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Cells May 2023Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been... (Review)
Review
Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE.
Topics: Humans; Female; Endometriosis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Neovascularization, Pathologic; Endometrium
PubMed: 37174718
DOI: 10.3390/cells12091318 -
Advances in Therapy Nov 2022Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy between drugs remains unknown.
METHODS
We identified studies by searching the MEDLINE, Cochrane Library, and ICHUSHI databases and included randomized controlled trials (RCTs) that used total dysmenorrhea score and visual analogue scale (VAS) as outcome measures to evaluate LEPs and progestins for primary and secondary dysmenorrhea. We analyzed results by meta-analysis and network meta-analysis (NMA).
RESULTS
We identified 10 articles on eight RCTs and included seven drugs (six LEPs and one progestin, i.e., dienogest) and placebo in the analysis. Meta-analysis showed improvements in total dysmenorrhea score and VAS for almost all drugs compared with placebo. In NMA, VAS in secondary dysmenorrhea improved more with dienogest than with norethisterone/ethinylestradiol (mean difference - 25.84 [95% CrI - 44.46 to - 7.15]). In the comparison of administration regimens, VAS improved more with progestin-continuous than LEP-cyclic and the surface under the cumulative ranking (SUCRA) of LEP-extended and progestin-continuous appeared to be higher than that of LEP-cyclic.
CONCLUSIONS
We confirmed that LEPs and dienogest are effective for primary and secondary dysmenorrhea and suggest that continuous regimens may be more effective than cyclic regimens in improving outcomes.
Topics: Dysmenorrhea; Estrogens; Female; Gastrointestinal Diseases; Humans; Japan; Network Meta-Analysis; Norethindrone; Progestins
PubMed: 36048405
DOI: 10.1007/s12325-022-02298-9 -
The Journal of Sexual Medicine Dec 2022Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual... (Review)
Review
Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning; A Systematic Literature Review.
BACKGROUND
Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual symptoms.
AIMS
To systematically review and meta-analyze the effect of systemic hormone replacement therapy (sHRT) on psychological well-being and sexual functioning in women after surgical menopause and BSO.
METHODS
Medline/Pubmed, EMBASE and PsychInfo were systematically searched until November 2021. Randomized controlled trials investigating the effect of sHRT on psychological well-being and/or sexual functioning in surgically menopausal women and women after BSO were eligible for inclusion. Two independent authors performed study selection, risk of bias assessment and data extraction. Standardized mean differences (SMDs) were calculated.
OUTCOMES
Primary outcomes for psychological well-being were defined as overall psychological well-being, depression, and anxiety. Primary outcomes for sexual functioning were defined as overall sexual functioning, sexual desire, and sexual satisfaction. All outcomes were assessed on short (≤12 weeks) or medium term (13-26 weeks).
RESULTS
Twelve studies were included. Estradiol had a beneficial effect on depressed mood on short term 3-6 years after surgery or 2 years (median) after surgery with high heterogeneity (SMD: -1.37, 95%CI: -2.38 to -0.37, P = .007, I 79%). Testosterone had a beneficial effect on overall sexual functioning on short to medium term 4.6 years (mean) after surgery (SMD 0.38, 95%CI 0.11-0.65, I 0%) and on sexual desire on medium term at least 3-12 months after surgery (SMD 0.38, 95%CI 0.19-0.56, I 54%). For most studies, risk of bias was uncertain.
CLINICAL IMPLICATIONS
Estradiol may beneficially affect psychological symptoms after surgical menopause or BSO and testosterone might improve sexual desire and overall sexual functioning.
STRENGTHS AND LIMITATIONS
This review only included patient-reported outcomes, thereby reflected perceived and not simply objective symptoms in surgically menopausal women and women after BSO. The small number of studies highly varied in nature and bias could not be excluded, therefore our results should be interpreted with great caution.
CONCLUSION
Independent randomized controlled clinical trials investigating the effects of estrogen-progesterone and testosterone on psychological and sexual symptoms after surgical menopause are needed.
PROSPERO REGISTRATION NUMBER
CRD42019136698. Stuursma A, Lanjouw L, Idema DL, et al. Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning: A Systematic Literature Review. J Sex Med 2022;19:1778-1789.
Topics: Humans; Female; Progesterone; Quality of Life; Hormone Replacement Therapy; Menopause; Ovariectomy; Estrogens; Testosterone; Estradiol
PubMed: 36175351
DOI: 10.1016/j.jsxm.2022.08.191 -
JAMA Nov 2022It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.
Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
IMPORTANCE
It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.
OBJECTIVE
To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.
DATA SOURCES
PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022.
STUDY SELECTION
English-language randomized clinical trials and prospective cohort studies of fair or good quality.
DATA EXTRACTION AND SYNTHESIS
Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.
MAIN OUTCOMES AND MEASURES
Morbidity and mortality related to chronic conditions; health-related quality of life.
RESULTS
Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year.
CONCLUSIONS AND RELEVANCE
Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.
Topics: Female; Humans; Advisory Committees; Chronic Disease; Estrogens; Fractures, Bone; Hormone Replacement Therapy; Hormones; Postmenopause; Primary Prevention; Progestins; Prospective Studies; Quality of Life; Risk Assessment; United States; Urinary Incontinence; Venous Thromboembolism
PubMed: 36318128
DOI: 10.1001/jama.2022.18324 -
Frontiers in Endocrinology 2023To determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished ovarian reserve (DOR) than clomiphene citrate (CC)/letrozole... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished ovarian reserve (DOR) than clomiphene citrate (CC)/letrozole (LE) plus gonadotropin in IVF or ICSI treatment.
METHODS
Nine databases were searched until May 24, 2023, to identify relevant studies. Forest plots were used to present the results of this meta-analysis. Begg's and Egger's tests were applied to estimate publication bias. Subgroup and sensitivity analysis were performed to check the potential sources of heterogeneity and verify the robustness of the pooled results, respectively.
RESULTS
A total of 14 studies with 4182 participants were included for meta-analysis. There was evidence of a statistically notable increase in clinical pregnancy rate (OR = 1.39, 95%CI [1.01, 1.91], = 0.05), optimal embryos rate (OR = 1.50, 95%CI [1.20, 1.88], = 0.0004), and cumulative pregnancy rate (OR = 1.73, 95%CI [1.14, 2.60], = 0.009), the duration and the amount of gonadotropin required (MD = 1.56, 95%CI [0.47, 2.66], = 0.005; SMD = 1.51, 95%CI [0.90, 2.12], < 0.00001), along with decrease cycle cancellation rate (OR = 0.78, 95%CI [0.64, 0.95], = 0.02), luteinizing hormone (LH) level on the day of hCG (SMD = -0.81, 95%CI [-1.10, -0.53], < 0.00001), and premature LH surge rate (OR = 0.10, 95%CI [0.07, 0.15], < 0.00001) when PPOS was used. No evidence for publication bias within results was revealed.
CONCLUSIONS
Based on evidence-based results, PPOS protocol seems to improve IVF/ICSI outcomes for women with DOR. More research with larger sample sizes and rigorous designs are required to further explore the value of PPOS among women diagnosed with DOR.
SYSTEMATIC REVIEW REGISTRATION
www.crd.york.ac.uk, identifier CRD42023430202.
Topics: Female; Humans; Pregnancy; Ovarian Diseases; Ovarian Reserve; Ovulation Induction; Progestins; Sperm Injections, Intracytoplasmic; Steroids; Clinical Protocols
PubMed: 37670890
DOI: 10.3389/fendo.2023.1232935 -
Reviews in Endocrine & Metabolic... Apr 2023Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity... (Review)
Review
Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Leptin; C-Reactive Protein; Obesity, Maternal; Adiponectin; Progesterone; Obesity; Biomarkers; Insulin; Chorionic Gonadotropin; Carbon
PubMed: 36520252
DOI: 10.1007/s11154-022-09762-5 -
Frontiers in Endocrinology 2024Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial.
METHODS
We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants.
RESULTS
Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; =0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; =0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life ( = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT.
DISCUSSION
These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.
Topics: Female; Humans; Cognition; Estrogen Replacement Therapy; Estrogens; Hormone Replacement Therapy; Progestins
PubMed: 38501109
DOI: 10.3389/fendo.2024.1350318 -
The Cochrane Database of Systematic... Oct 2022Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic... (Review)
Review
BACKGROUND
Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic hypogonadism, characterised by amenorrhoea or oligomenorrhoea, with low ovarian sex hormones (oestrogen deficiency) and elevated pituitary gonadotrophins. POI with primary amenorrhoea may occur as a result of chromosomal and genetic abnormalities, such as Turner syndrome, Fragile X, or autosomal gene defects; secondary amenorrhoea may be iatrogenic after the surgical removal of the ovaries, radiotherapy, or chemotherapy. Other causes include autoimmune diseases, viral infections, and environmental factors; in most cases, POI is idiopathic. Appropriate replacement of sex hormones in women with POI may facilitate the achievement of near normal uterine development. However, the optimal effective hormone therapy (HT) regimen to maximise the reproductive potential for women with POI remains unclear.
OBJECTIVES
To investigate the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in September 2021. We also checked references of included studies, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the effect of various hormonal preparations on the uterine development of women diagnosed with POI.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcome was uterine volume; secondary outcomes were endometrial thickness, endometrial histology, uterine perfusion, reproductive outcomes, and any reported adverse events.
MAIN RESULTS
We included three studies (52 participants analysed in total) investigating the role of various hormonal preparations in three different contexts, which deemed meta-analysis unfeasible. We found very low-certainty evidence; the main limitation was very serious imprecision due to small sample size. Conjugated oral oestrogens versus transdermal 17ß-oestradiol We are uncertain of the effect of conjugated oral oestrogens compared to transdermal 17ß-oestradiol (mean difference (MD) -18.2 (mL), 95% confidence interval (CI) -23.18 to -13.22; 1 RCT, N = 12; very low-certainty evidence) on uterine volume, measured after 12 months of treatment. The study reported no other relevant outcomes (including adverse events). Low versus high 17ß-oestradiol dose We are uncertain of the effect of a lower dose of 17ß-oestradiol compared to a higher dose of 17ß-oestradiol on uterine volume after three or five years of treatment, or adverse events (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes. Oral versus vaginal administration of oestradiol and dydrogesterone We are uncertain of the effect of an oral or vaginal administration route on uterine volume and endometrial thickness after 14 or 21 days of administration (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes (including adverse events).
AUTHORS' CONCLUSIONS
No clear conclusions can be drawn in this systematic review, due to the very low-certainty of the evidence. There is a need for pragmatic, well designed, randomised controlled trials, with adequate power to detect differences between various HT regimens on uterine growth, endometrial development, and pregnancy outcomes following the transfer of donated gametes or embryos in women diagnosed with POI.
Topics: Amenorrhea; Dydrogesterone; Endometrium; Estradiol; Estrogens; Female; Humans; Menopause, Premature; Pregnancy
PubMed: 36200708
DOI: 10.1002/14651858.CD008209.pub2 -
The Cochrane Database of Systematic... Dec 2022Preterm birth (PTB), defined as birth prior to 37 weeks of gestation, occurs in ten percent of all pregnancies. PTB is responsible for more than half of neonatal and... (Review)
Review
BACKGROUND
Preterm birth (PTB), defined as birth prior to 37 weeks of gestation, occurs in ten percent of all pregnancies. PTB is responsible for more than half of neonatal and infant mortalities and morbidities. Because cervical insufficiency is a common cause of PTB, one possible preventive strategy involves insertion of a cervical pessary to support the cervix. Several published studies have compared the use of pessary with different management options and obtained questionable results. This highlights the need for an up-to-date systematic review of the evidence.
OBJECTIVES
To evaluate the benefits and harms of cervical pessary for preventing preterm birth in women with singleton pregnancies and risk factors for cervical insufficiency compared to no treatment, vaginal progesterone, cervical cerclage or bedrest.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform to 22 September 2021. We also searched the reference lists of included studies for additional records.
SELECTION CRITERIA
We included published and unpublished randomised controlled trials (RCTs) comparing cervical pessary with no treatment, vaginal progesterone, cervical cerclage or bedrest for preventing PTB. We excluded quasi-randomised trials. Our primary outcome was delivery before 34 weeks' gestation. Our secondary outcomes were 1. delivery before 37 weeks' gestation, 2. maternal mortality, 3. maternal infection or inflammation, 4. preterm prelabour rupture of membranes, 5. harm to woman from the intervention, 6. maternal medications, 7. discontinuation of the intervention, 8. maternal satisfaction, 9. neonatal/paediatric care unit admission, 10. fetal/infant mortality, 11. neonatal sepsis, 12. gestational age at birth, 13. harm to offspring from the intervention 14. birthweight, 15. early neurodevelopmental morbidity, 15. late neurodevelopmental morbidity, 16. gastrointestinal morbidity and 17. respiratory morbidity.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and risk of bias, evaluated trustworthiness based on criteria developed by the Cochrane Pregnancy and Childbirth Review Group, extracted data, checked for accuracy and assessed certainty of evidence using the GRADE approach.
MAIN RESULTS
We included eight RCTs (2983 participants). We included five RCTs (1830 women) in the comparison cervical pessary versus no treatment, three RCTs (1126 pregnant women) in the comparison cervical pessary versus vaginal progesterone, and one study (13 participants) in the comparison cervical pessary versus cervical cerclage. Overall, the certainty of evidence was low to moderate due to inconsistency (statistical heterogeneity), imprecision (few events and wide 95% confidence intervals (CIs) consistent with possible benefit and harm), and risk of performance and detection bias. Cervical pessary versus no treatment Cervical pessary compared with no treatment may reduce the risk of delivery before 34 weeks (risk ratio (RR) 0.72, 95% CI 0.33 to 1.55; 5 studies, 1830 women; low-certainty evidence) or before 37 weeks (RR 0.68, 95% CI 0.44 to 1.05; 5 studies, 1830 women; low-certainty evidence). However, these results should be viewed with caution because the 95% CIs cross the line of no effect. Cervical pessary compared with no treatment probably has little or no effect on the risk of maternal infection or inflammation (RR 1.04, 95% CI 0.87 to 1.26; 2 studies, 1032 women; moderate-certainty evidence). It is unclear if cervical pessary compared with no treatment has an effect on neonatal/paediatric care unit admission (RR 0.96, 95% CI 0.58 to 1.59; 3 studies, 1332 infants; low-certainty evidence) or fetal/neonatal mortality (RR 0.93, 95% CI 0.58 to 1.48; 5 studies, 1830 infants; low-certainty evidence) because the 95% CIs are compatible with a wide range of effects that encompass both appreciable benefit and harm. Cervical pessary versus vaginal progesterone Cervical pessary may reduce the risk of delivery before 34 weeks (RR 0.72, 95% CI 0.52 to 1.02; 3 studies, 1126 women; moderate-certainty evidence) or before 37 weeks (RR 0.89, 95% CI 0.73 to 1.09; 3 studies, 1126 women; moderate-certainty evidence), but we are uncertain of the results because the 95% CI crosses the line of no effect. The intervention probably has little or no effect on maternal infection or inflammation (RR 0.95, 95% CI 0.81 to 1.12; 2 studies, 265 women; moderate-certainty evidence). It is unclear if cervical pessary compared with vaginal progesterone has an effect on the risk of neonatal/paediatric care unit admission (RR 0.98, 95% CI 0.49 to 1.98; low-certainty evidence) or fetal/neonatal mortality (RR 1.97, 95% CI 0.50 to 7.70; 2 studies; 265 infants; low-certainty evidence) because the 95% CIs are compatible with a wide range of effects that encompass both appreciable benefit and harm. Cervical pessary versus cervical cerclage Only one very small study of 13 pregnant women contributed data to this comparison; the results were unclear.
AUTHORS' CONCLUSIONS
In women with a singleton pregnancy, cervical pessary compared with no treatment or vaginal progesterone may reduce the risk of delivery before 34 weeks or 37 weeks, although these results should be viewed with caution due to uncertainty around the effect estimates. There is insufficient evidence with regard to the effect of cervical pessary compared with cervical cerclage on PTB. Due to low certainty-evidence in many of the prespecified outcomes and non-reporting of several other outcomes of interest for this review, there is a need for further robust RCTs that use standardised terminology for maternal and offspring outcomes. Future trials should take place in a range of settings to improve generalisability of the evidence. Further research should concentrate on comparisons of cervical pessary versus cervical cerclage and bed rest. Investigation of different phenotypes of PTB may be relevant.
Topics: Female; Pregnancy; Humans; Pessaries; Cervix Uteri; Progesterone; Premature Birth; Cerclage, Cervical
PubMed: 36453699
DOI: 10.1002/14651858.CD014508 -
BMC Women's Health Jan 2024Menopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Menopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for the cardiovascular system of postmenopausal women are not very clear.
OBJECTIVES
To evaluate cardiovascular benefits and risks of MHT in postmenopausal women, and analyze the underlying factors that affect both.
SEARCH STRATEGY
The EMBASE, MEDLINE, and CENTRAL databases were searched from 1975 to July 2022.
SELECTION CRITERIA
Randomized Clinical Trials (RCTs) that met pre-specified inclusion criteria were included.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data independently. A meta-analysis of random effects was used to analyze data.
MAIN RESULTS
This systematic review identified 33 RCTs using MHT involving 44,639 postmenopausal women with a mean age of 60.3 (range 48 to 72 years). There was no significant difference between MHT and placebo (or no treatment) in all-cause death (RR = 0.96, 95%CI 0.85 to 1.09, I = 14%) and cardiovascular events (RR = 0.97, 95%CI 0.82 to 1.14, I = 38%) in the overall population of postmenopausal women. However, MHT would increase the risk of stroke (RR = 1.23, 95%CI 1.08 to 1.41,I = 0%) and venous thromboembolism (RR = 1.86, 95%CI 1.39 to 2.50, I = 24%). Compared with placebo, MHT could improve flow-mediated arterial dilation (FMD) (SMD = 1.46, 95%CI 0.86 to 2.07, I = 90%), but it did not improve nitroglycerin-mediated arterial dilation (NMD) (SMD = 0.27, 95%CI - 0.08 to 0.62, I = 76%). Compared with women started MHT more than 10 years after menopause, women started MHT within 10 years after menopause had lower frequency of all-cause death (P = 0.02) and cardiovascular events (P = 0.002), and more significant improvement in FMD (P = 0.0003). Compared to mono-estrogen therapy, the combination therapy of estrogen and progesterone would not alter the outcomes of endpoint event. (all-cause death P = 0.52, cardiovascular events P = 0.90, stroke P = 0.85, venous thromboembolism P = 0.33, FMD P = 0.46, NMD P = 0.27).
CONCLUSIONS
MHT improves flow-mediated arterial dilation (FMD) but fails to lower the risk of all-cause death and cardiovascular events, and increases the risk of stroke and venous thrombosis in postmenopausal women. Early acceptance of MHT not only reduces the risk of all-cause death and cardiovascular events but also further improves FMD, although the risk of stroke and venous thrombosis is not reduced. There is no difference in the outcome of cardiovascular system endpoints between mono-estrogen therapy and combination therapy of estrogen and progesterone.
Topics: Female; Humans; Middle Aged; Aged; Venous Thromboembolism; Postmenopause; Progesterone; Arteries; Stroke; Estrogens; Hormone Replacement Therapy; Venous Thrombosis; Risk Assessment
PubMed: 38263123
DOI: 10.1186/s12905-023-02788-0