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 We also searched trials registers, other sources of unpublished or grey literature and reference lists of retrieved trials.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.
OBIETTIVO: Per confrontare l'efficacia di trattamenti non chirurgici abnormal sanguinamento uterino per sanguinamento controllo, la qualità della vita (QOL), il dolore, la salute sessuale, la soddisfazione del paziente, i trattamenti aggiuntivi necessari, e gli eventi avversi.
FONTI DI DATI: MEDLINE, database Cochrane, e Clinicaltrials.gov state perquisite da inizio a maggio 2012. Sono stati inclusi studi randomizzati controllati di trattamenti non chirurgici per sanguinamento uterino anomalo presunti secondaria a disfunzione endometriale e sanguinamento uterino anomalo presume secondaria a disfunzione ovulatoria. Gli interventi inclusi il sistema intrauterino di levonorgestrel, contraccettivi orali combinati (OCP), progestinici, farmaci anti-infiammatori non steroidei (FANS), e antifibrinolitici. Gonadotropina-agonisti dell'ormone rilasciante, danazolo, e placebo sono stati autorizzati come comparatori.
MODALITA 'DI SELEZIONE DEGLI STUDI: Due revisori proiettati independently 5848 citazioni ed estratti prove ammissibili. Gli studi sono stati valutati per la qualità e la forza delle prove.
Tabulazione, INTEGRAZIONE, E RISULTATI: Ventisei articoli incontrato i criteri di inclusione. Per la riduzione del sanguinamento mestruale nelle donne con sanguinamento uterino anomalo presume secondaria a disfunzione endometriale, il sistema intrauterino di levonorgestrel (71-95% di riduzione), OCP combinati (35-69% di riduzione), estesa progestinici orali ciclabili (87% di riduzione), tranexamico acido (26-54% di riduzione), e FANS (10-52% di riduzione) sono stati tutti i trattamenti efficaci. Il sistema intrauterino di levonorgestrel, OCP combinati, e antifibrinolitici erano tutti superiori ai progestinici luteale-fase (20% di aumento di sanguinamento riduzione del 67%). Il sistema intrauterino di levonorgestrel è stata superiore a OCP combinati e FANS. Antifibrinolytics erano superiori ai FANS per la riduzione del sanguinamento mestruale. I dati sono stati limitati su altri risultati importanti come la qualità di vita per le donne con sanguinamento uterino anomalo presume secondaria a disfunzione endometriale e per tutti gli esiti per le donne con sanguinamento uterino anomalo presume secondaria a disfunzione ovulatoria.
CONCLUSIONE: Per la riduzione della perdita ematica media nelle donne con sanguinamento mestruale pesante presume secondario al sanguinamento uterino anomalo presume secondaria a disfunzione endometriale, si consiglia l'utilizzo del sistema intrauterino di levonorgestrel oltre OCP, progestinici fase luteale, e FANS. Per gli altri risultati (QOL, il dolore, la salute sessuale, la soddisfazione del paziente, i trattamenti aggiuntivi necessari, e gli eventi avversi) e per il trattamento di sanguinamento uterino anomalo presume secondaria a disfunzione ovulatoria, siamo stati in grado di formulare raccomandazioni sulla base dei limitati dati disponibili.
BACKGROUND: Una varietà di trattamenti farmacologici e chirurgici sono stati sviluppati per sanguinamento mestruale pesante (HMB), che possono avere conseguenze negative fisiche, sociali, psicologici ed economici. Abbiamo condotto una revisione sistematica della letteratura e-trattamento-confronto misto (MTC) meta-analisi dei dati disponibili di studi clinici controllati randomizzati (RCT) di ricavare stime di efficacia per 8 classi di trattamenti per l'HMB, per informare l'analisi salute-economica e studi futuri .
METODI: Una revisione sistematica ha identificato studi randomizzati che hanno fornito dati sulla perdita di sangue mestruale (MBL) al basale e una o più volte di follow-up. Sono state considerate otto classi di trattamento: COC, danazolo, ablazione endometriale, LNG-IUS, placebo, progestinici dato per meno di 2 settimane di 4 durante il ciclo mestruale, progestinici dato per quasi tre settimane di 4, e TXA. La misura primaria di efficacia era la percentuale di donne che hanno raggiunto MBL <80 ml per ciclo (al mese), misurata con il metodo ematina alcalino. Un punteggio inferiore a 100 su un grafico pittorico valutazione di sangue perdita consolidata (PBAC) era considerato un sostituto accettabile per MBL <80 mL. Stime di efficacia per classe di trattamento e il tempo sono stati ottenuti da un modello bayesiano MTC. Il modello include anche gli effetti per classe di trattamento, lo studio, e la combinazione di classe di trattamento e di studio e di un adeguamento per valore basale medio di MBL. Diverse sfide metodologiche complicato l'analisi. Alcuni studi hanno riportato varie statistiche riassuntive per MBL o PBAC, che richiede la stima (con minore precisione) del% MBL <80 ml o% PBAC <100. Inoltre, ha riferito il follow-up volte variavano notevolmente.
RISULTATI: La rete prove coinvolti 34 studi randomizzati, con follow-up tempi di 1-36 mesi. Efficacia a 3 mesi di follow-up (stimato come la mediana posteriore) variava dal 87,5% per il sistema intrauterino a rilascio di levonorgestrel (LNG-IUS), al 14,2% per i progestinici somministrati per meno di 2 settimane su 4 a ciclo mestruale. Gli intervalli credibili al 95% per la maggior parte delle stime erano piuttosto ampia, soprattutto a causa della limitata evidenza per molte combinazioni di classe trattamento e follow-up tempo e l'incertezza di fare previsioni% MBL <80 ml o% PBAC <100 da statistiche riassuntive.
CONCLUSIONI: LNG-IUS e ablazione endometriale sono molto efficaci nel trattamento di HMB. Lo studio ha dato indicazioni utili sull'utilizzo di MTC in reti di prove sparse. La diversità delle misure di risultato e dei tempi di follow-up in letteratura HMB presentato notevoli sfide. Gli intervalli credibili bayesiani riflettono le varie fonti di incertezza.
OBIETTIVO: Per valutare l'efficacia di acido tranexamico nel trattamento della idiopatica e non funzionali sanguinamento mestruale pesante.
DESIGN: revisione sistematica.
POPOLAZIONE: Le donne con una diagnosi di idiopatica e non funzionali sanguinamento mestruale pesante trattata con acido tranexamico.
METODI: sono state condotte ricerche elettroniche nelle banche dati della letteratura fino al febbraio 2011 da due revisori indipendenti. Sono stati inclusi tutti gli studi riguardanti l'efficacia di acido tranexamico per il trattamento di pesante sanguinamento uterino. Pazienti in stato di gravidanza, post-menopausa e cancro sono stati esclusi.
MISURE PRINCIPALI DEL RISULTATO: Effetto del trattamento con acido tranexamico obiettivo sulla riduzione del sanguinamento mestruale e miglioramento della qualità della vita dei pazienti.
Risultati: un totale di 10 studi hanno soddisfatto i nostri criteri di inclusione. Prove disponibili indicano che la terapia con acido tranexamico in donne con menorragia idiopatica portato nel 34-54% di riduzione in perdita di sangue mestruale. Dopo il trattamento con acido tranexamico, paziente sua qualità della vita parameters migliorato 46-83%, rispetto al 15-45% per il trattamento noretisterone. Quando confrontato con placebo, l'uso di acido tranexamico significativamente ridotto la perdita di sangue del 70% nelle donne con menorragia secondaria ad un dispositivo intrauterino (p <0,001). Prove limitate indicano i benefici potenziali nei pazienti con fibroma menorragia. Nessun evento tromboembolico è stata riportata in tutti gli studi analizzati.
CONCLUSIONI: prove disponibili indicano che il trattamento con acido tranexamico è efficace e sicuro, e potrebbe potenzialmente migliorare la qualità della vita dei pazienti affetti da idiopatica e non funzionali sanguinamento mestruale pesante. I dati sulla efficacia terapeutica di acido tranexamico nei pazienti con fibromi sintomatici sono limitate e ulteriori studi sono dunque necessari.
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.
