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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CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL (from inception to June 2019); and we searched grey literature and for unpublished trials in trial registers.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 -
The Cochrane Database of Systematic... Feb 2019Menorrhagia or heavy menstrual bleeding (HMB) is an excessive blood loss that impairs a woman's quality of life, either physical, emotional, social or material. It is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Menorrhagia or heavy menstrual bleeding (HMB) is an excessive blood loss that impairs a woman's quality of life, either physical, emotional, social or material. It is benign and not associated with pregnancy or any other gynaecological or systemic disease. Medical treatments used to reduce excessive menstrual blood loss (MBL) include prostaglandin synthetase inhibitors, antifibrinolytics, oral contraceptive pills, and other hormones. The combined oral contraceptive pill (COCP) is claimed to have a variety of beneficial effects, inducing a regular shedding of a thinner endometrium and inhibiting ovulation, thus having the effect of both treating HMB and providing contraception. More recently, a contraceptive vaginal ring (CVR) has been trialled to investigate whether this treatment can provide similar benefits to COCP while lessening hormonal systemic exposure. This review is an update of a review which originally focused on COCP alone. The scope of the review has been widened to consider other types of delivery of combined hormonal contraceptives for reduction of MBL.
OBJECTIVES
To determine the efficacy of combined hormonal contraceptives (pills, vaginal ring or patch) compared with other medical therapies, placebo, or no therapy in the treatment of HMB. A secondary objective was to compare the COCP with the CVR.
SEARCH METHODS
We searched the Gynecology and Fertility Group trials register, MEDLINE, Embase, CENTRAL, CINAHL and PsycINFO (search dates: Oct 1996, May 2002, June 2004, April 2006, June 2009, July 2017 and September 2018) for all randomised controlled trials (RCTs) of COCP and CVR for the treatment of HMB. We also searched trial registers and the reference lists of retrieved studies for additional trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of the use of COCP or CVR compared with no treatment, placebo, or other medical therapies for women with HMB and regular menstrual cycles.
DATA COLLECTION AND ANALYSIS
All assessments of trial quality and data extraction were performed unblinded by at least two review authors. Our primary review outcomes were treatment success, menstrual bleeding (assessed objectively, semi-objectively or subjectively), and participant satisfaction with treatment. Secondary outcomes were adverse events, quality of life, and haemoglobin level.
MAIN RESULTS
We identified eight RCTs involving 805 participants. Two trials comparing COCP with placebo were considered to be moderate quality and the remaining studies were low to very low quality, mainly because of serious risk of bias from lack of blinding and concerns over precision.COCP versus placeboCOCP, with a step-down oestrogen and step-up progestogen regimen, improved response to treatment (return to menstrual 'normality') (OR 22.12, 95% CI 4.40 to 111.12; 2 trials; 363 participants; I = 50%; moderate-quality evidence), and lowered MBL (OR 5.15, 95% CI 3.16 to 8.40; 2 trials; 339 participants; I = 0%; moderate-quality evidence) when compared to placebo. The results suggested that, if the chance of 'successful' treatment was 3% in women taking placebo, then COCP increased this chance from 12% to 77% in women with unacceptable HMB. Minor adverse events, in particular breast pain, were more common with COCP. No study in this comparison reported semi-objectively assessed MBL or participant satisfaction with treatment.COCP versus other medical treatmentsNon-steroidal anti-inflammatory drugs (NSAIDs)There was insufficient evidence to determine whether the COCP reduced MBL when compared to NSAIDs (mefenamic acid and naproxen). No study in this comparison reported semi-objectively assessed MBL, subjectively assessed MBL, participant satisfaction with treatment or adverse events.Levonorgestrel-releasing intrauterine system (LNG IUS)The LNG IUS was more effective than COCP in reducing MBL (OR 0.21, 95% CI 0.09 to 0.48; 2 trials; 151 participants; I = 0%; low-quality evidence) but it was not clear whether satisfaction with treatment or adverse effects varied according to which treatment was used. No study in this comparison reported semi-objectively assessed MBL or subjectively assessed MBL.Contraceptive vaginal ring (CVR) versus other medical treatmentsCOCP COCP was compared with CVR in two trials. There were discrepancies between some of the findings and there was no evidence of a benefit for one treatment compared to the other for response to treatment, MBL or participant satisfaction with treatment. There was a greater likelihood of nausea with COCP. No study in this comparison reported objectively assessed MBL or subjectively assessed MBL.ProgestogensCVR was compared to long course progestogens in one trial. It is possible that CVR increased the odds of satisfaction; but we are uncertain whether CVR improved MBL. The evidence was based on small numbers of participants and was very low quality, so definitive conclusions could not be reached. No study in this comparison reported objectively assessed MBL, subjectively assessed MBL, or adverse events.
AUTHORS' CONCLUSIONS
Moderate-quality evidence suggests that the combined oral contraceptive pill over six months reduces HMB in women with unacceptable HMB from 12% to 77% (compared to 3% in women taking placebo). When compared with other medical options for HMB, COCP was less effective than the LNG IUS. Limited evidence suggested that COCP and CVR had similar effects. There was insufficient evidence to determine comparative efficacy of combined hormonal contraceptives with NSAIDs, or long course progestogens.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Danazol; Drug Therapy, Combination; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Mefenamic Acid; Menorrhagia; Naproxen; Nausea; Placebos; Progestins; Randomized Controlled Trials as Topic
PubMed: 30742315
DOI: 10.1002/14651858.CD000154.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