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Obstetrics and Gynecology Sep 2023To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of...
OBJECTIVE
To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM).
DATA SOURCES
MEDLINE, EMBASE, ClinicalTrials.gov , and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators.
METHODS OF STUDY SELECTION
We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group.
TABULATION, INTEGRATION, AND RESULTS
Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO 2 ) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO 2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function.
CONCLUSION
Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.
Topics: Female; Humans; Hyaluronic Acid; Menopause; Vagina; Estrogens; Testosterone; Dehydroepiandrosterone
PubMed: 37543737
DOI: 10.1097/AOG.0000000000005288 -
Neuroscience and Biobehavioral Reviews Nov 2021Anxiety and stress-related disorders are more prevalent in women and associated with negative emotional memory consolidation as well as impaired fear extinction recall.... (Meta-Analysis)
Meta-Analysis Review
Anxiety and stress-related disorders are more prevalent in women and associated with negative emotional memory consolidation as well as impaired fear extinction recall. Recent research has identified a role of gonadal steroid hormones in influencing emotional memories and fear extinction, however most individual studies have small samples and employed various protocols. A systematic review and meta-analysis were conducted on studies that examined sex hormones (estrogen, progesterone, testosterone, allopregnanolone, dehydroepiandrosterone) on four aspects of memory, namely, intentional recall (k = 13), recognition memory (k = 7), intrusive memories (k = 9), and extinction recall (k = 11). The meta-analysis on natural cycling women revealed that progesterone level was positively associated with negative recall and negative intrusive memories, and this effect on intentional recall was enhanced under stress induction. Estradiol level was positively associated with extinction recall. This study reveals an important role of progesterone and estradiol in influencing emotional memory consolidation. It highlights the need to control for these hormonal effects and examine progesterone and estradiol concurrently across all menstrual phases in future emotional memory paradigms.
Topics: Estradiol; Extinction, Psychological; Fear; Female; Gonadal Steroid Hormones; Humans; Memory Consolidation; Menstrual Cycle; Progesterone
PubMed: 34517034
DOI: 10.1016/j.neubiorev.2021.09.010 -
Nicotine & Tobacco Research : Official... Oct 2022It is established that higher prediagnostic circulating androgen and estrogen levels are associated with increased breast cancer risk in premenopausal and postmenopausal... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
It is established that higher prediagnostic circulating androgen and estrogen levels are associated with increased breast cancer risk in premenopausal and postmenopausal women. Pooled analyses in postmenopausal women report higher androgen and estrogen levels in current heavy cigarette smokers compared to nonsmokers. However, evidence among premenopausal women has been inconsistent.
AIMS AND METHODS
We conducted a systematic review and meta-analysis to estimate differences in standardized mean hormone levels among current premenopausal smokers compared to nonsmokers. We reviewed and collated publications with sex hormone levels by smoking status among healthy, premenopausal women who were nonusers of exogenous hormones, including oral contraceptives, using PubMed through December 2019. A random effects meta-analysis was conducted to combine the standardized mean differences (SMD) and 95% confidence intervals (CIs) for estradiol, progesterone, testosterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and sex hormone-binding globulin by smoking status. Findings were summarized by menstrual cycle phase and overall.
RESULTS
Nineteen published peer-reviewed articles were included. Significantly increased testosterone levels among smokers compared to nonsmokers were identified from cross-sectional studies with varied menstrual phase timing (SMD 0.14; 95% CI 0.0005, 0.29) and significantly increased dehydroepiandrosterone-sulfate levels were found over all phases (SMD 0.12; 95% CI 0.01, 0.22). However, substantial heterogeneity existed in these studies.
CONCLUSIONS
This meta-analysis suggests that smoking may increase blood androgen levels in healthy premenopausal women which may increase breast cancer risk; however, the differences were modest. Larger and covariate-adjusted studies with standardized collection over the menstrual cycle are needed to better understand this relationship and to reduce heterogeneity.
IMPLICATIONS
Existing research has described associations between high prediagnostic estradiol and androgen levels with breast cancer risk among premenopausal women and has established active smoking as a breast cancer risk factor. However, the smoking and circulating sex hormone associations among premenopausal women remain inadequately studied. In this meta-analysis, we identified an association between smoking and higher mean testosterone and dehydroepiandrosterone-sulfate levels with consideration of menstrual phase, providing additional information on smoking's potential pathway to premenopausal breast cancer.
Topics: Female; Humans; Sex Hormone-Binding Globulin; Androgens; Progesterone; Cross-Sectional Studies; Gonadal Steroid Hormones; Estradiol; Testosterone; Breast Neoplasms; Estrogens; Smoking; Dehydroepiandrosterone; Contraceptives, Oral; Sulfates
PubMed: 35291014
DOI: 10.1093/ntr/ntac066 -
Menopause (New York, N.Y.) Mar 2023The associations between endogenous dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), and depression in older women are uncertain. However, DHEA supplements are...
IMPORTANCE
The associations between endogenous dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), and depression in older women are uncertain. However, DHEA supplements are widely available over the counter in some countries, and some people may be taking DHEA with the hope of positive mood effects.
OBJECTIVE
This systematic review aimed to investigate the association between endogenous DHEA/DHEAS blood concentrations and depression/depressive symptoms in community-dwelling postmenopausal women.Evidence Review: Searches were conducted in Ovid MEDLINE, EMBASE, PsycINFO, and Web of Science databases for observational studies with at least 100 community-dwelling participants until March 9, 2022. The bibliographies of retrieved articles were manually searched. The studies published in English and meeting the inclusion criteria were included in the review. The risk of bias was assessed with the modified Hoy tool for cross-sectional designs and the Joanna Briggs Institute modified critical appraisal checklist for cohort studies.
FINDINGS
Of the 30 articles retrieved for full-text review, 14 met the criteria for inclusion. Seven studies were cross-sectional, six were longitudinal, and one had both cross-sectional and longitudinal data. Five of eight cross-sectional studies found no association between DHEAS and depression, whereas three studies reported an inverse association. Similarly, most of the studies (n = 4) with longitudinal data reported no association, whereas two studies reported either an inverse association or mixed results for DHEAS and depression severity. No association between DHEA and depression was found irrespective of the study design. Heterogeneity of design was a barrier to meta-analysis and between study comparison. The majority of studies were limited by high risk of bias in at least one assessed domain.
CONCLUSION AND RELEVANCE
This systematic review does not support an association between endogenous DHEA/DHEAS and depression in postmenopausal women.
Topics: Aged; Female; Humans; Affect; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Depression; Postmenopause; Observational Studies as Topic
PubMed: 36649577
DOI: 10.1097/GME.0000000000002142 -
Gynecological Endocrinology : the... Dec 2023This systematic review and meta-analysis aimed at summarizing the evidence concerning circulating asprosin, and related endocrine and metabolites in women with and... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed at summarizing the evidence concerning circulating asprosin, and related endocrine and metabolites in women with and without the polycystic ovary syndrome (PCOS). We performed a comprehensive literature search in Pubmed, Web of Science, Scielo, and Chinese National Knowledge Infrastructure for studies published until May 20, 2022, that evaluated circulating asprosin levels in women with and without PCOS, regardless of language. The quality of studies was assessed with the Newcastle-Ottawa Scale. Random-effects models were used to estimate mean differences (MD) or standardized MD (SMD) and their 95% confidence interval (CI). We evaluated eight studies reporting 1,050 PCOS cases and 796 controls of reproductive age. Participants with PCOS were younger (MD = -2.40 years, 95% CI -2.46 to -2.33), with higher values of asprosin (SMD = 2.57, 95% CI 1.64-3.50), insulin (SMD = 2.73, 95% CI 1.18-4.28), homeostatic model assessment of insulin resistance (SMD = 2.70, 95% CI 0.85-4.55), luteinizing hormone (SMD = 2.33, 95% CI 0.60-4.06), total testosterone (SMD = 4.06, 95% CI 1.89-6.22), dehydroepiandrosterone sulfate (SMD = 2.38, 95% CI 0.37-4.40), and triglycerides (SMD = 1.20, 95% CI 0.13 to 2.27). Moreover, PCOS women had lower circulating levels of sex hormone-binding globulin (SMD = -3.36, 95% CI -4.92 to -1.80), and high-density lipoprotein-cholesterol (SMD = -0.85, 95% CI -1.69 to -0.01); with no significant differences observed for glucose, total cholesterol, and low-density lipoprotein-cholesterol levels. Circulating asprosin levels were significantly higher in women with PCOS as compared to those without the syndrome.
Topics: Female; Humans; Cholesterol, HDL; Insulin; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome
PubMed: 36480935
DOI: 10.1080/09513590.2022.2152790 -
The International Journal of Eating... Jun 2022This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation as a treatment for bone health in women with AN.
METHOD
Studies were retrieved from the PubMed, Embase, Cochrane Library, MEDLINE, and Scopus databases from inception to February 14, 2022. Observational studies that compared serum DHEA levels between women with AN and healthy controls were included for meta-analysis, and randomized controlled trials (RCTs) that evaluated the effects of DHEA supplementation on bone mass were reviewed.
RESULTS
Meta-analysis of 15 cross-sectional studies revealed that patients with AN had significantly elevated serum DHEA levels (mean difference (MD) = 311.63 ng/dl; 95% confidence interval (CI), 78.01-545.25) and reduced DHEAS levels (MD = -24.90 μg/dl; 95% CI, -41.72 to -8.07) compared with healthy controls. A systematic review of seven RCTs found that DHEA monotherapy does not improve bone mineral density (BMD) compared with placebo after adjusting for weight gain. While the combination of DHEA and conjugated oral contraceptives has led to increased bone strength and decreased bone loss, the beneficial effect appears to be limited to older adolescents and adults with closed physes. Potential detrimental effects on BMD were identified in younger adolescents with open physes in one study.
DISCUSSION
Due to the lack of apparent benefit of DHEA in women with AN and its potential detrimental effect on BMD in young patients with AN, current evidence does not support the use of DHEA.
PUBLIC SIGNIFICANCE
This study demonstrates that women with anorexia nervosa have abnormal levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which have been suggested by previous studies to play a role in the development of low bone density in this condition. However, current evidence does not support the use of DHEA as a treatment to preserve bone health in patients with anorexia nervosa given the lack of clear benefit following its use and also because of a potential detrimental effect on bone mineral density in young patients with anorexia nervosa.
Topics: Adolescent; Adult; Anorexia Nervosa; Bone Density; Dehydroepiandrosterone; Dietary Supplements; Female; Humans
PubMed: 35460091
DOI: 10.1002/eat.23714 -
Metabolites Sep 2019Steroidomics, an analytical technique for steroid biomarker mining, has received much attention in recent years. This systematic review and functional analysis,... (Review)
Review
Steroidomics, an analytical technique for steroid biomarker mining, has received much attention in recent years. This systematic review and functional analysis, following the PRISMA statement, aims to provide a comprehensive review and an appraisal of the developments and fundamental issues in steroid high-throughput analysis, with a focus on cancer research. We also discuss potential pitfalls and proposed recommendations for steroidomics-based clinical research. Forty-five studies met our inclusion criteria, with a focus on 12 types of cancer. Most studies focused on cancer risk prediction, followed by diagnosis, prognosis, and therapy monitoring. Prostate cancer was the most frequently studied cancer. Estradiol, dehydroepiandrosterone, and cortisol were mostly reported and altered in at least four types of cancer. Estrogen and estrogen metabolites were highly reported to associate with women-related cancers. Pathway enrichment analysis revealed that steroidogenesis; androgen and estrogen metabolism; and androstenedione metabolism were significantly altered in cancers. Our findings indicated that estradiol, dehydroepiandrosterone, cortisol, and estrogen metabolites, among others, could be considered oncosteroids. Despite noble achievements, significant shortcomings among the investigated studies were small sample sizes, cross-sectional designs, potential confounding factors, and problematic statistical approaches. More efforts are required to establish standardized procedures regarding study design, analytical procedures, and statistical inference.
PubMed: 31546652
DOI: 10.3390/metabo9100199 -
Journal of Comorbidity 2018Multimorbidity is the co-occurrence of two or more diseases in the same individual. One method to identify this condition at an early stage is the use of specific... (Review)
Review
BACKGROUND
Multimorbidity is the co-occurrence of two or more diseases in the same individual. One method to identify this condition at an early stage is the use of specific markers for various combinations of morbidities. Nonetheless, evidence related to physiological markers in multimorbidity is limited.
OBJECTIVE
The aim was to perform a systematic review to identify physiological markers associated with multimorbidity.
DESIGN
Articles available on PubMed, Register of Controlled Trials, Academic Search Premier, CINAHL, Scopus, SocINDEX, Web of Science, LILACS, and SciELO, from their inception to May 2018, were systematically searched and reviewed. The project was registered in PROSPERO under the number CRD42017055522.
RESULTS
The systematic search identified 922 papers. After evaluation, 18 articles were included in the full review reporting at least one physiological marker in coexisting diseases or which are strongly associated with the presence of multimorbidity in the future. Only five of these studies examined multimorbidity in general, identifying five physiological markers associated with multimorbidity, namely, dehydroepiandrosterone sulfate (DHEAS), interleukin 6 (IL-6), C-reactive protein (CRP), lipoprotein (Lp), and cystatin C (Cyst-C).
CONCLUSIONS
There is a paucity of studies related to physiological markers in multimorbidity. DHEAS, IL-6, CRP, Lp, and Cyst-C could be the initial focus for further investigation of physiological markers related to multimorbidity.
PubMed: 30364915
DOI: 10.1177/2235042X18806986 -
Journal of Clinical and Experimental... Jan 2023Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A... (Review)
Review
BACKGROUND
Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A variety of topical and systemic therapies have been tried to restore/stimulate the gland function or replace saliva reducing the symptoms of xerostomia and to avoid the problems of diminished salivary flow.
MATERIAL AND METHODS
Four search engines (PUBMED/Medline, EMBASE, Google Scholar and The Cochrane) were used in conducting a systematic review using the terms "Sjogren's syndrome" with the combination of other terms. To define these study acceptability criteria, we used PICO model (Population, Intervention, Control and Outcome) and study design technique.
RESULTS
Out of 47 articles initially screened, 28 studies met our selection criteria. Included studies showed positive results with interventions such as pilocarpine, rituximab, and interferon-alpha (IFN-α) for enhancing salivary flow and lacrimal secretion in SS condition. One study showed promising results for combination of prednisone and hydroxychloroquine in SS, however dose of prednisone is recommended to be tapered. Another study demonstrated comparable effects of dehydroepiandrosterone and the placebo in alleviation of dry mouth symptoms (=0.006). Therapeutic effects have been reported with LASER therapy.
CONCLUSIONS
Pilocarpine was found to be highly beneficial whereas, rituximab and IFN-α were moderately effective in the reduction of hyposalivation in SS patient. Adverse events were common. Use of any alternative modalities for the management cannot be supported based on the current evidence; this demands more studies in future to be conducted staking into account adverse effects which might occur particularly with the pharmacological therapies. Sjogren's Syndrome, Xerostomia, Hyposalivation, Pilocarpine, Rituximab, Sialagogue.
PubMed: 36755678
DOI: 10.4317/jced.59891 -
Testosterone, DHEA and DHEA-S in patients with schizophrenia: A systematic review and meta-analysis.Psychoneuroendocrinology Mar 2018Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) might play an important role in the pathophysiology of... (Meta-Analysis)
Meta-Analysis Review
Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) might play an important role in the pathophysiology of schizophrenia. Therefore, we performed a systematic review and meta-analysis of studies comparing the levels of testosterone, DHEA and DHEA-S in patients with schizophrenia and healthy controls. We searched electronic databases from their inception until Oct 29, 2017. Effect size (ES) estimates were calculated as Hedges' g. Data analysis was performed using random-effects models. Our analysis included 34 eligible studies, representing 1742 patients and 1604 controls. Main analysis revealed elevated DHEA-S levels in the whole group of patients (ES = 0.75, 95%CI: 0.23-1.28, p = 0.005). In subgroup analyses, patients with first-episode psychosis (FEP) had significantly higher levels of free testosterone (ES = 1.21, 95%CI: 0.30-2.12, p = 0.009) and DHEA-S (ES = 1.19, 95%CI: 0.66-1.71, p < 0.001). Acutely relapsed schizophrenia patients presented significantly higher levels of total testosterone (ES = 0.50, 95%CI: 0.21-0.70, p < 0.001). Total testosterone levels were also elevated in stable multi-episode schizophrenia (sMES) females (ES = 0.56, 95%CI: 0.33-0.80, p < 0.001) and reduced in sMES males (ES = -0.62, 95%CI: -1.07 to 0.18, p = 0.006). Increased levels of biologically active, free testosterone and DHEA-S in FEP suggest that these alterations might appear as a response to stress that becomes blunted during subsequent exacerbations of schizophrenia. Differential changes in total testosterone levels in male and female sMES patients might represent medication effects related to prolactin-releasing effects of antipsychotics.
Topics: Adult; Antipsychotic Agents; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Middle Aged; Schizophrenia; Testosterone
PubMed: 29334627
DOI: 10.1016/j.psyneuen.2018.01.007