-
Current Psychiatry Reports Nov 2019We review recent data on bipolar disorder in menopausal-aged women, particularly in women undergoing the menopausal transition (MT). We discuss evidence on the severity... (Review)
Review
PURPOSE OF REVIEW
We review recent data on bipolar disorder in menopausal-aged women, particularly in women undergoing the menopausal transition (MT). We discuss evidence on the severity of symptoms in bipolar women during the MT. Moreover, we address two factors in bipolar disorder and menopausal research: standardized menopausal staging and women's conceptualization of their menopausal and bipolar symptoms.
RECENT FINDINGS
While there are few studies within the last 5 years on bipolar women undergoing the MT, new evidence suggest that mood symptoms in women worsen with progression through the MT. Consistent use of the standardized menopausal staging system can facilitate understanding of the timing of worsening symptoms. Moreover, whether women conceptualize their symptoms as arising from their MT or bipolar disorder can influence whether they seek hormonal therapy or psychiatric treatment, respectively. The MT is a potential time for mood instability in vulnerable women, which can manifest as first-onset development of bipolar disorder or increased symptom severity in women with pre-existing bipolar disorder. Adoption of a standardized menopausal staging may offer novel frameworks for understanding of the role of the MT in bipolar disorder.
Topics: Bipolar Disorder; Female; Humans; Middle Aged; Perimenopause
PubMed: 31768664
DOI: 10.1007/s11920-019-1111-3 -
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 -
The Cochrane Database of Systematic... Aug 2023The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. This review is an update of a review first published in... (Review)
Review
BACKGROUND
The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. This review is an update of a review first published in 2013.
OBJECTIVES
We aimed to assess the effect of hormone therapy on sexual function in perimenopausal and postmenopausal women.
SEARCH METHODS
On 19 December 2022 we searched the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Science, two trials registries, and OpenGrey, together with reference checking and contact with experts in the field for any additional studies.
SELECTION CRITERIA
We included randomized controlled trials that compared hormone therapy to either placebo or no intervention (control) using any validated assessment tool to evaluate sexual function. We considered hormone therapy: estrogen alone; estrogen in combination with progestogens; synthetic steroids, for example, tibolone; selective estrogen receptor modulators (SERMs), for example, raloxifene, bazedoxifene; and SERMs in combination with estrogen.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. We analyzed data using mean differences (MDs) and standardized mean differences (SMDs). The primary outcome was the sexual function score. Secondary outcomes were the domains of sexual response: desire; arousal; lubrication; orgasm; satisfaction; and pain. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 36 studies (23,299 women; 12,225 intervention group; 11,074 control group), of which 35 evaluated postmenopausal women; only one study evaluated perimenopausal women. The 'symptomatic or early postmenopausal women' subgroup included 10 studies, which included women experiencing menopausal symptoms (symptoms such as hot flushes, night sweats, sleep disturbance, vaginal atrophy, and dyspareunia) or early postmenopausal women (within five years after menopause). The 'unselected postmenopausal women' subgroup included 26 studies, which included women regardless of menopausal symptoms and women whose last menstrual period was more than five years earlier. No study included only women with sexual dysfunction and only seven studies evaluated sexual function as a primary outcome. We deemed 20 studies at high risk of bias, two studies at low risk, and the other 14 studies at unclear risk of bias. Nineteen studies received commercial funding. Estrogen alone versus control probably slightly improves the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.50, 95% confidence interval (CI) (0.04 to 0.96; I² = 88%; 3 studies, 699 women; moderate-quality evidence), and probably makes little or no difference to the sexual function composite score in unselected postmenopausal women (SMD 0.64, 95% CI -0.12 to 1.41; I² = 94%; 6 studies, 608 women; moderate-quality evidence). The pooled result suggests that estrogen alone versus placebo or no intervention probably slightly improves sexual function composite score (SMD 0.60, 95% CI 0.16 to 1.04; I² = 92%; 9 studies, 1307 women, moderate-quality evidence). We are uncertain of the effect of estrogen combined with progestogens versus placebo or no intervention on the sexual function composite score in unselected postmenopausal women (MD 0.08 95% CI -1.52 to 1.68; 1 study, 104 women; very low-quality evidence). We are uncertain of the effect of synthetic steroids versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 1.32, 95% CI 1.18 to 1.47; 1 study, 883 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 0.46, 95% CI 0.07 to 0.85; 1 study, 105 women; very low-quality evidence). We are uncertain of the effect of SERMs versus control on the sexual function composite score in symptomatic or early postmenopausal women (MD -1.00, 95% CI -2.00 to -0.00; 1 study, 215 women; very low-quality evidence) and of their effect in unselected postmenopausal women (MD 2.24, 95% 1.37 to 3.11 2 studies, 1525 women, I² = 1%, low-quality evidence). We are uncertain of the effect of SERMs combined with estrogen versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.22, 95% CI 0.00 to 0.43; 1 study, 542 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 2.79, 95% CI 2.41 to 3.18; 1 study, 272 women; very low-quality evidence). The observed heterogeneity in many analyses may be caused by variations in the interventions and doses used, and by different tools used for assessment.
AUTHORS' CONCLUSIONS
Hormone therapy treatment with estrogen alone probably slightly improves the sexual function composite score in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), and in unselected postmenopausal women, especially in the lubrication, pain, and satisfaction domains. We are uncertain whether estrogen combined with progestogens improves the sexual function composite score in unselected postmenopausal women. Evidence regarding other hormone therapies (synthetic steroids and SERMs) is of very low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest the beneficial effects of synthetic steroids (for example tibolone) or SERMs alone or combined with estrogen on sexual function. More studies that evaluate the effect of estrogen combined with progestogens, synthetic steroids, SERMs, and SERMs combined with estrogen would improve the quality of the evidence for the effect of these treatments on sexual function in perimenopausal and postmenopausal women.
Topics: Female; Humans; Estrogens; Perimenopause; Postmenopause; Progestins; Selective Estrogen Receptor Modulators
PubMed: 37619252
DOI: 10.1002/14651858.CD009672.pub3 -
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 -
Menopause (New York, N.Y.) Jan 2021To evaluate the effects of sex hormones on amplitude of low-frequency fluctuation (ALFF) in brain regions related to cognition in perimenopausal women.
OBJECTIVE
To evaluate the effects of sex hormones on amplitude of low-frequency fluctuation (ALFF) in brain regions related to cognition in perimenopausal women.
METHODS
This cross-sectional study involved 25 perimenopausal women and 25 premenopausal women who underwent behavioral evaluations, sex hormone level measurements, and functional magnetic resonance imaging (fMRI). All data and ALFF analyses were preprocessed using the Data Processing Assistant for Resting-State fMRI. Statistical analyses were performed using the Resting-State fMRI Data Analysis Toolkit to explore the differences in ALFF between perimenopausal and premenopausal women. The gray matter volume (GMV) values extracted from brain regions (regions of interest) with significantly different ALFF values between the perimenopausal and premenopausal groups were compared. We analyzed the correlations of the ALFF and GMV values of these regions of interest with the results of behavioral evaluations and sex hormone levels in the two groups.
RESULTS
Compared with the premenopausal group, the perimenopausal group showed significant ALFF increase in the left gyrus rectus. Regions with decreased ALFF in the perimenopausal group included the left superior temporal gyrus, left inferior frontal gyrus, and left insula. The GMV values of the left gyrus rectus and left superior temporal gyrus were reduced in perimenopausal women. Furthermore, the estradiol level was negatively correlated with the ALFF value of the left gyrus rectus in perimenopausal women.
CONCLUSIONS
The ALFF and GMV values of certain brain regions related to cognitive function were changed in perimenopausal women. Such functional brain alterations may provide more information regarding the mechanism of cognitive dysfunction in perimenopausal women.
Topics: Brain; Cross-Sectional Studies; Female; Gonadal Steroid Hormones; Humans; Magnetic Resonance Imaging; Perimenopause
PubMed: 33438891
DOI: 10.1097/GME.0000000000001720 -
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 -
Journal of Food Biochemistry Dec 2020The present randomized, double-blinded, placebo-controlled study investigated the effect of a standardized fenugreek extract (FHE) on perimenopausal discomforts and its... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled study.
The present randomized, double-blinded, placebo-controlled study investigated the effect of a standardized fenugreek extract (FHE) on perimenopausal discomforts and its influence on hormonal balance and safety. Healthy women characterized with perimenopausal symptoms (n = 48), as assessed by MRS questionnaire, were randomized either to FHE (n = 24) or placebo (n = 24) and supplemented with 250 mg × 2/day for 42 days. Both inter and intra-group comparison revealed a significant improvement in somatic, psychological, and urogenital scores in FHE group, especially for hot flashes (25.9%), night sweats (26.5%), depression (31.8%), and insomnia (21.6%). Further hormone analysis revealed an enhancement in serum estradiol (18.9%), free testosterone (38.2%), and progesterone (19.9%) concentrations and a significant decrease in FSH (38.2%) and SHBG (21.1%) concentrations toward establishing a hormonal balance among FHE-group; without significant changes in other clinical safety parameters. Thus, FHE supplementation offered a significant reduction in vasomotor effects and depression in perimenopausal women, without any adverse effects PRACTICAL APPLICATIONS: Fenugreek is a popular kitchen spice and Ayurvedic medicine for a variety of health conditions including diabetes, hypercholesterolemia, hepatotoxicity, gastritis, and also for a variety of hormone-related health conditions such as sexual functions, lactation, osteoporosis, PCOS, and post/perimenopausal discomforts. Fenugreek is rich in alkaloids, steroidal saponins, flavonoids and 4-hydroxyisoleucine. The present randomized-controlled study investigated the plausible application of a standardized hydro-ethanolic extract of fenugreek seeds (FHE) having a unique 3:1 ratio for protodioscin to trigonelline in the management of perimenopausal discomforts. It was observed that FHE at a dosage of 250 mg × 2/day for 42 days significantly reduced the discomforts, especially vasomotor symptoms and depression, and helped to attain a hormonal balance without any adverse effects or deviations in clinical safety parameters. Thus, FHE could be a potential natural agent for the management of post and perimenopausal discomforts and has to be explored in future studies.
Topics: Depression; Double-Blind Method; Female; Hot Flashes; Humans; Perimenopause; Plant Extracts; Trigonella
PubMed: 33025616
DOI: 10.1111/jfbc.13507 -
Annals of Palliative Medicine Jan 2022The quality of life of women is seriously affected by perimenopausal symptoms and related diseases. The work of female clinical nurses is often stressful and job burnout...
BACKGROUND
The quality of life of women is seriously affected by perimenopausal symptoms and related diseases. The work of female clinical nurses is often stressful and job burnout is not uncommon. Under such conditions, perimenopausal syndrome can be easily induced or aggravated. The health of nurses is positively correlated with nursing quality, residents' health, patients' quality of life and human resource cost in health care institutions. The physical and mental health of perimenopausal nurses is an important issue worth paying attention to.
METHODS
Clinical nurses were selected from tertiary and secondary hospitals in Chongqing province by purposive sampling from September to November 2020. Front-line nurses diagnosed with perimenopausal syndrome were recruited from different clinical departments and interviewed using a semi-structured method. The interview results were processed using thematic analysis.
RESULTS
Finally, 16 nurses were included in the present study. Analysis of the interview transcriptions identified four themes: patient factors, work environment factors, personal factors, and family social support factors.
CONCLUSIONS
The themes influencing perimenopausal syndrome in clinical nurses include aspects of patient factors, working environment factors, personal factors, and family social support factors. Our findings provide an important reference for policy makers to develop management programs that benefit nurses and ensure the safety of patients.
Topics: Burnout, Professional; Female; Humans; Nursing Staff, Hospital; Perimenopause; Qualitative Research; Quality of Life
PubMed: 35144406
DOI: 10.21037/apm-21-3572 -
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 -
BMC Infectious Diseases Nov 2021Blastocystis spp. are considered pathogenic or commensal organisms, although the majority of researchers suggest that these are neglected pathogens. The main aim of this...
BACKGROUND
Blastocystis spp. are considered pathogenic or commensal organisms, although the majority of researchers suggest that these are neglected pathogens. The main aim of this study was to determine the prevalence and subtype distribution of Blastocystis spp. in pre- and perimenopausal women, with respect to socio-demographic (age and place of residence), and epidemiological factors, as well as drinking tap water, contact with domestic animals, traveling abroad, health status, and presence of gastrointestinal symptoms. Additionally, the objective was to compare hematological and biochemical parameters of Blastocystis spp. infected and uninfected women.
METHODS
The study included 425 women aged 45-60. Their stool samples were examined microscopically and analyzed by a conventional polymerase chain reaction (cPCR).
RESULTS
Blastocystis spp. were detected in 6.1% of pre- and perimenopausal women. Molecular analysis of the stool samples identified seven Blastocystis subtypes (ST1-ST4, ST6, ST7, and ST9). Blastocystis subtypes 2 and 3 were the most prevalent. The presence of Blastocystis spp. was not significantly related to socio-demographic and epidemiological factors. There were also no significant associations between Blastocystis spp. and blood parameters, or gastrointestinal symptoms.
CONCLUSION
This study complements the limited available data on the prevalence of Blastocystis spp. in pre- and perimenopausal women. It is also the first report showing the presence of Blastocystis subtype 9 in Poland.
Topics: Animals; Blastocystis; Blastocystis Infections; Feces; Female; Genetic Variation; Humans; Perimenopause; Prevalence; Risk Factors
PubMed: 34724915
DOI: 10.1186/s12879-021-06815-z