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International Journal of Hyperthermia :... 2021To evaluate the clinical effects of image-guided thermal ablation for the treatment of symptomatic adenomyosis (AD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the clinical effects of image-guided thermal ablation for the treatment of symptomatic adenomyosis (AD).
DATA SOURCES
We searched PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov and Google Scholar for literature from January 2000 to September 2020.
METHODS OF STUDY SELECTION
We included all studies reporting clinical outcomes of image-guided thermal ablation for AD, involving high-intensity focused ultrasound (HIFU), percutaneous microwave ablation (PMWA) and radiofrequency ablation (RFA). Two independent researchers performed study selection according to the screening criteria.
RESULTS
A total of 38 studies representing 15,908 women were included. Compared with those at baseline, the visual analog scale scores, the symptom severity scores and the menorrhagia severity scores decreased significantly after these thermal ablation therapies. The mean ablation time was 92.18 min, 24.15 min and 31.93 min during HIFU, PMWA and RFA, respectively. The non-perfused volume ratio of AD was 68.3% for HIFU, 82.5% for PMWA and 79.2% for RFA. The reduction rates of uterine volume were 33.6% (HIFU), 46.8% (PMWA) and 44.0% (RFA). The reduction rates of AD volume were 45.1% (HIFU), 74.9% (PMWA) and 61.3% (RFA). The relief rates of dysmenorrhea were 84.2% (HIFU), 89.7% (PMWA) and 89.2% (RFA). The incidence of minor adverse events was 39.0% (HIFU), 51.3% (PMWA) and 3.6% (RFA). The re-intervention rates were 4.0% (HIFU) and 28.7% (RFA). The recurrence rate was 10.2% after HIFU. The pregnancy rates were 16.7% (HIFU), 4.93% (PMWA) and 35.8% (RFA).
CONCLUSION
Image-guided HIFU, PMWA and RFA may be effective and safe minimally invasive therapies for symptomatic AD.
Topics: Adenomyosis; Dysmenorrhea; Female; High-Intensity Focused Ultrasound Ablation; Humans; Menorrhagia; Pregnancy; Radiofrequency Ablation; Treatment Outcome
PubMed: 34139945
DOI: 10.1080/02656736.2021.1939443 -
The Cochrane Database of Systematic... Feb 2021Heavy menstrual bleeding (HMB) is common in otherwise healthy women of reproductive age, and can affect physical health and quality of life. Surgery is usually a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heavy menstrual bleeding (HMB) is common in otherwise healthy women of reproductive age, and can affect physical health and quality of life. Surgery is usually a second-line treatment of HMB. Endometrial resection/ablation (EA/ER) to remove or ablate the endometrium is less invasive than hysterectomy. Hysterectomy is the definitive treatment and can be via open (laparotomy) approach, or via minimally invasive approaches (vaginally or laparoscopically). Each approach has its own advantages and risk profile.
OBJECTIVES
To compare the effectiveness, acceptability and safety of endometrial resection or ablation versus different routes of hysterectomy (open, minimally invasive hysterectomy, or unspecified route) for the treatment of HMB.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase and PsycINFO (July 2020), and reference lists, grey literature and trial registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compared techniques of endometrial resection/ablation with hysterectomy (by any technique) for the treatment of HMB in premenopausal women.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 10 RCTs (1966 participants) comparing EA/ER to hysterectomy (open (abdominal), minimally invasive (laparoscopic or vaginal), or unspecified (or at surgeon's discretion) route of hysterectomy). The results were rated as moderate-, low- and very low-certainty evidence. Endometrial resection/ablation versus open hysterectomy We found two trials. Women having EA/ER are probably less likely to perceive an improvement in HMB compared to women having open hysterectomy (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.95; 2 studies, 247 women; moderate-certainty evidence) and probably have a 13% risk of requiring further surgery for treatment failure (compared to 0 on the open hysterectomy group; 2 studies, 247 women; moderate-certainty evidence). Both treatments probably lead to similar quality of life at two years (mean difference (MD) -5.30, 95% CI -11.90 to 1.30; 1 study, 155 women; moderate-certainty evidence) and satisfaction rate at one year (RR 0.91, 95% CI 0.82 to 1.00; 1 study, 194 women; moderate-certainty evidence). There may be no difference in serious adverse events (RR 1.29, 95% CI 0.32 to 5.20; 2 studies, 247 women; low-certainty evidence). EA/ER probably reduces time to return to normal activity compared to open hysterectomy (MD -21.00 days, 95% CI -24.78 to -17.22; 1 study, 197 women; moderate-certainty evidence). Endometrial resection/ablation versus minimally invasive hysterectomy We found five trials. The proportion of women with perception of improvement in HMB at two years may be similar between groups (RR 0.97, 95% CI 0.90 to 1.04; 1 study, 79 women; low-certainty evidence). Blood loss may be higher in the EA/ER group when assessed using the Pictorial Blood Assessment Chart (MD 44.00, 95% CI 36.09 to 51.91; 1 study, 68 women; low-certainty evidence). Quality of life is probably lower in the EA/ER group compared to the minimally invasive hysterectomy group at two years according to the 36-item Short Form (SF-36) (MD -10.71, 95% CI -15.11 to -6.30; 2 studies, 145 women; moderate-certainty evidence) and Menorrhagia Multi-Attribute Scale (RR 0.82, 95% CI 0.70 to 0.95; 1 study, 616 women; moderate-certainty evidence). EA/ER probably increases the risk of further surgery for HMB compared to minimally invasive hysterectomy (RR 7.70, 95% CI 2.54 to 23.32; 4 studies, 922 women; moderate-certainty evidence) and treatments probably have similar rates of any serious adverse events (RR 0.75, 95% CI 0.35 to 1.59; 4 studies, 809 women; moderate-certainty evidence). Women with EA/ER are probably less likely to be satisfied with treatment at one year (RR 0.90, 95% CI 0.85 to 0.94; 1 study, 558 women; moderate-certainty evidence). We were unable to pool data for time to return to work or normal life because of extreme heterogeneity (99%); however, the three studies reporting this all had the same direction of effect favouring EA/ER. Endometrial resection/ablation versus unspecified route of hysterectomy We found three trials. EA/ER may lead to a lower perception of improvement in HMB compared to unspecified route of hysterectomy (RR 0.89, 95% CI 0.83 to 0.95; 2 studies, 403 women; low-certainty evidence). Although EA/ER may lead to similar quality of life using the SF-36 General Health Perception at two years' follow-up (MD -1.90, 95% CI -8.67 to 4.87; 1 study, 209 women; low-certainty evidence), the proportion of women with improvement in general health at one year may be lower (RR 0.85, 95% CI 0.77 to 0.95; 1 study, 185 women; low-certainty evidence). EA/ER probably has a risk of 5.4% of requiring further surgery for treatment failure (compared to 0 with total hysterectomy; 2 studies, 374 women; moderate-certainty evidence) and reduces the proportion of women with any serious adverse event (RR 0.21, 95% CI 0.06 to 0.80; 2 studies, 374 women; moderate-certainty evidence). Both treatments probably lead to a similar satisfaction rate at one year' follow-up (RR 0.96, 95% CI 0.88 to 1.04; 3 studies, 545 women; moderate-certainty evidence). EA/ER may lead to shorter time to return to normal activity (MD -18.90 days, 95% CI -24.63 to -13.17; 1 study, 172 women; low-certainty evidence).
AUTHORS' CONCLUSIONS
Endometrial resection/ablation (EA/ER) offers an alternative to hysterectomy as a surgical treatment for HMB. Effectiveness varies with EA/ER compared to different hysterectomy approaches. The perception of improvement in HMB with EA/ER is probably lower compared to open and unspecified route of hysterectomy, but may be similar compared to minimally invasive. Quality of life with EA/ER is probably similar to open and unspecified route of hysterectomy, but lower compared to minimally invasive hysterectomy. Further surgery for treatment failure is probably more likely with EA/ER compared to all routes of hysterectomy. Satisfaction rates also vary. EA/ER probably has a similar rate of satisfaction compared to open and unspecified route of hysterectomy, but a lower rate of satisfaction compared to minimally invasive hysterectomy. The proportion having any serious adverse event appears similar in all groups, but specific adverse events did reported difference between EA/ER and different routes. We were unable to draw conclusions about the time to return to normal activity, but the direction of effect suggests it is likely to be shorter with EA/ER.
Topics: Bias; Endometrial Ablation Techniques; Endometrium; Female; Humans; Hysterectomy; Hysteroscopy; Menorrhagia; Minimally Invasive Surgical Procedures; Operative Time; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33619722
DOI: 10.1002/14651858.CD000329.pub4 -
The Cochrane Database of Systematic... Sep 2020Plasmodium vivax malaria has a persistent liver stage that causes relapse of the disease and continued P vivax transmission. Primaquine (PQ) is used to clear the liver... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plasmodium vivax malaria has a persistent liver stage that causes relapse of the disease and continued P vivax transmission. Primaquine (PQ) is used to clear the liver stage of the parasite, but treatment is required for 14 days. Primaquine also causes haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Tafenoquine (TQ) is a new alternative to PQ with a longer half-life and can be used as a single-dose treatment.
OBJECTIVES
To assess the effects of tafenoquine 300 mg (single dose) on preventing P vivax relapse.
SEARCH METHODS
We searched the following up to 3 June 2020: the Cochrane Infectious Diseases Group Specialized Register; CENTRAL; MEDLINE; Embase; and three other databases. We also searched the WHO International Clinical Trial Registry Platform and the metaRegister of Controlled Trials for ongoing trials using "tafenoquine" and "malaria" as search terms up to 3 June 2020.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that gave TQ to prevent relapse in people with P vivax malaria. We planned to include trials irrespective of whether participants had been screened for G6PD enzyme deficiency.
DATA COLLECTION AND ANALYSIS
All review authors independently extracted data and assessed risk of bias. As true relapse and reinfection are difficult to differentiate in people living in endemic areas, studies report "recurrences" of infection as a proxy for relapse. We carried out meta-analysis where appropriate, and gave estimates as risk ratios (RR) with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
Three individually randomized RCTs met our inclusion criteria, all in endemic areas, and thus reporting recurrence. Trials compared TQ with PQ or placebo, and all participants received chloroquine (CQ) to treat the asexual infection). In all trials, pregnant and G6PD-deficient people were excluded. Tafenoquine 300 mg single dose versus no treatment for relapse prevention Two trials assessed this comparison. TQ 300 mg single dose reduces P vivax recurrences compared to no antihypnozoite treatment during a six-month follow-up, but there is moderate uncertainty around effect size (RR 0.32, 95% CI 0.12 to 0.88; 2 trials, 504 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (2 trials, 504 participants; moderate-certainty evidence). However, we are uncertain if TQ causes more serious adverse events (2 trials, 504 participants; very low-certainty evidence). Both RCTs reported a total of 23 serious adverse events in TQ groups (One RCT reported 21 events) and a majority (15 events) were a drop in haemoglobin level by > 3g/dl (or >30% reduction from baseline). Tafenoquine 300 mg single dose versus primaquine 15 mg/day for 14 days for relapse prevention Three trials assessed this comparison. There is probably little or no difference between TQ and PQ in preventing recurrences (proxy measure for relapse) up to six months of follow-up (RR 1.04, 95% CI 0.8 to 1.34; 3 trials, 747 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (3 trials, 747 participants; moderate-certainty evidence). We are uncertain if TQ can cause more serious adverse events compared to PQ (3 trials, 747 participants; very low-certainty evidence). Two trials had higher point estimates against TQ while the other showed the reverse. Most commonly reported serious adverse event in TQ group was a decline in haemoglobin level (19 out of 29 events). Some other serious adverse events, though observed in the TQ group, are unlikely to be caused by it (Hepatitis E infection, limb abscess, pneumonia, menorrhagia).
AUTHORS' CONCLUSIONS
TQ 300 mg single dose prevents relapses after clinically parasitologically confirmed P vivax malaria compared to no antihypnozoite treatment, and with no difference detected in studies comparing it to PQ to date. However, the inability to differentiate a true relapse from a recurrence in the available studies may affect these estimates. The drug is untested in children and in people with G6PD deficiency. Single-dose treatment is an important practical advantage compared to using PQ for the same purpose without an overall increase in adverse events in non-pregnant, non-G6PD-deficient adults.
Topics: Adult; Aminoquinolines; Antimalarials; Chloroquine; Drug Administration Schedule; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Vivax; Parasitemia; Placebos; Primaquine; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 32892362
DOI: 10.1002/14651858.CD010458.pub3 -
The Cochrane Database of Systematic... Jul 2020Within the context of heavy menstrual bleeding, pandemics impact upon women's assessment and treatment by healthcare providers.
BACKGROUND
Within the context of heavy menstrual bleeding, pandemics impact upon women's assessment and treatment by healthcare providers.
OBJECTIVES
To summarise the evidence from Cochrane Reviews evaluating interventions for heavy menstrual bleeding that are commonly available during pandemics.
METHODS
We sought published Cochrane Reviews, evaluating interventions that can continue during pandemics for women with heavy menstrual bleeding with no known underlying cause. We identified Cochrane Reviews by searching the Cochrane Database of Systematic Reviews in June 2020. The primary outcome was menstrual bleeding. Secondary outcomes included quality of life, patient satisfaction, side effects, and serious adverse events. We undertook the selection of systematic reviews, data extraction, and quality assessment in duplicate. We resolved any disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool, and the certainty of the evidence for each outcome using GRADE methods.
MAIN RESULTS
We included four Cochrane Reviews, with 11 comparisons, data from 44 randomised controlled trials (RCTs), and 3196 women. We assessed all the reviews to be high quality. Non-steroidal anti-inflammatory drugs (NSAIDs) NSAIDs may be more effective in reducing heavy menstrual bleeding than placebo (mean difference (MD) -124 mL per cycle, 95% confidence interval (CI) -186 to -62 mL per cycle; 1 RCT, 11 women; low-certainty evidence). Mefenamic acid may be similar to naproxen (MD 21 mL per cycle, 95% CI -6 to 48 mL per cycle; 2 RCTs, 61 women; low-certainty evidence), and NSAIDs may be similar to combined hormonal contraceptives for heavy menstrual bleeding (MD 25 mL per cycle, 95% CI -22 to 73 mL per cycle; 1 RCT, 26 women; low-certainty evidence). NSAIDs may be be less effective in reducing menstrual bleeding than antifibrinolytics (relative risk (RR) 0.70, 95% CI 0.58 to 0.85; 2 RCTs, 161 women; low-certainty evidence). We are uncertain whether NSAIDs reduce menstrual blood loss more than short-cycle progestogens (RR 0.80, 95% CI 0.49 to 1.32; 1 RCT 32 women; very low-certainty evidence). Antifibrinolytics Antifibrinolytics appear to be more effective in reducing heavy menstrual bleeding than placebo (MD -53 mL per cycle, 95% CI -63 to -44 mL per cycle; 4 RCTs, 565 women; moderate-certainty evidence). Antifibrinolytics may be similar to placebo on the incidence of side effects (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, 297 women; low-certainty evidence), and they are probably similar on the incidence of serious adverse events (thrombotic events; RR 0.10, 95% CI 0.00 to 2.46; 2 RCT, 468 women; moderate-certainty evidence). Antifibrinolytics may be more effective in reducing heavy menstrual bleeding than short-cycle progestogen (MD -111 mL per cycle, 95% CI -178 mL to -44 mL per cycle; 1 RCT, 46 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to short-cycle progestogens on quality of life (RR 1.67, 95% CI 0.76 to 3.64; 1 RCT, 44 women; very low-certainty evidence), patient satisfaction (RR 0.91, 95% CI 0.59 to 1.39; 1 RCT, 42 women; very low-certainty evidence), or side effects (RR 0.85, 95% CI 0.65 to 1.12; 3 RCTs, 211 women; very low-certainty evidence). We are uncertain whether antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with long-cycle progestogen (MD -9 points per cycle, 95% CI -30 to 12 points per cycle; 2 RCTs, 184 women; low-certainty evidence). Antifibrinolytics may increase self-reported improvement in menstrual bleeding when compared with long-cycle medroxyprogesterone acetate (RR 1.32, 95% CI 1.08 to 1.61; 1 RCT, 94 women; low-certainty evidence). Antifibrinolytics may be similar to long-cycle progestogens on quality of life (MD 5, 95% CI -2.49 to 12.49; 1 RCT, 90 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to long-cycle progestogens on side effects (RR 0.58, 95% CI 0.33 to 1.00; 2 RCTs, 184 women; very low-certainty evidence). There were no trials comparing antifibrinolytics to combined hormonal contraceptives. Combined hormonal contraceptives Combined hormonal contraceptives appear to be more effective for heavy menstrual bleeding than placebo or no treatment (RR 13.25, 95% CI 2.94 to 59.64; 2 RCTs, 363 women; moderate-certainty evidence). Combined hormonal contraceptives are probably similar to placebo on the incidence of side effects (RR 1.53, 95% CI 0.90 to 2.60; 2 RCTs, 411 women; moderate-certainty evidence). Progestogens There were no trials comparing progestogens to placebo. Limitations in the evidence included risk of bias in the primary RCTs, inconsistency between the primary RCTs, and imprecision in effect estimates.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that antifibrinolytics and combined hormonal contraceptives reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that NSAIDs reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with NSAIDs and short-cycle progestogens, but we are unable to draw conclusions about the effects of antifibrinolytics compared to long-cycle progestogens, on low-certainty evidence.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antifibrinolytic Agents; Contraceptives, Oral, Hormonal; Female; Humans; Mefenamic Acid; Menorrhagia; Pandemics; Placebos; Progestins; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 32700364
DOI: 10.1002/14651858.CD013651.pub2 -
The Cochrane Database of Systematic... Jun 2020Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other factors, the severity of the symptoms, a woman's age, her wish to get pregnant, and the presence of other pathologies. Heavy menstrual bleeding was classically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. Currently the definition is based on the woman's perception of excessive bleeding which is affecting her quality of life. The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss: users of the levonorgestrel-releasing intrauterine system (LNG-IUS) reported reductions of up to 90%. Insertion may, however, be regarded as invasive by some women, which affects its acceptability.
OBJECTIVES
To determine the effectiveness, acceptability and safety of progestogen-releasing intrauterine devices in reducing heavy menstrual bleeding.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL (from inception to June 2019); and we searched grey literature and for unpublished trials in trial registers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in women of reproductive age treated with LNG-IUS devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the certainty of evidence.
MAIN RESULTS
We included 25 RCTs (2511 women). Limitations in the evidence included risk of attrition bias and low numbers of participants. The studies compared the following interventions. LNG-IUS versus other medical therapy The other medical therapies were norethisterone acetate, medroxyprogesterone acetate, oral contraceptive pill, mefenamic acid, tranexamic acid or usual medical treatment (where participants could choose the oral treatment that was most suitable). The LNG-IUS may improve HMB, lowering menstrual blood loss according to the alkaline haematin method (mean difference (MD) 66.91 mL, 95% confidence interval (CI) 42.61 to 91.20; 2 studies, 170 women; low-certainty evidence); and the Pictorial Bleeding Assessment Chart (MD 55.05, 95% CI 27.83 to 82.28; 3 studies, 335 women; low-certainty evidence). We are uncertain whether the LNG-IUS may have any effect on women's satisfaction up to one year (RR 1.28, 95% CI 1.01 to 1.63; 3 studies, 141 women; I² = 0%, very low-certainty evidence). The LNG-IUS probably leads to slightly higher quality of life measured with the SF-36 compared with other medical therapy if (MD 2.90, 95% CI 0.06 to 5.74; 1 study: 571 women; moderate-certainty evidence) or with the Menorrhagia Multi-Attribute Scale (MD 13.40, 95% CI 9.89 to 16.91; 1 trial, 571 women; moderate-certainty evidence). The LNG-IUS and other medical therapies probably give rise to similar numbers of women with serious adverse events (RR 0.91, 95% CI 0.63 to 1.30; 1 study, 571 women; moderate-certainty evidence). Women using other medical therapy are probably more likely to withdraw from treatment for any reason (RR 0.49, 95% CI 0.39 to 0.60; 1 study, 571 women, moderate-certainty evidence) and to experience treatment failure than women with LNG-IUS (RR 0.34, 95% CI 0.26 to 0.44; 6 studies, 535 women; moderate-certainty evidence). LNG-IUS versus endometrial resection or ablation (EA) Bleeding outcome results are inconsistent. We are uncertain of the effect of the LNG-IUS compared to EA on rates of amenorrhoea (RR 1.21, 95% CI 0.85 to 1.72; 8 studies, 431 women; I² = 21%; low-certainty evidence) and hypomenorrhoea (RR 0.98, 95% CI 0.73 to 1.33; 4 studies, 200 women; low-certainty evidence) and eumenorrhoea (RR 0.55, 95% CI 0.30 to 1.00; 3 studies, 160 women; very low-certainty evidence). We are uncertain whether both treatments may have similar rates of satisfaction with treatment at 12 months (RR 0.95, 95% CI 0.85 to 1.07; 5 studies, 317 women; low-certainty evidence). We are uncertain if the LNG-IUS compared to EA has any effect on quality of life, measured with SF-36 (MD -14.40, 95% CI -22.63 to -6.17; 1 study, 33 women; very low-certainty evidence). Women with the LNG-IUS compared with EA are probably more likely to have any adverse event (RR 2.06, 95% CI 1.44 to 2.94; 3 studies, 201 women; moderate-certainty evidence). Women with the LNG-IUS may experience more treatment failure compared to EA at one year follow up (persistent HMB or requirement of additional treatment) (RR 1.78, 95% CI 1.09 to 2.90; 5 studies, 320 women; low-certainty evidence); or requirement of hysterectomy may be higher at one year follow up (RR 2.56, 95% CI 1.48 to 4.42; 3 studies, 400 women; low-certainty evidence). LNG-IUS versus hysterectomy We are uncertain whether the LNG-IUS has any effect on HMB compared with hysterectomy (RR for amenorrhoea 0.52, 95% CI 0.39 to 0.70; 1 study, 75 women; very low-certainty evidence). We are uncertain whether there is difference between LNG-IUS and hysterectomy in satisfaction at five years (RR 1.01, 95% CI 0.94 to 1.08; 1 study, 232 women; low-certainty evidence) and quality of life (SF-36 MD 2.20, 95% CI -2.93 to 7.33; 1 study, 221 women; low-certainty evidence). Women in the LNG-IUS group may be more likely to have treatment failure requiring hysterectomy for HMB at 1-year follow-up compared to the hysterectomy group (RR 48.18, 95% CI 2.96 to 783.22; 1 study, 236 women; low-certainty evidence). None of the studies reported cost data suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The LNG-IUS may improve HMB and quality of life compared to other medical therapy; the LNG-IUS is probably similar for HMB compared to endometrial destruction techniques; and we are uncertain if it is better or worse than hysterectomy. The LNG-IUS probably has similar serious adverse events to other medical therapy and it is more likely to have any adverse events than EA.
Topics: Antifibrinolytic Agents; Contraceptives, Oral; Endometrium; Female; Humans; Hysterectomy; Intrauterine Devices, Medicated; Levonorgestrel; Mefenamic Acid; Menorrhagia; Norethindrone; Progesterone; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid; Treatment Outcome
PubMed: 32529637
DOI: 10.1002/14651858.CD002126.pub4 -
BMC Women's Health Feb 2020Pictorial blood loss assessment charts (PBACs) represent the most widely used method to assess menstrual blood loss (MBL) in clinical trials. The aims of this review...
BACKGROUND
Pictorial blood loss assessment charts (PBACs) represent the most widely used method to assess menstrual blood loss (MBL) in clinical trials. The aims of this review were to: (1) determine the diagnostic accuracy of PBACs that have been validated against the reference alkaline hematin technique; (2) categorize the pitfalls of using obsolete and nonvalidated charts; (3) provide guidelines for development of a new PBAC or use of an existing chart to measure MBL in clinical trials; and (4) consider the feasibility of using pictorial charts in primary care.
METHODS
A literature review was conducted using Embase and MEDLINE databases. The review identified reports of women with self-perceived or actual heavy menstrual bleeding (HMB), bleeding disorders, abnormal uterine bleeding, leiomyomata (uterine fibroids) or endometriosis, and women undergoing treatment for HMB, as well as those with normal menstrual periods. Data were reviewed from studies that focused on the development and validation of PBACs and from those that used derivative noncertified charts to assess HMB.
RESULTS
Nine studies reported validation of PBAC scoring systems against the alkaline hematin technique. Across these studies, the sensitivity was 58-97%, the specificity was 7.5-95.5%, the positive and negative likelihood ratios were 1.1-13.8 and 0.14-0.56, respectively, and the diagnostic odds ratio was 2.6-52.4. The cut-off score above which the diagnosis of HMB was made ranged from 50 to 185. Several modifications of these PBACs were used in other studies; however, objective confirmation of their validity was not reported. Overall, there was widespread inconsistency of chart design, scoring systems, diagnostic cut-off limits and post-treatment outcome measures.
CONCLUSIONS
PBACs are best suited to the controlled and specific environment of clinical studies, where clinical outcome parameters are defined. The current lack of standardization precludes widespread use of the PBAC in primary care.
REVIEW REGISTRATION NUMBER
PROSPERO international prospective register of systematic reviews: CRD42016030083.
Topics: Adult; Clinical Trials as Topic; Diagnostic Techniques, Obstetrical and Gynecological; Female; Humans; Menorrhagia; Menstruation; Odds Ratio; Sensitivity and Specificity; Visual Analog Scale
PubMed: 32041594
DOI: 10.1186/s12905-020-0887-y -
Haemophilia : the Official Journal of... Mar 2020Women with inherited platelet receptor defects (IPRD) may have an increased risk of heavy menstrual bleeding (HMB) and postpartum haemorrhage (PPH).
INTRODUCTION
Women with inherited platelet receptor defects (IPRD) may have an increased risk of heavy menstrual bleeding (HMB) and postpartum haemorrhage (PPH).
AIM
To present a systematic overview of the literature on the prevalence and management of menstrual and obstetrical bleeding in women with IPRD.
METHODS
Electronic databases were searched for original patient data on the prevalence and management of HMB and PPH in women with known IPRD or who were being investigated for IPRD.
RESULTS
Sixty-nine papers (61 case reports/series and 8 cohort studies) were included. Overall, studies were rated as 'poor quality'. The included cohort studies reported HMB in 25% (13/52) of women with Bernard-Soulier syndrome and in 22.1% (34/154) of women with Glanzmann thrombasthenia. In total, 164 deliveries in women with IPRD were described. Excessive bleeding occurred in 16.9% (11/65) of deliveries described in the largest cohort. PPH occurred in 63.2% (55/87) of deliveries described in case reports/series. PPH occurred in 73.7% (14/19) of deliveries that were not covered by prophylaxis compared with 54.2% (32/59) of deliveries that were (OR = 2.36, 95% CI 0.75-7.40). Neonatal bleeding complications were reported in 10.0% (8/80) of deliveries. In all (6/6) deliveries with neonatal bleeding complications wherein the presence of alloantibodies was investigated, either antiplatelet or anti-HLA antibodies were detected.
DISCUSSION/CONCLUSION
Menstrual and particularly obstetrical bleeding problems frequently occur in women with IPRD, based on small case reports and series of poor quality. International collaboration, preferably on prospective studies, is needed to improve clinical management of women-specific bleeding in IPRD.
Topics: Blood Platelets; Female; Humans; Menorrhagia; Postpartum Hemorrhage
PubMed: 32004416
DOI: 10.1111/hae.13927 -
The Cochrane Database of Systematic... Sep 2019Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies...
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
To determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB.
SEARCH METHODS
We searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB.
DATA COLLECTION AND ANALYSIS
We identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision.
AUTHORS' CONCLUSIONS
NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Contraceptives, Oral, Combined; Dysmenorrhea; Female; Humans; Menorrhagia; Naproxen; Progesterone; Randomized Controlled Trials as Topic
PubMed: 31535715
DOI: 10.1002/14651858.CD000400.pub4 -
The Cochrane Database of Systematic... Aug 2019Heavy menstrual bleeding (HMB) is an important cause of ill health in women of reproductive age, causing them physical problems, social disruption and reducing their...
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in women of reproductive age, causing them physical problems, social disruption and reducing their quality of life. Medical therapy has traditionally been first-line therapy. Surgical treatment of HMB often follows failed or ineffective medical therapy. The definitive treatment is hysterectomy, but this is a major surgical procedure with significant physical and emotional complications, as well as social and economic costs. Less invasive surgical techniques, such as endometrial resection and ablation, have been developed with the purpose of improving menstrual symptoms by removing or ablating the entire thickness of the endometrium.
OBJECTIVES
To compare the effectiveness, acceptability and safety of techniques of endometrial destruction by any means versus hysterectomy by any means for the treatment of heavy menstrual bleeding.
SEARCH METHODS
Electronic searches for relevant randomised controlled trials (RCTs) targeted-but were not limited to-the following: the Cochrane Gynaecology and Fertility Group's specialised register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, and the ongoing trial registries. We made attempts to identify trials by examining citation lists of review articles and guidelines and by performing handsearching. Searches were performed in 1999, 2007, 2008, 2013 and on 10 December 2018.
SELECTION CRITERIA
Any RCTs that compared techniques of endometrial resection or ablation (by any means) with hysterectomy (by any technique) for the treatment of heavy menstrual bleeding in premenopausal women.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, extracted data and assessed trials for risk of bias.
MAIN RESULTS
We identified nine RCTs that fulfilled our inclusion criteria for this review. For two trials, the review authors identified multiple publications that assessed different outcomes at different postoperative time points for the same women. No included trials used third generation techniques.Clinical measures of improved bleeding symptoms and satisfaction rates were observed in women who had undergone hysterectomy compared to endometrial ablation. A slightly lower proportion of women who underwent endometrial ablation perceived improvement in bleeding symptoms at one year (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.85 to 0.93; 4 studies, 650 women, I² = 31%; low-quality evidence), at two years (RR 0.92, 95% CI 0.86 to 0.99; 2 studies, 292 women, I² = 53%) and at four years (RR 0.93, 95% CI 0.88 to 0.99; 2 studies, 237 women, I² = 79%). Women in the endometrial ablation group also showed improvement in pictorial blood loss assessment chart compared to their baseline (PBAC) score at one year (MD 24.40, 95% CI 16.01 to 32.79; 1 study, 68 women; moderate-quality evidence) and at two years (MD 44.00, 95% CI 36.09 to 51.91; 1 study, 68 women). Repeat surgery resulting from failure of the initial treatment was more likely to be needed after endometrial ablation than after hysterectomy at one year (RR 16.17, 95% CI 5.53 to 47.24; 927 women; 7 studies; I = 0%), at two years (RR 34.06, 95% CI 9.86 to 117.65; 930 women; 6 studies; I = 0%), at three years (RR 22.90, 95% CI 1.42 to 370.26; 172 women; 1 study) and at four years (RR 36.32, 95% CI 5.09 to 259.21;197 women; 1 study). The satisfaction rate was lower amongst those who had endometrial ablation at two years after surgery (RR 0.87, 95% CI 0.80 to 0.95; 4 studies, 567 women, I² = 0%; moderate-quality evidence), and no evidence of clear difference was reported between post-treatment satisfaction rates in groups at other follow-up times (1 and 4 years).Most adverse events, both major and minor, were more likely after hysterectomy during hospital stay. Women who had an endometrial ablation were less likely to experience sepsis (RR 0.19, 95% CI 0.12 to 0.31; participants = 621; studies = 4; I = 62%), blood transfusion (RR 0.20, 95% CI 0.07 to 0.59; 791 women; 5 studies; I = 0%), pyrexia (RR 0.17, 95% CI 0.09 to 0.35; 605 women; 3 studies; I = 66%), vault haematoma (RR 0.11, 95% CI 0.04 to 0.34; 858 women; 5 studies; I = 0%) and wound haematoma (RR 0.03, 95% CI 0.00 to 0.53; 202 women; 1 study) before hospital discharge. After discharge from hospital, the only difference that was reported for this group was a higher rate of infection (RR 0.27, 95% CI 0.13 to 0.58; 172 women; 1 study).Recovery time was shorter in the endometrial ablation group, considering hospital stay, time to return to normal activities and time to return to work; we did not, however, pool these data owing to high heterogeneity. Some outcomes (such as a woman's perception of bleeding and proportion of women requiring further surgery for HMB), generated a low GRADE score, suggesting that further research in these areas is likely to change the estimates.
AUTHORS' CONCLUSIONS
Endometrial resection and ablation offers an alternative to hysterectomy as a surgical treatment for heavy menstrual bleeding. Both procedures are effective, and satisfaction rates are high. Although hysterectomy offers permanent and immediate relief from heavy menstrual bleeding, it is associated with a longer operating time and recovery period. Hysterectomy also has higher rates of postoperative complications such as sepsis, blood transfusion and haematoma (vault and wound). The initial cost of endometrial destruction is lower than that of hysterectomy but, because retreatment is often necessary, the cost difference narrows over time.
Topics: Endometrial Ablation Techniques; Endometrium; Female; Humans; Hysterectomy; Hysteroscopy; Menorrhagia; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31463964
DOI: 10.1002/14651858.CD000329.pub3 -
The Cochrane Database of Systematic... Aug 2019Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their...
BACKGROUND
Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their physical, emotional, social and material quality of life. Whilst abnormal menstrual bleeding may be associated with underlying pathology, in the present context, HMB is defined as excessive menstrual bleeding in the absence of other systemic or gynaecological disease. The first-line therapy is usually medical, avoiding possibly unnecessary surgery. Of the wide variety of medications used to reduce HMB, oral progestogens were originally the most commonly prescribed agents. This review assesses the effectiveness of two different types and regimens of oral progestogens in reducing ovulatory HMB.This is the update of a Cochrane review last updated in 2007, and originally named "Effectiveness of cyclical progestagen therapy in reducing heavy menstrual bleeding" (1998).
OBJECTIVES
To determine the effectiveness, safety and tolerability of oral progestogen therapy taken either during the luteal phase (short cycle) or for a longer course of 21 days per cycle (long cycle), in achieving a reduction in menstrual blood loss in women of reproductive age with HMB.
SEARCH METHODS
In January 2019 we searched Cochrane Gynaecology and Fertility's specialized register, CENTRAL, MEDLINE, Embase, CINAHL and PsycInfo. We also searched trials registers, other sources of unpublished or grey literature and reference lists of retrieved trials. We also checked citation lists of review articles to identify trials.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing different treatments for HMB that included cyclical oral progestogens were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trials for risk of bias and extracted data. We contacted trial authors for clarification of methods or additional data when necessary. We only assessed adverse events if they were separately measured in the included trials. We compared cyclical oral progestogen in different regimens and placebo or other treatments. Our primary outcomes were menstrual blood loss and satisfaction with treatment; the secondary outcomes were number of days of bleeding, quality of life, compliance and acceptability of treatment, adverse events and costs.
MAIN RESULTS
This review identified 15 randomized controlled trials (RCTs) with 1071 women in total. Most of the women knew which treatment they were receiving, which may have influenced their judgements about menstrual blood loss and satisfaction. Other aspects of trial quality varied among trials.We did not identify any RCTs comparing progestogen treatment with placebo. We assessed comparisons between oral progestogens and other medical therapies separately according to different regimens.Short-cycle progestogen therapy during the luteal phase (medroxyprogesterone acetate or norethisterone for 7 to 10 days, from day 15 to 19) was inferior to other medical therapy, including tranexamic acid, danazol and the progestogen-releasing intrauterine system (Pg-IUS (off of the market since 2001)), releasing 60 mcg of progesterone daily, with respect to reduction of menstrual blood loss (mean difference (MD) 37.29, 95% confidence interval (CI) 17.67 to 56.91; I = 50%; 6 trials, 145 women). The rate of satisfaction and the quality of life with treatment was similar in both groups. The number of bleeding days was greater on the short cycle progestogen group compared to other medical treatments. Adverse events (such as gastrointestinal symptoms and weight gain) were more likely with danazol when compared with progestogen treatment. We note that danazol is no longer in general use for treating HMB.Long-cycle progestogen therapy (medroxyprogesterone acetate or norethisterone), from day 5 to day 26 of the menstrual cycle, is also inferior to the levonorgestrel-releasing intrauterine system (LNG-IUS), releasing tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss (MD 16.88, 95% CI 10.93 to 22.84; I = 87%; 4 trials, 355 women). A higher proportion of women taking norethisterone found their treatment unacceptable compared to women having Pg-IUS (Peto odds ratio (OR) 0.12, 95% CI 0.03 to 0.40; 1 trial, 40 women). However, the adverse effects of breast tenderness and intermenstrual bleeding were more likely in women with the LNG-IUS. No trials reported on days of bleeding or quality of life for this comparison.The evidence supporting these findings was limited by low or very low gradings of quality; thus, we are uncertain about the findings and there is a potential that they may change if we identify other trials.
AUTHORS' CONCLUSIONS
Low- or very low-quality evidence suggests that short-course progestogen was inferior to other medical therapy, including tranexamic acid, danazol and the Pg-IUS with respect to reduction of menstrual blood loss. Long cycle progestogen therapy (medroxyprogesterone acetate or norethisterone) was also inferior to the LNG-IUS, tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss.
Topics: Danazol; Female; Humans; Intrauterine Devices, Medicated; Medroxyprogesterone Acetate; Menorrhagia; Progesterone; Progestins; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 31425626
DOI: 10.1002/14651858.CD001016.pub3