Tranexamic acid for the treatment of heavy menstrual bleeding: efficacy and safety

Figures & data

Table 1 Tranexamic acid in the treatment of heavy menstrual bleeding

Trial	Intervention method	n	Selection criteria	Outcome measures	Main results
Andersch et al^Citation23	1. TA 1.5 g × 3 pd 1–3 and 1 g × 2 pd 4–7	15	Women aged 34–49 years MBL > 80 mL per cycle	MBL (AHM) Duration of bleeding	Mean MBL change from baseline: TA −53%c and FLU −24%,c P < 0.01 No effect on duration of bleeding Discontinuation: 0%
	2. FLU 100 mg × 2 pd 1–5	15	Regular cycle
	Total	15
	Duration: 2 screening and 2 + 2 treatment cycles Randomized open cross-over study Method of randomization unclear
Bonnar and Sheppard^Citation24	1. ETM 500 mg × 4 pd 1–5	27	Women aged 35–46 years	MBL (AHM)	Mean MBL change from baseline: ETM +3%, TA −54%,e and MEF −20%,e P < 0.05 TA compared with MEF, P < 0.001 TA compared with ETM No effect on duration of bleeding Reduction in the number of napkins used: P < 0.01 TA compared with baseline Discontinuation: ETM 41%, TA 15%, and MEF 13%
	2. TA 1 g × 4 pd 1–5	26	MBL > 80 mL per cycle	Duration of bleeding
	3. MEF 500 mg × 3 pd 1–5	23	Normal hysteroscopy, endometrial biopsy, and cervical cytology	Number of sanitary napkins used
	Total	76
	Duration: 3 placebo and 3 treatment cycles Randomization by computer-generated list to one of three groups Blinding unclear
Callender et al^Citation25	1. TA 1 g × 4 pd 1–4	20	Women aged 33–48 years	MBL (Total body counter)	Mean MBL change from baseline: TA −36%b and placebo −6%, P < 0.05 No effect on duration of bleeding Reduction in the number of napkins used: P < 0.01 TA compared with placebo Discontinuation: 20%
	2. Placebo pd 1–4	20	Subjectively perceived menorrhagia or iron deficiency anemia
	Total	20		Duration of bleeding
	Duration: 3 + 3 treatment cycles Randomized double-blind cross-over study			Number of napkins used
Freeman et al^Citation26	1. TA 650 mg × 3 pd 1–5	115	Women aged 18–49 years	MBL (AHM)	Mean MBL change from baseline: TA low dose −26%, TA high dose −39%, and placebo −2%, P < 0.0001 both TA groups compared with placebo QOL: improvements in limitations in social/leisure activities, and physical activities in both TA groups compared with placebo (P ≤ 0.0055) Discontinuation: TA lower dose 9%, TA higher dose 13%, and placebo 9%
	2. TA 1.3 g × 3 pd 1–5	112	Average MBL ≥ 80 mL over two cycles	QOL (MIQ)
	3. Placebo pd 1–5	67		Number of large stains
	Total	294	Regular cycle
	Duration: 2 screening and 3 treatment cycles Randomized double-blind placebo-controlled study		Uterine fibroids not excluded unless surgical management warranted
Kouides et al^Citation27	1. TA 1 g × 4 pd 1–5	67	Women aged 18–50 years	MBL (PBAC)	Mean MBL (PBAC) change from baseline: TA −38% and IN-DDAVP −23%, P = 0.0002 QOL: improved in both groups (significantly on RUTA scale) Discontinuation: 43% IN-DDAVP→TA and 33% TA→ IN-DDAVP
	2. IN-DDAVP 300 μg × 1 pd 2–3	49	Abnormal laboratory hemostasis	QOL (HRQOL, SF-36, CES-D, and RUTA)
	Total	116
	Duration: 2 + 2 treatment cycles Randomized open cross-over study Method of randomization unclear		PBAC score ≥ 100 Regular cycle Uterine fibroids not excluded if uterus <12 weeks gestational size
Kriplani et al^Citation28	1. TA 500 mg × 4 pd 1–5	49	Women presenting with heavy	MBL (PBAC)	Mean MBL (PBAC) change from baseline: TA −60%d and MPA −58%d Duration of bleeding decreased in both groups (P < 0.005) Hemoglobin increased in both groups (TA, P = 0.003; MPA, P = 0.019) Discontinuation: TA 4% and MPA 27%
	2. MPA 10 mg × 2 pd 5–25	45	menstrual bleeding	Duration of bleeding
	Total	94	PBAC score > 100	Hemoglobin
	Duration: 3 months of treatment and 3 months of follow-up Randomized open study			QOL (VAS)
Lukes et al^Citation29	1. 1.3 g × 3 pd 1–5	115	Women aged 18−49 years	MBL (AHM)	Mean MBL change from baseline: TA −40% and placebo −8%, P < 0.001 QOL: improvements in limitations in social/leisure activities and physical activities, work inside and outside the home, and self-perceived MBL compared with placebo (P < 0.001) No significant increase in hemoglobin Discontinuation: TA 24% and placebo 26%
	2. Placebo pd 1–5	72	Average MBL ≥ 80 mL over two cycles	QOL (MIQ)
	Total	187		Number of large stains
	Duration: 2 screening and 6 treatment cycles Randomized double-blind placebo-controlled study		Regular cycle Uterine fibroids not excluded unless surgical management warranted	Hemoglobin and ferritin
Milsom et al^Citation30	1. LNG-IUS (release of 20 μg/day)	16	Women aged 31−49 years	MBL (AHM)	Mean MBL change from baseline: LNG-IUS −83%e at 3 months, −88%e at 6 months, and −96%e at 12 months, FLU −24%,a and TA −47%,c P < 0.001 LNG-IUS compared with FLU, P < 0.01 LNG-IUS compared with TA, P < 0.05 TA compared with FLU Hemoglobin increase: LNG-IUS 10%, FLU 0%, and TA 0%
	2. FLU 100 mg × 2 pd 1–5	15	MBL > 80 mL per cycle	Hemoglobin
	3. TA 1.5 g × 3 pd 1–3 and 1 g × 2 pd 4–5	15	Regular cycle
	Total	15
	LNG-IUS 12 months open-label, then randomization to non-blind treatment (FLU and TA) for 2 + 2 cycles in cross-over fashion Method of randomization unclear
Nilsson and Rybo^Citation31	1. TA 250 mg × 6 pd 1–4 and 500 mg × 6 pd 1–4		Women aged 15–49 years Subjectively perceived menorrhagia	MBL (AHM)	Mean MBL change from baseline: TA −38% (total dose of 12 g per cycle) and −51% (total dose of 24 g per cycle) Discontinuation: 0%
	2. TA 500 mg × 6 pd 1–4 and 1 g × 6 hourly pd 1–4
	3. Placebo × 6 pd 1–4
	Total	36
	Duration: 2 screening and 1 + 1 + 1 treatment cycles Randomized double-blind cross-over study Method of randomization unclear Only one cycle of treatment on each dosage
Preston et al^Citation32	1. TA 1 g × 4 pd 1–4	25	Age 18 years or more	MBL (AHM)	Mean MBL change from baseline: TA −45%f and NOR +20% Reduced flooding/leakage and improved sex life in TA-group Discontinuation: 0%
	2. NOR 5 mg × 2 pd 19–26	21	Average MBL > 80 mL over two cycles	QOL (using 5-point scale)
	Total	46
	Duration: 2 placebo and 2 treatment cycles Randomized double-blind placebo-controlled study		Regular cycle Confirmed to be ovulating
Vermylen et al^Citation33	1. TA 500 mg × 6 starting from pd 1 until bleeding stops	22	Subjectively perceived menorrhagia	MBL (mean hemoglobin loss from sanitary napkins)	Mean MBL reduction 35% in TA-group No effect on duration of bleeding No reduction in the number of napkins used Discontinuation: 27%
	2. Placebo × 6 starting from pd 1 until bleeding stops	22
	Total			Duration of bleeding
	Randomized double-blind cross-over study	22		Number of sanitary napkins used

Notes:

a P < 0.05;

b P < 0.02;

c P < 0.01;

d P < 0.005;

e P < 0.001;

f P < 0.0001.

Abbreviations: AHM, alkaline hematin method; CES-D, Center for Epidemiologic Studies Depression Scale; ETM, etamsylate; FLU, flurbiprofen; HRQOL, Health-Related Quality of Life; IN-DDAVP, intranasal desmopressin; IUCD, intrauterine copper device; IUD, intrauterine device; LNG-IUS, levonorgestrel-releasing intrauterine system; MBL, menstrual blood loss; MEF, mefenamic acid; MIQ, Menorrhagia Impact Questionnaire; MPA, medroxyprogesterone acetate; NOR, norethisterone; OC, oral contraceptive; PBAC, Pictorial Blood loss Assessment Chart; pd, period day; QOL, quality of life; RUTA, Modified Ruta Menorrhagia Severity Scale; SF-36, Short Form-36; TA, tranexamic acid; VAS, visual analog scale.

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