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Ontario Health Technology Assessment... 2023Ovarian cancer affects the cells of the ovaries, and epithelial cancer is the most common type of malignant ovarian cancer. The homologous recombination repair pathway...
Homologous Recombination Deficiency Testing to Inform Patient Decisions About Niraparib Maintenance Therapy for High-Grade Serous or Endometrioid Epithelial Ovarian Cancer: A Health Technology Assessment.
BACKGROUND
Ovarian cancer affects the cells of the ovaries, and epithelial cancer is the most common type of malignant ovarian cancer. The homologous recombination repair pathway enables error-free repair of DNA double-strand breaks. Damage of key genes associated with this pathway leads to homologous recombination deficiency (HRD), which results in unrepaired DNA and can lead to cancer. Tumours with HRD are believed to be sensitive to treatment with poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors, such as niraparib. We conducted a health technology assessment to evaluate the clinical utility and cost-effectiveness of HRD testing to inform patient decisions about the use of niraparib maintenance therapy for patients with high-grade serous or endometrioid epithelial ovarian cancer. We also evaluated the efficacy and safety of niraparib maintenance therapy in patients with HRD or homologous recombination proficiency (HRP), the cost-effectiveness of HRD testing, the budget impact of publicly funding HRD testing, and patient preferences and values.
METHODS
We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool for randomized trials version 2, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis with a 5-year time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding HRD testing in people with ovarian cancer in Ontario. We performed a literature search for quantitative evidence of patient and provider preferences with respect to HRD testing and maintenance therapy with PARP inhibitors. To contextualize the potential value of HRD testing, we spoke with people with ovarian cancer.
RESULTS
The clinical evidence review included two studies in high-grade epithelial ovarian cancer (one in patients with newly diagnosed advanced cases and one in patients with recurrent cancer). The studies evaluated niraparib maintenance therapy compared with no maintenance therapy and used HRD testing to group patients according to HRD status. Compared to placebo, niraparib maintenance therapy improved progression-free survival in patients with newly diagnosed and recurrent ovarian cancer, and in tumours with HRD or HRP (GRADE: High), but the studies did not compare the results between the HRD and HRP groups. The frequency of adverse events was higher in the niraparib group. We identified no studies that evaluated the clinical utility of HRD testing.We conducted a primary economic evaluation to evaluate the cost-effectiveness of HRD testing for people with newly diagnosed ovarian cancer in an Ontario setting. Our analysis used a 5-year time horizon. HRD testing (for all eligible people or only for people with wild type) resulted in a lower proportion of patients receiving niraparib maintenance therapy, leading to lower costs and fewer quality-adjusted life-years (QALYs). The average total cost per patient was $131,375 for no HRD testing, $126,867 for HRD testing only in people with wild type, and $127,746 for HRD testing in all eligible people. The average total QALYs per patient were 2.087 for no HRD testing, 1.971 for HRD testing only in people with wild type, and 1.971 for HRD testing in all eligible people. Our budget impact analysis suggested that assuming a high uptake rate, publicly funding HRD testing for people with newly diagnosed ovarian cancer would lead to a total saving of $9.00 million (if HRD testing were funded for all) to $12.67 million (if HRD testing were funded for people with wild type) over the next 5 years. Publicly funding HRD testing for people with recurrent cancer would lead to a total saving of $16.31 million (if HRD testing were funded for all) to $21.67 million (if HRD testing were funded for people with wild type) over the next 5 years.We identified no studies that evaluated quantitative preferences for HRD testing. Based on two studies that evaluated patients and oncologists' preferences for maintenance therapy with a PARP inhibitor in the recurrent setting, a decrease in moderate to severe adverse events was more important for patients than an improvement in progression-free survival; however, improvement in progression-free survival was more important for oncologists. Both patients and oncologists accepted some trade-offs between efficacy and safety. The people with ovarian cancer we spoke with demonstrated a shared value for access to information, prevention of cancer recurrence, and overall survival with minimal adverse effects. This was consistent with findings from another survey in patients with ovarian cancer and at least one episode of recurrence, which suggest that patients prioritize treatment benefit over some treatment adverse events in the context of niraparib maintenance therapy. Interviewees also emphasized the importance of the patient-doctor partnership, access to local health care services, and patient education.
CONCLUSIONS
In patients with newly diagnosed (advanced) or recurrent high-grade serous or endometrioid ovarian cancer, niraparib maintenance therapy improved progression-free survival compared with no maintenance therapy in tumours with HRD or HRP (GRADE: High). Because we identified no studies on the clinical utility of HRD testing, we cannot comment on how it would affect patient decisions and clinical outcomes.Over a 5-year time horizon, HRD testing for people with wild type could save $4,509 per person and lead to a loss of 0.116 QALY. The findings of our economic analyses are dependent on assumptions about the use of niraparib following HRD testing. We estimate that publicly funding HRD testing would lead to a total saving of $9 million to $12.67 million for newly diagnosed cancer, and a total saving of $16.31 million to $21.67 million for recurrent cancer over 5 years, assuming the use of niraparib maintenance therapy would be reduced following HRD testing.Patients prioritized decreasing the risk of moderate to severe adverse events of maintenance therapy with PARP inhibitors over improving progression-free survival, and oncologists prioritized improving progression-free survival over decreasing the risk of moderate to severe adverse events. However, both patients and oncologists were open to accepting certain trade-offs between treatment efficacy and toxicity. The people we interviewed, who had lived experience with ovarian cancer and genetic testing, valued the potential clinical benefits of HRD testing for themselves and their family members. They emphasized patient education as an important consideration for public funding in Ontario.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Technology Assessment, Biomedical; Poly(ADP-ribose) Polymerase Inhibitors; Carcinoma, Endometrioid; Ovarian Neoplasms
PubMed: 37637244
DOI: No ID Found -
Frontiers in Endocrinology 2023Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer,... (Meta-Analysis)
Meta-Analysis
AIMS
Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer, combined with spironolactone, an antiandrogen medication, may exert complementary effects on PCOS. We therefore performed a meta-analysis of trials in which metformin combined with spironolactone was applied to treat PCOS to evaluate the efficacy and safety of the combination therapy.
METHODS
We retrieved the PubMed, Embase, Scopus, Cochrane Library, CNKI, CBM, Wangfang, and VIP databases for literatures published from their inception to December 16, 2022 on the effects of metformin combined with spironolactone in the treatment of PCOS. Inclusion criteria according to P.I.C.O.S criteria were: PCOS patients, metformin combined with spironolactone interventions, metformin alone control group, and randomized controlled trials with the following outcome data: body mass index (BMI), hirsutism score, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and side effects including nausea, vomiting, diarrhea and drug withdrawal.
RESULTS
Our results revealed that metformin combined with spironolactone significantly reduced BMI and TT, but that it exerted no significant effects on hirsutism score, or on FSH or LH concentrations. Combined treatment also resulted in a significant diminution in FBG and insulin resistance using the HOMA-IR when the interventional time was greater than 6 months. In addition, the combination did not have a higher occurrence of adverse reactions than metformin alone.
CONCLUSION
Compared with metformin alone, metformin combined with spironolactone therapy may be more effective in reducing BMI and serum androgen levels, but the combination showed no significant effect on the hirsutism score or gonadotropin hormone levels, and was not associated with an elevation in side-effects. Moreover, when the treatment course was greater than 6 months, combination therapy reduced FBG and improved insulin resistance more effectively than metformin alone. However, more research is needed to determine the most effective course of treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022355515.
Topics: Female; Humans; Hirsutism; Insulin Resistance; Polycystic Ovary Syndrome; Spironolactone; Drug-Related Side Effects and Adverse Reactions; Follicle Stimulating Hormone, Human; Luteinizing Hormone
PubMed: 37635987
DOI: 10.3389/fendo.2023.1223768 -
Genes Aug 2023Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs)...
Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) contribute to the occurrence of metformin side effects. The aim of the present study was to identify intronic genetic variants modifying the occurrence of metformin side effects and to replicate them in individuals with T2DM and in women with PCOS. We performed Next Generation Sequencing (Illumina Next Seq) of 115 SNPs in a discovery cohort of 120 metformin users and conducted a systematic literature review. Selected SNPs were analysed in two independent cohorts of individuals with either T2DM or PCOS, using 5'-3'exonucleaseassay. A total of 14 SNPs in the organic cation transporters (OCTs) showed associations with side effects in an unadjusted binary logistic regression model, with eight SNPs remaining significantly associated after appropriate adjustment in the discovery cohort. Five SNPs were confirmed in a combined analysis of both replication cohorts but showed different association patterns in subgroup analyses. In an unweighted polygenic risk score (PRS), the risk for metformin side effects increased with the number of risk alleles. Intronic SNPs in the OCT cluster contribute to the development of metformin side effects in individuals with T2DM and in women with PCOS and are therefore of interest for personalized therapy options.
Topics: Female; Humans; Polymorphism, Single Nucleotide; Metformin; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Introns; Membrane Transport Proteins; Polycystic Ovary Syndrome
PubMed: 37628660
DOI: 10.3390/genes14081609 -
Frontiers in Endocrinology 2023The aim of the study was to identify available polycystic ovary syndrome (PCOS) models of care (MoCs) and describe their characteristics and alignment with the...
INTRODUCTION
The aim of the study was to identify available polycystic ovary syndrome (PCOS) models of care (MoCs) and describe their characteristics and alignment with the international PCOS guideline.
METHODS
Ovid MEDLINE, All EBM, PsycINFO, Embase, and CINAHL were searched from inception until 11 July 2022. Any study with a description of a PCOS MoC was included. Non-evidence-based guidelines, abstracts, study protocols, and clinical trial registrations were excluded. We also excluded MoCs delivered in research settings to minimize care bias. Meta-analysis was not performed due to heterogeneity across MoCs. We describe and evaluate each MoC based on the recommendations made by the international evidence-based guideline for assessing and managing PCOS.
RESULTS
Of 3,671 articles, six articles describing five MoCs were included in our systematic review. All MoCs described a multidisciplinary approach, including an endocrinologist, dietitian, gynecologist, psychologist, dermatologist, etc. Three MoCs described all aspects of PCOS care aligned with the international guideline recommendations. These include providing education on long-term risks, lifestyle interventions, screening and management of emotional well-being, cardiometabolic diseases, and the dermatological and reproductive elements of PCOS. Three MoCs evaluated patients' and healthcare professionals' satisfaction, with generally positive findings. Only one MoC explored the impact of their service on patients' health outcomes and showed improvement in BMI.
CONCLUSION
There is limited literature describing PCOS MoCs in routine practice. Future research should explore developing cost-effective co-created multidisciplinary PCOS MoCs globally. This may be facilitated by the exchange of best practices between institutions with an established MoC and those who are interested in setting one up.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346539, identifier CRD42022346539.
Topics: Female; Humans; Developing Countries; Educational Status; Emotions; Endocrinologists; Polycystic Ovary Syndrome
PubMed: 37614710
DOI: 10.3389/fendo.2023.1217468 -
Complementary Therapies in Medicine Oct 2023Diminished ovarian reserve (DOR) refers to the decreased number and quality of oocytes in the ovary. Acupuncture and moxibustion has a certain effect on DOR; however,... (Review)
Review
OBJECTIVE
Diminished ovarian reserve (DOR) refers to the decreased number and quality of oocytes in the ovary. Acupuncture and moxibustion has a certain effect on DOR; however, the number of studies and reports of research evidence are limited. This study aimed to conduct a scoping review of the clinical research status of acupuncture and moxibustion for treating patients with DOR.
METHOD
PubMed, Cochrane Library, Excerpta Medica database, Allied and Complementary Medicine Database, Chinese Biological Medicine, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, and Wanfang database were searched from January 2010 to May 2022 using keywords and medical subject heading terms. After applying the inclusion and exclusion criteria, relevant studies were selected. Structured tables and descriptive charts were made to visually express research features by using Excel, Original, IBM SPSS Model 18.0, Adobe Illustrator and other software packages. Report quality was evaluated for Cochrane bias using Review Manager 5.3.
RESULTS
Overall, 851 studies were identified; of these, 90 met the inclusion criteria. The results extracted from these studies were classified into four categories: research characteristics, study type, acupuncture and moxibustion prescriptions, and efficacy observation.
CONCLUSIONS
The quality assessment of acupuncture and moxibustion for DOR is not ideal. Therefore, standardisation and normalisation should be strengthened, and high-quality evidence is needed to further demonstrate the effectiveness of this approach. Due to heterogeneity in DOR diagnosis, the observation index should be updated with reference to the latest research to improve efficacy evaluation.
Topics: Female; Humans; Acupuncture Therapy; Asian People; Medicine, East Asian Traditional; Moxibustion; Ovarian Reserve; Ovarian Diseases
PubMed: 37598724
DOI: 10.1016/j.ctim.2023.102973 -
Frontiers in Endocrinology 2023To evaluate the effect of vitamin D supplementation on pregnancy and ovulation in patients with polycystic ovary syndrome. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of vitamin D supplementation on pregnancy and ovulation in patients with polycystic ovary syndrome.
METHOD
We searched Pubmed, Medline (via Ovid, 1974 to 2020), EMBASE (via Ovid, 1974 to 2020), Cochrane Central Register of Controlled Trials (via Ovid), Web of Science, CNKI, WangFang and the Vip database from inception until April 2021. Two researchers independently screened articles, collected data and evaluated the quality, with Review manager 5.3 for meta-analysis.
RESULTS
Totally 20 randomized controlled studies with 1961 subjects were included. Meta analysis showed that pregnancy rate [RR=1.44 (1.28, 1.62), p<0.00,001], ovulation rate [RR=1.42 (1.14, 1.78), p=0.002] and matured oocytes rate [RR=1.08 (1.03, 1.13), p=0.002] of vitamin D supplementation group were significantly higher than those of control group. Meanwhile, early miscarriage rate [RR=0.44 (0.30, 0.66), p<0.00,001], androgen level [MD=-2.31 (-3.51, -1.11), p=0.0002], luteinizing hormone [MD=-1.47 (-2.57, -0.36), p=0.009], follicle stimulating hormone [MD=-0.15 (-0.24, -0.05), p=0.002], and premature delivery rate [RR=0.38, 95% CI (0.21, 0.70), p=0.002] were declined significantly than the controls. However, only one article suggested that the progesterone [MD=6.52 (4.52, 8.52), p<0.05] in the vitamin D intervention group was increased. There was no notable difference in the biochemical pregnancy rate [RR=0.95 (0.55, 1.63), p=0.84], gestational hypertension rate [RR=0.40, 95% CI (0.15, 1.11), p=0.08], gestational diabetes mellitus rate [RR=0.27, 95% CI (0.05, 1.39), p=0.11], fertilization rate [RR=1.05 (1.00, 1.10), p=0.04], cleavage rate [RR=1.03 (0.99, 1.06), p=0.17], high-quality embryo rate [RR=1.08 (0.98, 1.20), p=0.10], endometrial thickness [MD=0.10], 77 (-0.23, 1.77), p=0.13], estrogen level [MD=-0.34 (-1.55, 0.87), p=0.59], LH/FSH [MD=-0.14, 95% CI (-0.48, 0.20), p=1.00] and anti-Mullerian hormone [MD=-0.22 (-0.65, 0.21), p=0.32].
CONCLUSION
Vitamin D supplementation contribute to the higher pregnancy and ovulation rates, and lower androgen, LH, FSH and early miscarriage rates in women with PCOS, regardless of the use of ovulation induction drugs or assisted reproductive technologies. However, no significant improvement was observed in fertilization rate or cleavage rate. Due to the limitation in quality of involved studies, more high-quality RCTs are needed for further validation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021250284.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Androgens; Dietary Supplements; Follicle Stimulating Hormone, Human; Ovulation; Polycystic Ovary Syndrome; Vitamin D
PubMed: 37593349
DOI: 10.3389/fendo.2023.1148556 -
EClinicalMedicine Sep 2023Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy...
BACKGROUND
Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS.
METHODS
We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640.
FINDINGS
From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n = 961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens + lifestyle were superior to metformin + lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]: -1.59 [-3.06, -0.12], p = 0.03; = 74%), SHBG (7.70 nmol/l [0.75, 14.66], p = 0.03; = 0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97, -0.26], p = 0.03; = 0% and -1.12 [-1.44, -0.79], p < 0.0001, = 0%, respectively), but were not superior to placebo + lifestyle for hirsutism (-0.93, [-3.37, 1.51], p = 0.45; = 76%) or SHBG (9.72 nmol/l [-0.71, 20.14], p = 0.07; = 31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58, -2.39], p < 0.0001, = 1%), and resulted in lower androstenedione levels (-0.30 ng/ml [-0.50, -0.10], p = 0.004; = 0%). Combination treatment with anti-androgens + metformin + lifestyle resulted in lower testosterone compared with metformin + lifestyle (-0.29 nmol/l [-0.52, -0.06], p = 0.01; = 61%), but there were no differences in hirsutism when anti-androgens + metformin + lifestyle were compared with either anti-androgens + lifestyle or metformin + lifestyle. In limited meta-analyses (n = 2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP ± placebo, with no differences in other outcomes.
INTERPRETATION
Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics.
FUNDING
National Health and Medical Research Council (NHMRC) of Australia Monash University.
PubMed: 37583655
DOI: 10.1016/j.eclinm.2023.102162 -
Cureus Jul 2023Polycystic ovarian syndrome (PCOS) is a widespread, complex, and multi-system hormonal disorder that occurs in women of reproductive age. The wide variation in practice... (Review)
Review
Polycystic ovarian syndrome (PCOS) is a widespread, complex, and multi-system hormonal disorder that occurs in women of reproductive age. The wide variation in practice in the treatment of PCOS is a direct consequence of the lack of sufficient evidence on alternative treatment strategies, as well as a poor understanding of the disorder itself. The aim of our systematic review was to assess the therapeutic advantages and adverse effects of metformin (MET), a standard treatment modality, with myoinositol (MI), a recent substitute that may be used alone or in combination with other remedies to treat PCOS. A literature search was done using PubMed Central, PubMed, Medline, Cochrane, Science Direct, and Google Scholar. Studies were limited to those published in English between 2012 and 2022 that focused on the management of PCOS with both MET and MI. The systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Using standard quality assessment tools, two reviewers independently assessed the content of the incorporated studies. Three meta-analyses, eight randomized controlled trials (RCTs), and one non-randomized non-controlled trial (NN-RCT) were deemed eligible. Following extensive analysis, we found that MET and MI are comparable in their effects on clinical, hormonal, and biochemical profiles. MI, however, had a better safety profile and tolerance due to minimal side effects compared to MET. These results demonstrate the potential role of MI as a novel asset in the armamentarium in the management of PCOS.
PubMed: 37575860
DOI: 10.7759/cureus.41748 -
Cancers Jul 2023Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare aggressive ovarian malignancy mainly affecting children, adolescents, and young adults. Since... (Review)
Review
BACKGROUND
Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare aggressive ovarian malignancy mainly affecting children, adolescents, and young adults. Since the discovery of mutations in the SMARCA4 gene in 2014, SCCOHT has become the subject of extensive investigation. However, international uniform treatment guidelines for SCCOHT are lacking and the outcome remains poor. The aim of this systematic review is to generate an overview of all reported patients with SCCOHT from 1990 onwards, describing the clinical presentation, genetic characteristics, treatment, and outcome.
METHODS
A systematic search was performed in the databases Embase, Medline, Web of Science, and Cochrane for studies that focus on SCCOHT. Patient characteristics and treatment data were extracted from the included studies. Survival was estimated using Kaplan-Meier's methodology. To assess the difference between survival, the log-rank test was used. To quantify the effect of the FIGO stage, the Cox proportional hazard regression model was estimated. The chi-squared test was used to study the association between the FIGO stage and the surgical procedures.
RESULTS
Sixty-seven studies describing a total of 306 patients were included. The median patient age was 25 years (range 1-60 years). The patients mostly presented with non-specific symptoms such as abdominal pain and sometimes showed hypercalcemia and elevated CA-125. A great diversity in the diagnostic work-up and therapeutic approaches was reported. The chemotherapy regimens were very diverse, all containing a platinum-based (cisplatin or carboplatin) backbone. Survival was strongly associated with the FIGO stage at diagnosis.
CONCLUSIONS
SCCOHT is a rare and aggressive ovarian cancer, with a poor prognosis, and information on adequate treatment for this cancer is lacking. The testing of mutations in SMARCA4 is crucial for an accurate diagnosis and may lead to new treatment options. Harmonization and international collaboration to obtain high-quality data on diagnostic investigations, treatment, and outcome are warranted to be able to develop international treatment guidelines to improve the survival chances of young women with SCCOHT.
PubMed: 37568608
DOI: 10.3390/cancers15153794 -
BMC Medicine Aug 2023The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women.
METHODS
Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed.
RESULTS
Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria.
CONCLUSIONS
Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk.
TRIAL REGISTRATION
PROSPERO registration: CRD42021285206, May 22, 2023.
Topics: Humans; Female; Gastrointestinal Microbiome; Polycystic Ovary Syndrome; Dysbiosis; Phylogeny; Microbiota
PubMed: 37559119
DOI: 10.1186/s12916-023-02975-8