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CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL (from inception to June 2019); and we searched grey literature and for unpublished trials in trial registers.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.
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.
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; I2 = 50%; moderate-quality evidence), and lowered MBL (OR 5.15, 95% CI 3.16 to 8.40; 2 trials; 339 participants; I2 = 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; I2 = 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.
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; I2 = 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; I2 = 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.
BACKGROUND: Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to reduce bleeding by inhibiting clot-dissolving enzymes in the endometrium.Historically, there has been some concern that using the antifibrinolytic tranexamic acid (TXA) for HMB may increase the risk of venous thromboembolic disease. This is an umbrella term for deep venous thrombosis (blood clots in the blood vessels in the legs) and pulmonary emboli (blood clots in the blood vessels in the lungs).
OBJECTIVES: To determine the effectiveness and safety of antifibrinolytic medications as a treatment for heavy menstrual bleeding.
SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials registers in November 2017, together with reference checking and contact with study authors and experts in the field.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing antifibrinolytic agents versus placebo, no treatment or other medical treatment in women of reproductive age with HMB. Twelve studies utilised TXA and one utilised a prodrug of TXA (Kabi).
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary review outcomes were menstrual blood loss (MBL), improvement in HMB, and thromboembolic events.
MAIN RESULTS: We included 13 RCTs (1312 participants analysed). The evidence was very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding, and poor reporting of study methods), imprecision and inconsistency.Antifibrinolytics (TXA or Kabi) versus no treatment or placeboWhen compared with a placebo, antifibrinolytics were associated with reduced mean blood loss (MD -53.20 mL per cycle, 95% CI -62.70 to -43.70; I² = 8%; 4 RCTs, participants = 565; moderate-quality evidence) and higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09; 3 RCTS, participants = 271; moderate-quality evidence). This suggests that if 11% of women improve without treatment, 43% to 63% of women taking antifibrinolytics will do so. There was no clear evidence of a difference between the groups in adverse events (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, participants = 297; low-quality evidence). Only one thromboembolic event occurred in the two studies that reported this outcome.TXA versus progestogensThere was no clear evidence of a difference between the groups in mean blood loss measured using the Pictorial Blood Assessment Chart (PBAC) (MD -12.22 points per cycle, 95% CI -30.8 to 6.36; I² = 0%; 3 RCTs, participants = 312; very low quality evidence), but TXA was associated with a higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80; I² = 32%; 5 RCTs, participants = 422; low-quality evidence). This suggests that if 46% of women improve with progestogens, 61% to 83% of women will do so with TXA.Adverse events were less common in the TXA group (RR 0.66, 95% CI 0.46 to 0.94; I² = 28%; 4 RCTs, participants = 349; low-quality evidence). No thromboembolic events were reported in any group.TXA versus non-steroidal anti-inflammatory drugs (NSAIDs)TXA was associated with reduced mean blood loss (MD -73.00 mL per cycle, 95% CI -123.35 to -22.65; 1 RCT, participants = 49; low-quality evidence) and higher likelihood of improvement (RR 1.43, 95% CI 1.18 to 1.74; 1
AUTHORS' CONCLUSIONS: Antifibrinolytic treatment (such as TXA) appears effective for treating HMB compared to placebo, NSAIDs, oral luteal progestogens, ethamsylate, or herbal remedies, but may be less effective than LIUS. There were too few data for most comparisons to determine whether antifibrinolytics were associated with increased risk of adverse events, and most studies did not specifically include thromboembolism as an outcome.
Antecedentes: El sangrado menstrual intenso perjudica significativamente la calidad de vida de muchas mujeres sanas. La percepción de sangrado menstrual abundante es subjetiva y la administración generalmente depende de qué síntomas son aceptables para el individuo. Las opciones quirúrgicas incluyen cirugía conservadora (resección u ablación uterina) e histerectomía. Las opciones de tratamiento médico incluyen medicamentos orales y un dispositivo intrauterino que libera hormonas (LNG-IUS). OBJETIVOS: Comparar la efectividad, la seguridad y la aceptabilidad de la cirugía versus la terapia médica para el sangrado menstrual abundante. Métodos de búsqueda: Se realizaron búsquedas en las siguientes bases de datos desde el inicio hasta enero de 2016: Registro de ensayos del Grupo Cochrane de Ginecología y Fertilidad, Registro Central Cochrane de Ensayos Controlados (CENTRAL), MEDLINE, EMBASE, PsycINFO y ensayos clínicos (clinical trials.gov e ICTRP) . También se realizaron búsquedas en las listas de referencias de artículos recuperados. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorios (ECA) que comparan cirugía conservadora o histerectomía versus terapia médica (oral o intrauterina) para el sangrado menstrual abundante. Dos revisores seleccionaron de forma independiente los estudios, evaluaron su riesgo de sesgo y extrajeron los datos. Nuestros resultados primarios fueron sangrado menstrual, tasa de satisfacción y eventos adversos. Cuando procede, agrupamos los datos para calcular las razones de riesgo agrupadas (RR) o las diferencias de medias, con intervalos de confianza del 95% (IC), utilizando un modelo de efectos fijos. Se evaluó la heterogeneidad con la estadística I (2) y se evaluó la calidad de la evidencia utilizando los métodos GRADE. Se incluyeron 15 ECAs de grupos paralelos (1289 mujeres). Las intervenciones quirúrgicas incluyeron histerectomía y resección endometrial o ablación. Las intervenciones médicas incluyeron la medicación oral y el dispositivo intrauterino liberador de levonorgestrel (LNG-IUS). La calidad general de la evidencia para diferentes comparaciones varió de muy baja a moderada. Las principales limitaciones fueron la falta de cegamiento, desgaste e imprecisión. Por otra parte, fue difícil interpretar a largo plazo los resultados del estudio ya que muchas mujeres asignadas al azar a intervenciones médicas posteriormente se sometieron a cirugía. La cirugía (resección endometrial) fue más efectiva en el control de la hemorragia a los cuatro meses (RR 2,66, IC del 95%: 1,94 a 3,64, un ECA, 186 mujeres, evidencia de calidad moderada) y también a los dos años (RR 1,29, IC del 95% 1,06 a 1,57, un ECA, 173 mujeres, evidencia de baja calidad). No hubo evidencia de diferencias entre los grupos a los cinco años (RR 1,14, IC del 95%: 0,97 a 1,34, un ECA, 140 mujeres, evidencia de muy baja calidad). La satisfacción con el tratamiento fue mayor en el grupo quirúrgico a los dos años 1,40, IC del 95%: 1,13 a 1,74, un ECA, 173 mujeres, evidencia de calidad moderada), pero no hubo evidencia de diferencia entre los grupos a los cinco años (RR 1,13; IC del 95%: 0,94 a 1,37; , Evidencia de muy baja calidad). Hubo menos eventos adversos en el grupo quirúrgico a los cuatro meses (RR 0,26, IC 95 0,15 a 0,46, un ECA, 186 mujeres). Estos hallazgos requieren una interpretación cautelosa, ya que el 59% de las mujeres asignadas al azar al grupo de medicación oral habían tenido cirugía en dos años y el 77% en cinco años. Cirugía versus LNG-IUS Cuando se comparó la histerectomía con el IU-LNG, el grupo de histerectomía tenía más probabilidades de tener un control objetivo de la hemorragia al año (RR 1,11, IC del 95%: 1,05 a 1,19, un ECA, 223 mujeres). No hubo evidencia de una diferencia en la calidad de vida entre los grupos a los cinco o 10 años, pero en 10 años 46% de las mujeres originalmente asignadas a IU-LNG habían sido sometidas a histerectomía. Los efectos adversos asociados con la histerectomía incluyeron complicaciones quirúrgicas tales como perforación de la vejiga o del intestino y fístula vesicovaginal. Los efectos adversos asociados con LNG-IUS fueron sangrado continuo y síntomas hormonales. Cuando se comparó la cirugía conservadora con el LNG-IUS, en un año el grupo quirúrgico era más propenso a tener un control subjetivo de la hemorragia (RR 1,19; IC del 95%: 1,07 a 1,32; Cinco ECA, 281 mujeres, evidencia de baja calidad, I (2) = 15%). Los índices de satisfacción fueron mayores en el grupo quirúrgico al año (RR 1,16, IC del 95% 1,04, 1,28, seis ECA, 442 mujeres, I (2) = 27%), pero este hallazgo fue sensible a la elección del modelo estadístico y El uso de un modelo de efectos aleatorios no mostró evidencia concluyente de una diferencia entre los grupos. No hubo evidencia de una diferencia entre los grupos en los índices de satisfacción a los dos años (RR 0,93, IC del 95%: 0,81 a 1,08, dos ECA, 117 mujeres, I (2) = 1%). (Como sangrado y manchas) en el grupo quirúrgico (RR 0,36, IC del 95%: 0,15 a 0,82, tres ECA, evidencia de calidad moderada). No estaba claro qué proporción de mujeres asignadas a LNG-IUS se sometieron a cirugía a largo plazo de seguimiento, ya que había pocos datos más allá de un año. CONCLUSIONES DE LOS AUTORES: La cirugía, especialmente la histerectomía, reduce el sangrado menstrual más que el tratamiento médico al año. No hay evidencia concluyente de una diferencia en las tasas de satisfacción entre cirugía y LNG-IUS, aunque los efectos adversos como sangrado y manchas son más probables de ocurrir con LNG-IUS. La medicación oral se adapta a una minoría de mujeres a largo plazo, y el dispositivo LNG-IUS proporciona una mejor alternativa a la cirugía en la mayoría de los casos. Aunque la histerectomía es un tratamiento definitivo para el sangrado menstrual abundante, puede causar complicaciones serias para una minoría de mujeres. La mayoría de las mujeres pueden estar bien aconsejadas para intentar un tratamiento menos radical como tratamiento de primera línea. Tanto el LNG-IUS como la cirugía conservadora parecen ser seguros, aceptables y eficaces.
La histerectomía es uno de los procedimientos quirúrgicos más comunes en el mundo desarrollado, que ocurre principalmente en las mujeres premenopáusicas, con resultados contradictorios con respecto a bienestar psicológico post-operatorio. Esta revisión tiene como objetivo informar a la práctica mediante el examen de si la histerectomía predice resultados de la depresión o de ansiedad. Se realizaron búsquedas en PubMed, EMBASE, PsycINFO y bases de datos electrónicas para artículos publicados antes de noviembre de 2012. Las listas de referencias de los artículos pertinentes se realizaron búsquedas manuales, y las opiniones de expertos se buscaron. Estudios arbitrados que investigan una asociación entre la histerectomía para condiciones benignas (no cancerosas) y los síntomas postoperatorios de la depresión o la ansiedad se eligieron para esta revisión. Dos autores extrajeron de forma independiente los datos de los artículos originales. Se contactó con los autores de los estudios relevantes para los datos que no pudieron ser extraídos de los artículos publicados. Review Manager 5.1 se utiliza en todo el metanálisis para calcular los riesgos relativos (RR) y la diferencia ponderada de medias estandarizada (WstdMD), y sus correspondientes intervalos de confianza del 95% (IC). Un modelo de efectos aleatorios se utilizó en el análisis de datos y verificado mediante un modelo de efectos fijos. En general, la histerectomía se asoció con un menor riesgo de depresión clínicamente relevante (RR = 1,69, 95% CI 1,19-2,38). Además, la histerectomía se asoció con una disminución en resultados de la depresión estandarizadas (diferencia de medias estandarizada (DME) CI 0,38 (95% 0,27 a 0,49)). Por el contrario, no hubo asociación significativa entre la histerectomía y el riesgo de ansiedad clínicamente relevante (RR = 1,41, 95% CI 0,72-2,75). En conclusión, los datos de antes y después de los estudios sugieren que la histerectomía para las enfermedades ginecológicas benignas no se asocia negativamente con la ansiedad y puede ser positiva en lugar de asociado negativamente con la depresión.
ANTECEDENTES: El objetivo de este estudio fue comparar los efectos del sistema intrauterino liberador de levonorgestrel (LNG-IUS) con el tratamiento médico convencional para reducir el sangrado menstrual abundante.
MATERIAL Y MÉTODOS: Los estudios pertinentes se identificaron mediante una búsqueda en MEDLINE, EMBASE, el Registro Cochrane Central de Ensayos Controlados, y los registros clínicos aleatorios (desde su inicio hasta abril 2014). Se incluyeron ensayos controlados aleatorios que compararon el SIU-LNG con el tratamiento médico convencional (ácido mefenámico, ácido tranexámico, noretindrona, la inyección de acetato de medroxiprogesterona, o píldoras anticonceptivas orales combinadas) en pacientes con menorragia.
RESULTADOS: Ocho ensayos controlados aleatorios que incluyeron 1.170 mujeres (LNG-IUS, n = 562; tratamiento médico convencional, n = 608) cumplieron los criterios de inclusión. El LNG-IUS fue superior al tratamiento médico convencional para reducir la pérdida de sangre menstrual (medida por el método de hematina alcalina o estimado por las puntuaciones tabla de evaluación sangrado pictóricas). Más mujeres se mostraron satisfechos con el SIU-LNG que con el uso de un tratamiento médico convencional (odds ratio [OR] 5,19, 95% intervalo de confianza [IC] 2,73-9,86). En comparación con el tratamiento médico convencional, el LNG-IUS se asoció con una menor tasa de interrupción (14,6% vs. 28,9%; OR 0,39; IC del 95%: 0,20 a 0,74) y menos fracasos del tratamiento (9,2% frente a 31,0%; OR 0,18 , 95% CI 0,10-0,34). Por otra parte, la calidad de la evaluación de la vida favoreció LNG-IUS sobre el tratamiento médico convencional, aunque el uso de diversas mediciones limita nuestra capacidad para combinar los datos de pruebas más potente. Los acontecimientos adversos graves fueron estadísticamente comparable entre los tratamientos.
CONCLUSIONES: El LNG-IUS fue la primera opción más eficaz para la gestión de la menorragia en comparación con el tratamiento médico convencional. A largo plazo, se requieren ensayos aleatorios para investigar más a fondo los resultados basados en el paciente y evaluar la relación coste-eficacia del LNG-IUS y otros tratamientos médicos.
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.
