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Journal of the National Cancer Institute Jan 2022
Topics: Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Perimenopause; Tamoxifen
PubMed: 34396390
DOI: 10.1093/jnci/djab153 -
The Journal of Steroid Biochemistry and... Jul 2014The neuroendocrinology of menopause is reviewed from a comparative perspective, with emphasis on laboratory rodent models. These changes are compared by the 2011 STRAW... (Comparative Study)
Comparative Study Review
The neuroendocrinology of menopause is reviewed from a comparative perspective, with emphasis on laboratory rodent models. These changes are compared by the 2011 STRAW criteria (Stages of Reproductive Aging Workshop). Ovarian cell loss begins prenatally in all mammals studied, with exponential depletion of primary follicles and oocytes in association with loss of fecundity by midlife. Rodents and humans also share progressively increasing irregularity in ovulatory cycles and increasing fetal aneuploidy as oocyte depletion become imminent. Hypothalamic impairments of the estrogen-induced surge of pituitary gonadotrophins (luteinizing hormone, LH; follicle stimulating hormone, FSH) are prominent in middle-aged rodents, but sporadic in peri-menopausal women. In aging rodents, hypothalamic impairments of the LH surge have been experimentally associated with prolonged phases of sustained estradiol (E2) and very low progesterone (P4) ('unopposed estradiol'). Although peri-menopausal women also show hyper-estrogenic cycles, there is no indication for irreversible hypothalamic desensitization by E2. Ongoing cognitive assessments in clinical trials of estrogen therapy with and without P4 or other progestins may further inform about possible persisting effects of unopposed estrogens.This article is part of a Special Issue entitled 'Menopause'.
Topics: Adolescent; Adrenal Glands; Adult; Aging; Androgens; Animals; Child; Congenital Abnormalities; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hypothalamus; Luteinizing Hormone; Menopause; Middle Aged; Oocytes; Ovarian Follicle; Ovary; Perimenopause; Progesterone
PubMed: 23583565
DOI: 10.1016/j.jsbmb.2013.03.010 -
Neurobiology of Aging Feb 2019Perimenopause marks initiation of female reproductive senescence. Age of onset is only 47% heritable suggesting that additional factors other than inheritance regulate...
Perimenopause marks initiation of female reproductive senescence. Age of onset is only 47% heritable suggesting that additional factors other than inheritance regulate this endocrine aging transition. To elucidate these factors, we characterized transcriptional and epigenomic changes across endocrine aging using a rat model that recapitulates characteristics of the human perimenopause. RNA-seq analysis revealed that hypothalamic aging precedes onset of perimenopause. In the hypothalamus, global DNA methylation declined with both age and reproductive senescence. Genome-wide epigentic analysis revealed changes in DNA methylation in genes required for hormone signaling, glutamate signaling, and melatonin and circadian pathways. Specific epignetic changes in these signaling pathways provide insight into the origin of perimenopause-associated neurological symptoms such as insomnia. Treatment with 5-aza-2'-deoxycytidine, a DNA-methyltransferase-1 inhibitor, accelerated transition to reproductive senescence/ whereas supplementation with methionine, a S-adenosylmethionine precursor, delayed onset of perimenopause and endocrine aging. Collectively, these data provide evidence for a critical period of female neuroendocrine aging in brain that precedes ovarian failure and that DNA methylation regulates the transition duration of perimenopause to menopause.
Topics: Aging; Animals; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Decitabine; Disease Models, Animal; Enzyme Inhibitors; Epigenomics; Female; Genome-Wide Association Study; Hypothalamus; Menopause; Methionine; Neurosecretory Systems; Perimenopause; Rats, Sprague-Dawley; Reproduction; Signal Transduction; Transcription, Genetic
PubMed: 30497015
DOI: 10.1016/j.neurobiolaging.2018.09.029 -
Menopause (New York, N.Y.) Sep 2022Expanding access to legal cannabis has dovetailed with increased interest in medical cannabis (MC) use; however, there is a paucity of research examining MC use to...
OBJECTIVE
Expanding access to legal cannabis has dovetailed with increased interest in medical cannabis (MC) use; however, there is a paucity of research examining MC use to alleviate menopause-related symptoms. This survey study assessed patterns of MC use in perimenopausal and postmenopausal individuals.
METHODS
Participants (perimenopausal, n = 131; postmenopausal, n = 127) completed assessments of menopause-related symptomatology and cannabis use, including modes of use, type of use, and menopause-related symptoms addressed by MC use.
RESULTS
Most participants reported current cannabis use (86.1%) and endorsed using MC for menopause-related symptoms (78.7%). The most common modes of use were smoking (84.3%) and edibles (78.3%), and the top menopause-related symptoms for MC use were sleep disturbance (67.4%) and mood/anxiety (46.1%). Relative to postmenopausal participants, perimenopausal participants reported significantly worse menopause-related symptomatology on the vasomotor and psychosocial subscales of the Menopause-Specific Quality of Life Questionnaire ( P s ≤ 0.04), including greater burden of anxiety ( P = 0.01) and hot flash ( P = 0.04) symptoms. In addition, perimenopausal participants reported higher incidence of depression ( P = 0.03) and anxiety diagnoses ( P < 0.01), as well as increased use of MC to treat menopause-related mood/anxiety symptoms relative to postmenopausal participants ( P = 0.01).
CONCLUSIONS
Results suggest that many individuals are currently using MC as an adjunctive treatment for menopause-related symptoms, particularly sleep disturbance and mood/anxiety. Future research should examine the impact of different MC use characteristics (e.g., cannabinoid profiles) on the efficacy of MC use for menopause-related symptoms. Increased severity and prevalence of mood and anxiety symptoms in perimenopausal participants suggest promising targets for clinical trials of cannabinoid-based therapies.
Topics: Cannabinoids; Female; Hot Flashes; Humans; Medical Marijuana; Perimenopause; Postmenopause; Quality of Life; Surveys and Questionnaires
PubMed: 35917529
DOI: 10.1097/GME.0000000000002018 -
Psychological Medicine Jul 2022Women show a heightened risk for psychosis in midlife that is not observed in men. The menopausal transition (i.e. perimenopause) and accompanying changes in ovarian... (Review)
Review
Women show a heightened risk for psychosis in midlife that is not observed in men. The menopausal transition (i.e. perimenopause) and accompanying changes in ovarian hormones are theorized to account for this midlife increase in risk. This narrative review aims to empirically examine these theories by reviewing studies of midlife and perimenopausal psychosis risk in women and potential ovarian hormone mechanisms of effects. Clinical and pre-clinical studies examining the effects of midlife age, menopausal stage, and ovarian hormones across adulthood on psychosis risk were identified. Synthesis of this body of work revealed that the peak ages of midlife psychosis risk in women overlap with the age range of key menopausal stages (especially the perimenopausal transition), although studies directly assessing menopausal stage are lacking. Studies examining ovarian hormone effects have almost exclusively focused on earlier developmental stages and events (e.g. pregnancy, the menstrual cycle) and show increases in psychotic symptoms in women and female rats during periods of lower estradiol levels. Estrogen treatment also tends to enhance the effects of neuroleptics in females across species at various reproductive phases. Initial data are promising in suggesting a role for menopausal stage and ovarian hormones in psychosis risk. However, critical gaps in our knowledge base remain, as there is a tendency to rely on indirect and proxy measures of menopausal status and hormones. Opportunities for future research are discussed with the goal of increasing research in this critical area of women's health.
Topics: Animals; Female; Hormones; Humans; Menopause; Menstrual Cycle; Perimenopause; Psychotic Disorders; Rats
PubMed: 35582864
DOI: 10.1017/S0033291722001143 -
Menopause (New York, N.Y.) Aug 2023Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a subgroup of midlife women (age, 40-58 y) from Study E2006-G000-303 (Study 303; SUNRISE-2).
METHODS
This was a randomized, double-blind, placebo (PBO)-controlled (first 6 mo) study of adults with insomnia disorder ( N = 949). During treatment period 1 (TP1), participants received PBO or LEM 5 mg (LEM5) or 10 mg (LEM10). During TP2 (second 6 mo), LEM participants continued their assigned dose; PBO participants were rerandomized to LEM5 or LEM10. Assessments included patient-reported sleep- and fatigue-related measures and treatment-emergent adverse events.
RESULTS
The midlife female subgroup comprised 280 of 949 participants (TP1: PBO, n = 90 of 318 [28.3%]; LEM5, n = 82 of 316 [25.9%]; LEM10, n = 108 of 315 [34.3%]). At 6 months, median changes from baseline in subjective sleep-onset latency (in minutes) were -17.9, -20.7, and - 30.4 for PBO, LEM5, and LEM10 (vs PBO: LEM5, P = not significant; LEM10, P = 0.0310). At 6 months, mean changes from baseline in subjective wake after sleep onset (in minutes) were -37.0 (59.6), -50.1 (74.5), and -54.5 (65.4) for PBO, LEM5, and LEM10 (vs PBO: LEM5 and LEM10, P = not significant), with benefits sustained through 12 months. Greater decreases from baseline (improvement) in Insomnia Severity Index total score and Fatigue Severity Scale total score were seen with LEM versus PBO at 6 months; benefits continued through 12 months. Most treatment-emergent adverse events were mild to moderate in severity.
CONCLUSIONS
Consistent with the total population, subjective sleep parameters improved, and improvement was sustained over time in midlife women. LEM was well tolerated, suggesting that LEM may be a potential treatment option for midlife women with insomnia.
Topics: Adult; Female; Humans; Middle Aged; Double-Blind Method; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Menopause; Perimenopause
PubMed: 37339396
DOI: 10.1097/GME.0000000000002209 -
Frontiers in Bioscience (Scholar... Jan 2011Perimenopause, rather than a time of declining estrogen, is characterized by three major hormonal changes that may begin in regularly menstruating women in their... (Review)
Review
Perimenopause, rather than a time of declining estrogen, is characterized by three major hormonal changes that may begin in regularly menstruating women in their mid-thirties: erratically higher estradiol levels, decreased progesterone levels (in normally ovulatory, short luteal phase or anovulatory cycles), and disturbed ovarian-pituitary-hypothalamic feedback relationships. Recent data show that approximately a third of all perimenopausal cycles have a major surge in estradiol occurring de novo during the luteal phase. This phenomenon, named "luteal out of phase (LOOP)" event, may explain a large proportion of symptoms and signs for symptomatic perimenopausal women. Large urinary hormone data-sets from women studied yearly over a number of years in the Study of Women Across the Nation (SWAN) and in the Tremin data will eventually provide a more clear prospective understanding of within-woman hormonal changes. Predicting menopause proximity with FSH or Inhibin B levels is documented to be ineffective. Anti-Mullerian hormone levels may prove predictive. Finally, there is an urgent need to change perimenopause understandings, language and therapies used for midlife women's symptoms to reflect these hormonal changes.
Topics: Adult; Estrogens; Female; Follicle Stimulating Hormone; Hot Flashes; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Ovulation; Perimenopause; Progesterone; Weight Gain
PubMed: 21196391
DOI: 10.2741/s166 -
Medicine Aug 2023The issues related to the treatment of perimenopausal depression (PMD) are the side effects of antidepressants and hormone replacement therapy. The aim of this study was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The issues related to the treatment of perimenopausal depression (PMD) are the side effects of antidepressants and hormone replacement therapy. The aim of this study was to assess the efficiency and safety of acupuncture and moxibustion in PMD patients.
METHODS
Databases, namely PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, CBM, VIP, and WanFang, were reviewed for related randomized controlled trials dated between database inception and November 22, 2022. The primary outcomes were the efficacy rate and the Hamilton Depression Scale score. The secondary outcomes were the levels of follicle-stimulating hormone, luteinizing hormone, and estradiol and the Kupperman score. Odds ratios (ORs) were generated as the effect size for dichotomous outcomes, while the standard mean difference (SMD) ± standard deviation was used for continuous outcomes. Matrices were developed to demonstrate pairwise comparisons of regimens related to each endpoint. Utilizing Review Manager (RevMan) 5.3, Stata 16.0 and SPSS 21, data were analyzed.
RESULTS
In total, 27 studies involving 2269 PMD patients and 8 therapeutic measures were incorporated into the network meta-analysis (NMA). The NMA showed that warm acupuncture (OR = 1.55, 95% CI: 1.00-2.44), electroacupuncture (OR = 1.34, 95% CI: 1.00-1.8), abdominal acupuncture (OR = 1.19, 95% CI: 0.73-1.96), and common acupuncture (OR = 1.4, 95% CI: 0.9-2.17) were more effective than fluoxetine + menopausal hormone treatment in the treatment of PMD. The NMA also showed that, based on the Hamilton Depression Scale score, warm acupuncture was more effective than the other 4 acupuncture-related treatments, i.e., electroacupuncture (SMD = -1.22, 95% CI: -2.34 to -0.09), thread embedding (SMD = -1.31, 95% CI: -2.21 to -0.40), abdominal acupuncture (SMD = -1.33, 95% CI: -2.42 to -0.24), and common acupuncture (SMD = -1.46, 95% CI: -2.26 to -0.66). The cumulative ranking probability (SUCRA) showed that warm acupuncture (99.6%) was the best treatment method.
CONCLUSIONS
The findings of this network meta-analysis may help patients and therapists choose the best acupuncture therapy for treating perimenopausal depression patients and furnish reliable evidence for guidelines.
Topics: Humans; Network Meta-Analysis; Depression; Perimenopause; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Acupuncture Therapy
PubMed: 37603500
DOI: 10.1097/MD.0000000000034694 -
Diabetes & Metabolism Journal Jul 2021Cardiovascular disease is the primary cause of mortality in women and men with diabetes. Due to age and worsening of risk factors over the menopausal transition, risk of... (Review)
Review
Cardiovascular disease is the primary cause of mortality in women and men with diabetes. Due to age and worsening of risk factors over the menopausal transition, risk of coronary heart disease events increases in postmenopausal women with diabetes. Randomized studies have conflicted regarding the beneficial impact of estrogen therapy upon intermediate cardiovascular disease markers and events. Therefore, estrogen therapy is not currently recommended for indications other than symptom management. However, for women at low risk of adverse events, estrogen therapy can be used to minimize menopausal symptoms. The risk of adverse events can be estimated using risk engines for the calculation of cardiovascular risk and breast cancer risk in conjunction with screening tools such as mammography. Use of estrogen therapy, statins, and anti-platelet agents can be guided by such calculators particularly for younger women with diabetes. Risk management remains focused upon lifestyle behaviors and achieving optimal levels of cardiovascular risk factors, including lipids, glucose, and blood pressure. Use of pharmacologic therapies to address these risk factors, particularly specific hypoglycemic agents, may provide some additional benefit for risk prevention. The minimal benefit for women with limited life expectancy and risk of complications with intensive therapy should also be considered.
Topics: Cardiovascular Diseases; Diabetes Mellitus; Female; Heart Disease Risk Factors; Humans; Perimenopause
PubMed: 34352986
DOI: 10.4093/dmj.2020.0262 -
Fertility and Sterility Nov 2019Fractures and their consequences are the clinically important manifestation of osteoporosis; preventing fractures is the primary goal of management. Effective management... (Review)
Review
Fractures and their consequences are the clinically important manifestation of osteoporosis; preventing fractures is the primary goal of management. Effective management is achievable given present knowledge and tools but is seldom prescribed. This review will cover the individual and social burden of fracture, essential information about fracture risk and its estimation, an approach to patient care emphasizing specific information to elicit and therapeutic strategies to pursue, and existing gaps in knowledge and important questions for future research.
Topics: Adult; Bone Density; Disease Management; Female; Fractures, Bone; Humans; Middle Aged; Perimenopause; Postmenopause; Risk Factors
PubMed: 31731932
DOI: 10.1016/j.fertnstert.2019.09.038