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Table 8.9Etamsylate for treatment of HMB – comparative studies

Bibliographic informationStudy type and evidence levelNo. of patientsPatient characteristicsIntervention and comparisonFollow-upOutcome measuresEffect sizeSource of funding and additional comments
Bonnar 1996305Randomised; intention to treat

EL = 1−
81 in total: 29 to etamsylate; 25 mefenamic acid; 27 tranexamic acid. 2 etamsylate, 2 mefenamic acid, 1 tranexamic acid excluded.Population characteristics: Complaint of HMB; organic causes of menorrhagia excluded; history of renal or hepatic impairment, previous thromoembolic disease, inflammatory bowel disease, ulcers, coagulation or fibrionolytic disorders were excluded.

A university O&G department

Country: Ireland
Etamsylate (500 mg × 4); mefenamic acid (500 mg × 3); tranexamic acid (1 g × 4); no treatment

treatments vs no treatment periods
6 consecutive menstrual cycles: 3 baseline; 3 treatmentMBL – alkaline haematin test; duration of bleeding; sanitary towel use; side effectsTranexamic acid: MBL reduced by 89 ml (24 to 214 ml; 54% reduction; P < 0.001). Mean MBL 164 (n = 78) in control and 75m (n = 72) (89 ml difference) in treatment. Tranexamic acid vs etamsylate: = −97 ml (95% CI 140 to 154; P < 0.001); vs mefenamic acid = – 56 ml ((95% CI 90 to 2 ml; P < 0.05)) (Perhaps misprint: may be 46 ml based on other figures in paper.) mefenamic acid: 20% reduction in MBL (P < 0.001).

Etamsylate – no effect on MBL.

77% of patient wanted to continue with tranexamic acid after trial.

11 etamsylate (40%), 3 mefenamic acid (13%), 4 tranexamic acid (15%) withdraw from study. Poor efficacy was main reason. Reported side effects were nausea, headache and dizziness – no statistical assessment provided.

Etamsylate – 8 ml increase with etamsylate, but no statistical difference Mean MBL in pre-treatment = 170 ml (n = 81) vs 175 ml (n = 63) (+3%) (figures do not match reported figures) during treatment. Difference between treatments: +97 ml (95% CI 140 to 154; P < 0.001) against tranexamic acid; +51 ml (95% CI −96 to −6; P < 0.05) against mefenamic acid.

33% of patients wanted to continue with etamsylate after trial.

11 etamsylate (40%), 3 mefenamic acid (13%), 4 tranexamic acid (15%) withdraw from study. Poor efficacy was main reason.

Mefenamic acid: a 43 ml (82 to 179) (20%) reduction in MBL (P < 0.001). Mean MBL in pre-treatment = 186 ml (n = 69) and 148 ml (n = 64) during treatment (difference of 38 ml). mefenamic acid reduce MBL by 56 ml (Perhaps misprint, should be 46 ml) less than tranexamic acid (95% CI 90 to 2 ml; P < 0.05)

and 51 ml (95% CI −96 to −6; P < 0.05) more than against etamsylate.

74% of women wanted to continue with mefenamic acid after the trial. 77% with tranexamic, and 33% with etamsylate.

11 etamsylate (40%), 3 mefenamic acid (13%), 4 tranexamic acid (15%) withdraw from study. Poor efficacy was main reason.

Side effects were nausea, dizziness and headaches.
Funding source: Commercial (Pharmacia) and state (Health Research Board of Ireland) funding

Study summary: Tranexamic acid given at start of menstrual cycle would reduce MBL by half.
kRandomised; placebo-controlled; crossover; double blind

EL = 1+
31 entered. Only 9 primary menorrhagia patients. 9 patients were excluded from analysis.Population characteristics: Inclusion/exclusion – complaint of HMB, a regular menstrual cycle, no organic disease. IUD HMB patients also included.

Women referred to O&G department for HMB

Country: UK
Etamsylate; placebo

treatment vs treatment
4 consecutive cyclesMenstrual blood loss – alkaline haematin test; tampon use; side effectsFor primary HMB menorrhagia only (n = 9): Difference between etamsylate and placebo = 59.4 ml (P = < 0.01); Mean MBL reduction with etamsylate = 49.7 ± 2.3 SE. 95% CI 44.2 to 55.2, −46% MBL.

Side effects: 34% (17 of 50) in placebo periods and 34% (18 of 53) in etamsylate. None reported as serious.
Funding source: Not reported

Study summary: ‘The results of the study suggest that etamsylate is a safe and effective agent in the treatment of primary menorrhagia…’
Lethaby 2004300Systematic review; meta-analysis

EL = 1++
MBLAntifibrinolytics vs etamsylate: 1 study – MBL = −97 ml (−134.36 to −59.64) in favour of TXA.

Side effects reported. Withdrawals due to adverse events: RR 0.78 [95% CI 0.19, 3.15].

Meta-analysis of 2 RCTs of tranexamic vs placebo (n = 48) −110.17 [95% CI −146.54, −73.81); z = 5.94 (P = 0.001). Antifibrinolytic vs NSAIDs: 1 study (n = 49) – MBL = −46 (−76.02 to −15.98). Antifibrinolytic vs etamsylate: 1 study (n = 50) – MBL = −97 ml (−134.36 to – 59.64).

Side effects: Withdrawals due to adverse events vs NSAIDs (1 study) RR = 2.65 [0.3, 23.77]. Vs Etamsylate (1 study) RR = 0.78 [0.19, 3.15].
Funding source: No funding
Lethaby 2004308Systematic review

EL = 1++
NSAID vs oral progestogens T (2 RCTs, n = 48) MBL −22.97 [46.57, 0.62] in favour of NSAIDs. NSAIDs vs progesterone IUS (1 RCT, n = 16) MBL −4 [−31.23, 23.23]. NSAID vs OCP (I trial, n = 26) MBL 25.25 [−22.34, 72.84].

NSAIDs vs etamsylate = −42.88 ml/cycle [95% CI −86.25 to 0.50
Chamberlain 1991310Minimisation; double-blind; double-dummy.

EL = 1+
44 in entered, 34 finished: 22 in each arm. 6 of 22 in etamsylate and 4 of 22 in mefenamic group did not complete study.Population characteristics: Inclusion: Women 18–55; menorrhagia 80 ml>.

Exclusion: malignant disease excluded; taking oral contraceptives excluded; hepatic impairment; want to become pregnant during study period; allergies to prostaglandins; anaemic; fitted with IUD; had fibroids.

Setting not specified, but study from district general hospital O&G department.

Country: UK
etamsylate 500 mg × 4; mefenamic 500 mg × 3

treatment vs treatment
4 consecutive cycles: 2 baseline; 2 treatmentMBL – alkaline haematin test; tampon use; side effects.Etamsylate reduced MBL by 20%. mefenamic acid reduced MBL by 24%. Reduction in MBL for etamsylate in 2 of 3 periods (P < 0.01) – 95% do not cross zero; significant for mefenamic acid on all three periods (P < 0.01, < 0.05, < 0.01 respectively). No difference between groups. Reduction in MBL in mefenamic acid group =24%, P < 0.02, and regression to mean of r2 = 0.765, P < 0.01.

10 of 18 in mefenamic acid, and 5 of 16 in etamsylate group reported side effects – nausea, backache, bloated abdomen.

No cessation due to side effects
Funding source: Not reported. Delandale Lab acknowledge.

Study summary: Both treatments effective and perhaps should be used in combination.
Coulter 1995273Systematic review; meta-analysis

EL = 1+
Population characteristics: Searches undertaken on MEDLINE

Country:
Review of evidence for treatment of HMBMBLAntifibrinolytics: Pooled result from 7 trials was a % reduction in MBL of 46.7 (95% CI 47.9–51.6).

Reports on 4 RCT of etamsylate. Meta-analysis identifies a % blood loss reduction of 13.1 (95% CI 10.9–15.3).

Norethisterone: 4 RCTs showed a reduction change in MBL of −3.6% (−6.1, 1.1)

Danazol: 5 RCTs showed a combined reduction in MBL of 49.7% (47.9, 51.6)

IUDs: 4 RCTS showed a combined reduction in MBL of 58.6 (56.7, 60.6)

Mefenamic acid: Pooled results for 10 studies = −29% (95% CI 27.9–30.2). Diclofenac: 2 studies = −26.9% (23.3–30.6). Naproxen: 5 studies = −26.4% (24.6–28.3). Ibuprofen: 3 studies = −16.2% (13.6–18.7).

OCP: 1 RCTMBL reduction = 43%

Side effects not reported.
Funding source: Not stated

Study summary: Studies of this preparation report greater reductions in blood loss but slightly more side effects than mefenamic acid.

From: Evidence Tables

Cover of Heavy Menstrual Bleeding
Heavy Menstrual Bleeding.
NICE Clinical Guidelines, No. 44.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2007 Jan.
Copyright © 2007, National Collaborating Centre for Women's and Children's Health.

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