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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 -
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 -
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 -
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 -
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 -
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 -
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 -
The Cochrane Database of Systematic... Sep 2012Menopause can be a distressing and disruptive time for many women, with many experiencing hot flushes, night sweats, vaginal atrophy and dryness. Postmenopausal women... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Menopause can be a distressing and disruptive time for many women, with many experiencing hot flushes, night sweats, vaginal atrophy and dryness. Postmenopausal women are also at increased risk of osteoporosis. Interventions that decrease the severity and frequency of these menopausal symptoms are likely to improve a woman's well-being and quality of life. Hormone therapy has been shown to be effective in controlling the symptoms of menopause; however, many potentially serious adverse effects have been associated with this treatment. Evidence from experimental studies suggests that black cohosh may be a biologically plausible alternative treatment for menopause; even so, findings from studies investigating the clinical effectiveness of black cohosh have, to date, been inconsistent.
OBJECTIVES
To evaluate the clinical effectiveness and safety of black cohosh (Cimicifuga racemosa or Actaea racemosa) for treating menopausal symptoms in perimenopausal and postmenopausal women.
SEARCH METHODS
Relevant studies were identified through AARP Ageline, AMED, AMI, BioMed Central gateway, CAM on PubMed, CINAHL, CENTRAL, EMBASE, Health Source Nursing/Academic edition, International Pharmaceutical Abstracts, MEDLINE, Natural medicines comprehensive database, PsycINFO, TRIP database, clinical trial registers and the reference lists of included trials; up to March 2012. Content experts and manufacturers of black cohosh extracts were also contacted.
SELECTION CRITERIA
All randomised controlled trials comparing orally administered monopreparations of black cohosh to placebo or active medication in perimenopausal and postmenopausal women.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data and completed the 'Risk of bias' assessment. Study authors were contacted for missing information.
MAIN RESULTS
Sixteen randomised controlled trials, recruiting a total of 2027 perimenopausal or postmenopausal women, were identified. All studies used oral monopreparations of black cohosh at a median daily dose of 40 mg, for a mean duration of 23 weeks. Comparator interventions included placebo, hormone therapy, red clover and fluoxetine. Reported outcomes included vasomotor symptoms, vulvovaginal symptoms, menopausal symptom scores and adverse effects. There was no significant difference between black cohosh and placebo in the frequency of hot flushes (mean difference (MD) 0.07 flushes per day; 95% confidence interval (CI) -0.43 to 0.56 flushes per day; P=0.79; 393 women; three trials; moderate heterogeneity: I(2) = 47%) or in menopausal symptom scores (standardised mean difference (SMD) -0.10; 95% CI -0.32 to 0.11; P = 0.34; 357 women; four trials; low heterogeneity: I(2) = 21%). Compared to black cohosh, hormone therapy significantly reduced daily hot flush frequency (three trials; data not pooled) and menopausal symptom scores (SMD 0.32; 95% CI 0.13 to 0.51; P=0.0009; 468 women; five trials; substantial heterogeneity: I(2) = 69%). These findings should be interpreted with caution given the heterogeneity between studies. Comparisons of the effectiveness of black cohosh and other interventions were either inconclusive (because of considerable heterogeneity or an insufficient number of studies) or not statistically significant. Similarly, evidence on the safety of black cohosh was inconclusive, owing to poor reporting. There were insufficient data to pool results for health-related quality of life, sexuality, bone health, vulvovaginal atrophic symptoms and night sweats. No trials reported cost-effectiveness data. The quality of included trials was generally unclear, owing to inadequate reporting.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to support the use of black cohosh for menopausal symptoms. However, there is adequate justification for conducting further studies in this area. The uncertain quality of identified trials highlights the need for improved reporting of study methods, particularly with regards to allocation concealment and the handling of incomplete outcome data. The effect of black cohosh on other important outcomes, such as health-related quality of life, sexuality, bone health, night sweats and cost-effectiveness also warrants further investigation.
Topics: Cimicifuga; Dehydration; Female; Hot Flashes; Humans; Middle Aged; Perimenopause; Phytotherapy; Postmenopause; Randomized Controlled Trials as Topic; Sweating; Trifolium; Vaginal Diseases
PubMed: 22972105
DOI: 10.1002/14651858.CD007244.pub2 -
Obstetrics and Gynecology Clinics of... Dec 2018This article reviews the role of endogenous estrogen in neural and cognitive processing, followed by an examination of longitudinal cognitive data captured in various... (Review)
Review
This article reviews the role of endogenous estrogen in neural and cognitive processing, followed by an examination of longitudinal cognitive data captured in various stages of the menopausal transition. The remaining text reviews the contradictory results from major hormone therapy trials to date, evidence for the "timing hypothesis," and closes with recommendations for future research and for practicing clinicians.
Topics: Aging; Cognition; Cognition Disorders; Estrogen Replacement Therapy; Estrogens; Evidence-Based Medicine; Female; Humans; Menopause; Neuroprotection; Perimenopause; Reproductive Health; Women's Health
PubMed: 30401555
DOI: 10.1016/j.ogc.2018.07.011 -
Obstetrics and Gynecology Clinics of... Dec 2018Vulnerability to depression is increased across the menopause transition and in the early years after the final menstrual period. Clinicians should systematically screen... (Review)
Review
Vulnerability to depression is increased across the menopause transition and in the early years after the final menstrual period. Clinicians should systematically screen women in this age group; if depressive symptoms or disorder are present, treatment of depression should be initiated. Potential treatments include antidepressants for moderate to severe symptoms, psychotherapy to target psychological and interpersonal factors, and hormone therapy for women with first-onset major depressive disorder or elevated depressive symptoms and at low risk for adverse effects. Behavioral interventions can improve physical activity and sleep patterns.
Topics: Antidepressive Agents; Cognitive Behavioral Therapy; Depression; Female; Gene-Environment Interaction; Gonadal Steroid Hormones; Hormone Replacement Therapy; Humans; Longitudinal Studies; Perimenopause; Psychotherapy
PubMed: 30401549
DOI: 10.1016/j.ogc.2018.07.007