menopause, they typically manifest as AUB, which represents up to 70% of all gynecological consultations in perimenopausal and postmenopausal women. As AUB is a broad symptom and may not be specific to UFs, a thorough evaluation is required for correct diagnosis and proper treatment accordingly. Understanding the unique characteristics of the available treatment modalities is crucial in deciding the appropriate treatment approach. Decision on treatment modality should be made based on selection of the least morbidity and lowest risk for each patient. Multiple modalities are available; however, surgery remains the method of choice, with the best cure rates. Various attempts to create an inexpensive, safe, and effective drug for the treatments of UFs are still in the early stages of the clinical trials with some showing great promise. Treatment options include tibolone, aromatase inhibitors, selective estrogen receptor modulators, uterine artery embolization, and selective progesterone receptor modulators.
Topics: Female; Hormone Antagonists; Humans; Leiomyoma; Menopause; Middle Aged; Perimenopause; Uterine Artery Embolization; Uterine Neoplasms
PubMed: 31834160
DOI: 10.1097/GME.0000000000001438 -
The Cochrane Database of Systematic... Jan 2017BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment. SEARCH METHODS: We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews. SELECTION CRITERIA: We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods. MAIN RESULTS: We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use: from 2 per 1000 to between 3 and 7 per 1000), venous thromboembolism (after 1 year's use: from 2 per 1000 to between 4 and 11 per 1000), stroke (after 3 years' use: from 6 per 1000 to between 6 and 12 per 1000), breast cancer (after 5.6 years' use: from 19 per 1000 to between 20 and 30 per 1000), gallbladder disease (after 5.6 years' use: from 27 per 1000 to between 38 and 60 per 1000) and death from lung cancer (after 5.6 years' use plus 2.4 years' additional follow-up: from 5 per 1000 to between 6 and 13 per 1000).Oestrogen-only HT increased the risk of venous thromboembolism (after 1 to 2 years' use: from 2 per 1000 to 2 to 10 per 1000; after 7 years' use: from 16 per 1000 to 16 to 28 per 1000), stroke (after 7 years' use: from 24 per 1000 to between 25 and 40 per 1000) and gallbladder disease (after 7 years' use: from 27 per 1000 to between 38 and 60 per 1000) but reduced the risk of breast cancer (after 7 years' use: from 25 per 1000 to between 15 and 25 per 1000) and clinical fracture (after 7 years' use: from 141 per 1000 to between 92 and 113 per 1000) and did not increase the risk of coronary events at any follow-up time.Women over 65 years of age who were relatively healthy and taking continuous combined HT showed an increase in the incidence of dementia (after 4 years' use: from 9 per 1000 to 11 to 30 per 1000). Among women with cardiovascular disease, use of combined continuous HT significantly increased the risk of venous thromboembolism (at 1 year's use: from 3 per 1000 to between 3 and 29 per 1000). Women taking HT had a significantly decreased incidence of fracture with long-term use.Risk of fracture was the only outcome for which strong evidence showed clinical benefit derived from HT (after 5.6 years' use of combined HT: from 111 per 1000 to between 79 and 96 per 1000; after 7.1 years' use of oestrogen-only HT: from 141 per 1000 to between 92 and 113 per 1000). Researchers found no strong evidence that HT has a clinically meaningful impact on the incidence of colorectal cancer.One trial analysed subgroups of 2839 relatively healthy women 50 to 59 years of age who were taking combined continuous HT and 1637 who were taking oestrogen-only HT versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT: Their absolute risk remained low, at less than 1/500. However, other differences in risk cannot be excluded, as this study was not designed to have the power to detect differences between groups of women within 10 years of menopause.For most studies, risk of bias was low in most domains. The overall quality of evidence for the main comparisons was moderate. The main limitation in the quality of evidence was that only about 30% of women were 50 to 59 years old at baseline, which is the age at which women are most likely to consider HT for vasomotor symptoms. AUTHORS' CONCLUSIONS: Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT, provided they do not have specific contraindications. HT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer (such as breast cancer, in women with a uterus). The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented.HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for prevention of deterioration of cognitive function in postmenopausal women. Although HT is considered effective for the prevention of postmenopausal osteoporosis, it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable. Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women and in postmenopausal women younger than 50 years of age.
Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Estrogen Replacement Therapy; Estrogens; Female; Hot Flashes; Humans; Middle Aged; Neoplasms; Perimenopause; Postmenopause; Progesterone; Randomized Controlled Trials as Topic; Venous Thromboembolism
PubMed: 28093732
DOI: 10.1002/14651858.CD004143.pub5 -
Journal of Women's Health (2002) Apr 2016The menopausal transition, or perimenopause, is associated with profound reproductive and hormonal changes. These changes have been well chronicled and matched with... (Review)
Review
The menopausal transition, or perimenopause, is associated with profound reproductive and hormonal changes. These changes have been well chronicled and matched with concomitant symptoms. The pattern of appearance of menopausal symptoms and their natural history have become increasingly clear thanks to the conduct of several long-term, longitudinal cohort studies that have examined many aspects of women's biology and psychology through this time of life. Menopausal symptoms are highly prevalent; they are sufficiently bothersome to drive almost 90% of women to seek out their healthcare provider for advice on how to cope. (1) The classic symptom of menopause is the hot flash, which is experienced by most women, and is moderately to severely problematic for about 1/3 of women. While most women will have an experience of hot flashes limited to just a year or two, others will experience them for a decade or more, and a small proportion of women will never be free of them. Poor sleep becomes more common in perimenopausal women not only in association with the menopausal transition but also in relation to aging. Depressed mood and increased anxiety also increase during the transition, with an abrupt rise in prevalence as women approach the later stages of the menopausal transition and have longer bouts of amenorrhea. These common symptoms often interact with one another such that depressed women tend to experience worse hot flashes along with worse sleep. As women enter the latter stages of the transition, vaginal dryness and dyspareunia also become more likely, affecting about 1/3 of the population. Unlike hot flashes, mood issues, and sleep, vaginal symptoms will not go away without treatment. Clinical approaches to these problems often involve hormone therapy, which can be safely given to most perimenopausal women on a short-term basis. Therapeutic strategies that are nonhormonal and behavioral can also be deployed.
Topics: Anxiety; Anxiety Disorders; Depression; Female; Hot Flashes; Humans; Irritable Mood; Perimenopause; Quality of Life; Sleep; Sleep Wake Disorders; Women's Health
PubMed: 26653408
DOI: 10.1089/jwh.2015.5556 -
Canadian Journal of Psychiatry. Revue... Sep 2016The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the... (Meta-Analysis)
Meta-Analysis Review
Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly.
BACKGROUND
The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.
METHODS
Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. This section on "Special Populations" is the sixth of six guidelines articles.
RESULTS
Recent studies inform the treatment of MDD in children and adolescents, pregnant and breastfeeding women, women in perimenopause or menopause, and the elderly. Evidence for efficacy of treatments in these populations is more limited than for the general adult population, however, and risks of treatment in these groups are often poorly studied and reported.
CONCLUSIONS
Despite the limited evidence base, extant data and clinical experience suggest that each of these special populations can benefit from the systematic application of treatment guidelines for treatment of MDD.
Topics: Adolescent Psychiatry; Adult; Aged; Canada; Child; Child Psychiatry; Depressive Disorder, Major; Evidence-Based Medicine; Female; Geriatric Psychiatry; Humans; Perimenopause; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications
PubMed: 27486149
DOI: 10.1177/0706743716659276