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Post Reproductive Health Dec 2023Therapies utilised in breast cancer management have been found to induce or worsen the genitourinary symptoms of menopause (GSM), a group of physical symptoms associated... (Review)
Review
A systematic review of randomised clinical trials - The safety of vaginal hormones and selective estrogen receptor modulators for the treatment of genitourinary menopausal symptoms in breast cancer survivors.
Therapies utilised in breast cancer management have been found to induce or worsen the genitourinary symptoms of menopause (GSM), a group of physical symptoms associated with the systemic loss of estrogen. These symptoms are often undertreated due to concerns surrounding cancer recurrence, especially when considering treatments with possible pro-estrogenic effects. As breast cancer prognosis continues to improve, clinicians are increasingly focussing on managing these symptoms amongst survivors. This systematic review primarily aimed to determine the risk of breast cancer recurrence amongst survivors using vaginal hormones and selective estrogen receptor modulator therapies recommended for use in GSM in the United Kingdom amongst currently published randomised clinical trials (RCTs). The secondary aim was to determine whether these RCTs demonstrated a significant rise in serum estrogen levels following the use of these therapies. A literature search revealed three RCTs suitable for assessment, two evaluating vaginal estrogen and one evaluating vaginal DHEA treatment. Our review determined that amongst published RCTs, no studies have aimed to assess for breast cancer recurrence; however among the studies observing for serious adverse effects of vaginal estrogen preparations, none have reported an increased incidence. Furthermore, these studies did not report a persistent or significant increase in serum estrogen levels following the use of vaginal estrogen products and low concentration (3.25 mg/day) DHEA gel. Larger RCTs studying commonly used vaginal preparations and selective estrogen receptor modulator treatments for GSM over longer follow-up periods will be vital to better assess the risk of breast cancer recurrence in survivors receiving these treatments.
Topics: Female; Humans; Selective Estrogen Receptor Modulators; Cancer Survivors; Neoplasm Recurrence, Local; Breast Neoplasms; Estrogens; Menopause; Survivors; Dehydroepiandrosterone
PubMed: 37840298
DOI: 10.1177/20533691231208473 -
Frontiers in Nutrition 2023Synbiotics, refer to a combination of probiotics and prebiotics in a form of synergism that beneficially affect the host's health by alternating the composition and/or...
BACKGROUND
Synbiotics, refer to a combination of probiotics and prebiotics in a form of synergism that beneficially affect the host's health by alternating the composition and/or function of the gut microbiota. Numerous meta-analyses of randomized clinical trials have proven that pro, pre-, and synbiotics supplementation has health outcomes in women with polycystic ovary syndrome (PCOS). However, the strength and quality of this evidence in aggregate have not yet been synthesized in great detail.
METHODS
PubMed, Scopus, Web of Sciences, and Google Scholar were searched up to March 2023. We pooled the mean difference and its 95% confidence interval (CI) by applying a random-effects model.
RESULTS
Overall, nine meta-analyses including a total of 12 trials were identified. The results of the present study indicated that probiotic supplementation significantly reduced the homeostatic model assessment for insulin resistance (HOMA-IR; WMD: -0.29, 95% CI: -0.57 to -0.02, = 0.03, = 4; moderate certainty) and fasting glucose concentration (FGC; WMD: -7.5 mg/dL, 95% CI: -13.60 to -0.51, = 0.03; = 4; low certainty). Moreover, synbiotic supplementation had beneficial effects on glycemic control, lipid profile, and hormonal parameters, but the certainty of the evidence was rated as low to very low. However, supplementation with pro-/synbiotics did not affect inflammation and oxidative stress in women with PCOS. Furthermore, waist/hip circumference, fasting glucose concentration, lipid profile, dehydroepiandrosterone sulfate, high-sensitivity C-reactive protein, and hirsutism score were significantly reduced after prebiotics supplementation with low certainty of evidence.
CONCLUSION
Although pro-, pre-, and synbiotics supplementation had beneficial effects on some PCOS-related outcomes, the certainty of the evidence was rated as low to very low. Therefore, further well-designed RCTs might help to confirm our findings in women with PCOS.
PubMed: 37829729
DOI: 10.3389/fnut.2023.1178842 -
Menopause (New York, N.Y.) Nov 2023Whether dehydroepiandrosterone (DHEA) supplementation improves cognitive performance in older women is uncertain. Nonetheless, DHEA supplements are readily available...
IMPORTANCE
Whether dehydroepiandrosterone (DHEA) supplementation improves cognitive performance in older women is uncertain. Nonetheless, DHEA supplements are readily available over the counter in several countries and are potentially being used to prevent cognitive decline and dementia.
OBJECTIVE
This systematic review was conducted to evaluate the effect of exogenous DHEA on cognitive performance in postmenopausal women.
EVIDENCE REVIEW
Ovid MEDLINE, EMBASE, PsycINFO, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials databases were searched for studies of postmenopausal women until November 30, 2022. Eligible studies were required to be randomized clinical trials, be at least single blind, have a placebo or comparator arm and published in English. Risk of bias of the included studies was assessed by the revised Cochrane risk-of-bias tool.
FINDINGS
Of the 15 articles retrieved for full-text review, four met the inclusion criteria. In all studies DHEA was administered as a 50-mg oral daily dose and all were double blind with an identical placebo. Three were placebo-controlled, crossover studies and one was a parallel-group clinical trial. The only positive outcome was limited to a 4-wk cross-over study in which DHEA statistically significantly enhanced five of six tests of visual-spatial performance compared with placebo in 24 cognitively normal postmenopausal women. Improvement in cognitive performance with DHEA treatment over placebo group was not seen in any other study. Heterogeneity of design and use of multiple measures of cognitive performance was a barrier to meta-analysis and between study comparisons. The studies were limited by high risk of bias in multiple domains.
CONCLUSION AND RELEVANCE
Overall, this systematic review does not support a beneficial effect of DHEA therapy on cognitive performance in postmenopausal women.
Topics: Aged; Female; Humans; Cognition; Cognition Disorders; Cross-Over Studies; Dehydroepiandrosterone; Postmenopause; Randomized Controlled Trials as Topic; Single-Blind Method
PubMed: 37788418
DOI: 10.1097/GME.0000000000002251 -
Biomarkers in Body Fluids as Indicators of Skeletal Maturity: A Systematic Review and Meta-analysis.Rambam Maimonides Medical Journal Aug 2023This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard... (Review)
Review
OBJECTIVES
This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
MATERIALS AND METHODS
A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
RESULTS
A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
CONCLUSIONS
Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
PubMed: 37669407
DOI: 10.5041/RMMJ.10506 -
European Journal of Endocrinology Sep 2023Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in response to starvation and low body weight including changes in adrenocortical hormones. Our objective was to systematically review adrenocortical hormone levels in anorexia nervosa.
DESIGN/METHODS
We searched MEDLINE and EMBASE for studies that reported at least one adrenocortical hormone, including dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEA-S), progesterone, 17-hydroxyprogesterone, pregnenolone, cortisol (serum, urine, cerebrospinal fluid, and hair sample), aldosterone, androstenedione, and testosterone in patients with anorexia nervosa and normal-weight healthy controls from inception until October 2021. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). A pooled MD was then calculated by combining MDs of each study using the random-effects model.
RESULTS
We included a total of 101 studies with over 2500 females with anorexia nervosa. Mean cortisol levels were significantly higher in anorexia nervosa as compared to normal-weight controls for multiple forms of measurement, including morning cortisol, 12-hour and 24-hour pooled serum cortisol, 24-hour urine cortisol, and after an overnight dexamethasone suppression test. In contrast, mean serum total testosterone and DHEA-S levels were significantly lower among patients with anorexia nervosa.
CONCLUSIONS
Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.
Topics: Humans; Female; Anorexia Nervosa; Hydrocortisone; Aldosterone; Progesterone; Dehydroepiandrosterone Sulfate
PubMed: 37669399
DOI: 10.1093/ejendo/lvad123 -
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 -
Biomedicines Jul 2023A better understanding of interindividual differences and the development of targeted therapies is one of the major challenges of modern medicine. The sex of a person... (Review)
Review
A better understanding of interindividual differences and the development of targeted therapies is one of the major challenges of modern medicine. The sex of a person plays a crucial role in this regard. This systematic review aimed to summarise and analyse available evidence on the mutual interactions between non-invasive brain stimulation and sex/polypeptide hormones. The PubMed database was searched from its inception to 31 March 2023, for (i) studies that investigated the impact of sex and/or polypeptide hormones on the effects induced by non-invasive brain stimulation, or (ii) studies that investigated non-invasive brain stimulation in the modulation of sex and/or polypeptide hormones. Eighteen studies (319 healthy and 96 disabled participants) were included. Most studies focused on female sex hormone levels during the menstrual cycle. The later follicular phase is associated with a weak between hemispheric and intracortical inhibition, strong intracortical facilitation, and high stimulation-induced neural and behavioural changes. The opposite effects are observed during the luteal phase. In addition, the participant's sex, presence and/or absence of real ovulation and increase in oestradiol level by chorionic gonadotropin injection influence the stimulation-induced neurophysiological and behavioural effects. In Parkinson's disease and consciousness disorders, the repetitive application of non-invasive brain stimulation increases oestradiol and dehydroepiandrosterone levels and reduces disability. To date, male hormones have not been sufficiently included in these studies. Here, we show that the sex and/or polypeptide hormones and non-invasive brain stimulation methods are in reciprocal interactions. This may be used to create a more effective and individualised approach for healthy individuals and individuals with disabilities.
PubMed: 37509620
DOI: 10.3390/biomedicines11071981 -
Reproductive Biology and Endocrinology... Jul 2023Assisted reproductive technology (ART) has brought good news to infertile patients, but how to improve the pregnancy outcome of poor ovarian response (POR) patients is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Assisted reproductive technology (ART) has brought good news to infertile patients, but how to improve the pregnancy outcome of poor ovarian response (POR) patients is still a serious challenge and the scientific evidence of some adjuvant therapies remains controversial.
AIM
Based on previous evidence, the purpose of this systematic review and network meta-analysis was to evaluate the effects of DHEA, CoQ10, GH and TEAS on pregnancy outcomes in POR patients undergoing in vitro fertilization and embryo transplantation (IVF-ET). In addition, we aimed to determine the current optimal adjuvant treatment strategies for POR.
METHODS
PubMed, Embase, The Cochrane Library and four databases in China (CNKI, Wanfang, VIP, SinoMed) were systematically searched up to July 30, 2022, with no restrictions on language. We included randomized controlled trials (RCTs) of adjuvant treatment strategies (DHEA, CoQ10, GH and TEAS) before IVF-ET to improve pregnancy outcomes in POR patients, while the control group received a controlled ovarian stimulation (COS) regimen only. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The surface under the cumulative ranking curve (SUCRA) was used to provide a pooled measure of cumulative ranking for each outcome.
RESULTS
Sixteen RCTs (2323 women) with POR defined using the Bologna criteria were included in the network meta-analysis. Compared with the control group, CoQ10 (OR 2.22, 95% CI: 1.05 to 4.71) and DHEA (OR 1.92, 95% CI: 1.16 to 3.16) had obvious advantages in improving the clinical pregnancy rate. CoQ10 was the best in improving the live birth rate (OR 2.36, 95% CI: 1.07 to 5.38). DHEA increased the embryo implantation rate (OR 2.80, 95%CI: 1.41 to 5.57) and the high-quality embryo rate (OR 2.01, 95% CI: 1.07 to 3.78) and number of oocytes retrieved (WMD 1.63, 95% CI: 0.34 to 2.92) showed a greater advantage, with GH in second place. Several adjuvant treatment strategies had no significant effect on reducing the cycle canceling rate compared with the control group. TEAS was the least effective of the four adjuvant treatments in most pooled results, but the overall effect appeared to be better than that of the control group.
CONCLUSION
Compared with COS regimen, the adjuvant use of CoQ10, DHEA and GH before IVF may have a better clinical effect on the pregnancy outcome of POR patients. TEAS needs careful consideration in improving the clinical pregnancy rate. Future large-scale RCTs with direct comparisons are needed to validate or update this conclusion.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022304723.
Topics: Female; Pregnancy; Humans; Network Meta-Analysis; Ovulation Induction; Reproductive Techniques, Assisted; Fertilization in Vitro; Pregnancy Rate; Dehydroepiandrosterone
PubMed: 37464357
DOI: 10.1186/s12958-023-01119-0 -
Life (Basel, Switzerland) May 2023Despite many studies exploring the effects of DHEA supplementation, its application in IVF procedure continues to be a subject of debate owing to the inconsistent... (Review)
Review
Effects of Dehydroepiandrosterone (DHEA) Supplementation on Ovarian Cumulus Cells following In Vitro Fertilization (IVF)/Intra-Cytoplasmic Sperm Injection (ICSI) Treatment-A Systematic Review.
Despite many studies exploring the effects of DHEA supplementation, its application in IVF procedure continues to be a subject of debate owing to the inconsistent findings and the lack of rigorously designed, large-scale, randomized trials. Our review aims to explore the effectiveness of DHEA supplementation in ovarian cumulus cells following IVF/ICSI treatment. We conducted a literature search of Pub-Med, Ovid MEDLINE, and SCOPUS (inception to June 2022) for all relevant articles, including the keywords of "dehydroepiandrosterone/DHEA", "oocyte", and "cumulus cells". From the preliminary search, 69 publications were identified, and following a thorough screening process, seven studies were ultimately incorporated into the final review. Four hundred twenty-four women were enrolled in these studies, with DHEA supplementation being administered exclusively to women exhibiting poor ovarian response/diminished ovarian reserve or belonging to an older age demographic. The intervention in the studies was DHEA 75-90 mg daily for at least 8-12 weeks. The only randomized controlled trial showed no difference in clinical or cumulus cell-related outcomes between the control and treatment groups. However, the remaining six studies (two cohorts, four case-controls) showed significant beneficial effects of DHEA in cumulus cell-related outcomes compared to the group (older age or POR/DOR) without DHEA supplementation. All studies revealed no significant difference in stimulation and pregnancy outcomes. Our review concludes that DHEA supplementation did show beneficial effect on ovarian cumulus cells in improving oocyte quality for women of advanced age or with poor ovarian responders.
PubMed: 37374020
DOI: 10.3390/life13061237 -
Frontiers in Endocrinology 2023Dehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the evidence remains inconsistent. This study aimed to investigate the efficacy of DHEA supplementation in patients with POR/DOR undergoing IVF/ICSI.
METHODS
PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched up to October 2022.
RESULTS
A total of 32 studies were retrieved, including 14 RCTs, 11 self-controlled studies and 7 case-controlled studies. In the subgroup analysis of only RCTs, DHEA treatment significantly increased the number of antral follicle count (AFC) (weighted mean difference : WMD 1.18, 95% confidence interval(CI): 0.17 to 2.19, 0.022), while reduced the level of bFSH (WMD -1.99, 95% CI: -2.52 to -1.46, <0.001), the need of gonadotropin (Gn) doses (WMD -382.29, 95% CI: -644.82 to -119.76, 0.004), the days of stimulation (WMD -0.90, 95% CI: -1.34 to -0.47, <0.001) and miscarriage rate (relative risk : RR 0.46, 95% CI: 0.29 to 0.73, 0.001). The higher clinical pregnancy and live birth rates were found in the analysis of non-RCTs. However, there were no significant differences in the number of retrieved oocytes, the number of transferred embryos, and the clinical pregnancy and live birth rates in the subgroup analysis of only RCTs. Moreover, meta-regression analyses showed that women with lower basal FSH had more increase in serum FSH levels (b=-0.94, 95% CI: -1.62 to -0.25, 0.014), and women with higher baseline AMH levels had more increase in serum AMH levels (b=-0.60, 95% CI: -1.15 to -0.06, 0.035) after DHEA supplementation. In addition, the number of retrieved oocytes was higher in the studies on relatively younger women (b=-0.21, 95% CI: -0.39 to -0.03, 0.023) and small sample sizes (b=-0.003, 95% CI: -0.006 to -0.0003, 0.032).
CONCLUSIONS
DHEA treatment didn't significantly improve the live birth rate of women with DOR or POR undergoing IVF/ICSI in the subgroup analysis of only RCTs. The higher clinical pregnancy and live birth rates in those non-RCTs should be interpreted with caution because of potential bias. Further studies using more explicit criteria to subjects are needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD 42022384393.
Topics: Pregnancy; Humans; Female; Sperm Injections, Intracytoplasmic; Fertilization in Vitro; Pregnancy Rate; Ovulation Induction; Follicle Stimulating Hormone; Dehydroepiandrosterone
PubMed: 37361534
DOI: 10.3389/fendo.2023.1156280