Selective progesterone receptor modulators (SPRMs) for uterine fibroids

Ally Murji; Lucy Whitaker; Tiffany L Chow; Mara L Sobel

doi:10.1002/14651858.CD010770.pub2

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Respuestas clínicas Cochrane
Guías
Temas

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Topics

Temas

Figure 1

Study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Forest plot of comparison: 1 SPRM versus placebo, outcome: 1.1 Change in symptom severity score (QoL).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Forest plot of comparison: 1 SPRM versus placebo, outcome: 1.2 Change in health‐related quality of life score.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Forest plot of comparison: 1 SPRM versus placebo, outcome: 1.3 Change in menstrual blood loss.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 7

Forest plot of comparison: 2 SPRM versus leuprolide acetate, outcome: 2.1 Change in symptom severity score (QoL).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 8

Forest plot of comparison: 2 SPRM versus leuprolide acetate, outcome: 2.2 Change in health‐related quality of life score.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 9

Forest plot of comparison: 2 SPRM versus leuprolide acetate, outcome: 2.3 Change in menstrual blood loss.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 SPRM versus placebo, Outcome 1 Change in symptom severity score (QoL).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 SPRM versus placebo, Outcome 2 Change in health‐related quality of life score.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 SPRM versus placebo, Outcome 3 Change in menstrual blood loss.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 SPRM versus placebo, Outcome 4 Amenorrhoea.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 SPRM versus placebo, Outcome 5 Change in uterine volume.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 SPRM versus placebo, Outcome 6 SPRM‐associated endometrial changes.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 SPRM versus leuprolide acetate, Outcome 1 Change in symptom severity score (QoL).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 SPRM versus leuprolide acetate, Outcome 2 Change in health‐related quality of life score.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 SPRM versus leuprolide acetate, Outcome 3 Change in menstrual blood loss.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.4

Comparison 2 SPRM versus leuprolide acetate, Outcome 4 Amenorrhoea.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.5

Comparison 2 SPRM versus leuprolide acetate, Outcome 5 Change in pelvic pain.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.6

Comparison 2 SPRM versus leuprolide acetate, Outcome 6 Percent change in uterine volume.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.7

Comparison 2 SPRM versus leuprolide acetate, Outcome 7 SPRM‐associated endometrial changes.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. SPRM versus placebo

SPRM vs placebo
Patient or population: women with uterine fibroids Setting: outpatient clinic Intervention: SPRM Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with placebo	Risk with SPRM	Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Quality of life: change in symptom severity score measured with Uterine Fibroid Symptom Quality of Life Scale (UFS‐QoL): scale 0 to 100		Mean change in symptom severity score (QoL) in the intervention group was 20.04 points lower (26.63 lower to 13.46 lower), indicating improvement in symptom severity with SPRM treatment for 3 months	‐	171 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a
Quality of life: change in health‐related quality of life score measured with UFS‐QoL: scale 0 to 100		Mean change in health‐related quality of life score in the intervention group was 22.52 points higher (12.87 higher to 32.17 higher), indicating improvement in quality of life with SPRM treatment for 3 to 6 months	‐	200 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	1 RCT (Fiscella 2006) reported outcomes at 6 months. Remaining studies had a 3‐month follow‐up period
Abnormal uterine bleeding: change in menstrual blood loss		Mean change in menstrual blood loss in the intervention group was 1.11 points lower (1.38 lower to 0.83 lower), indicating a decrease in menstrual blood loss with SPRM treatment for 3 months	‐	310 (3 RCTs)	⊕⊕⊕⊝ MODERATE^a	Measured by PBAC score or similar menstrual pictorial score. PBAC score ≥ 100 correlates with menorrhagia, which is defined as > 80 mL menstrual blood loss
Abnormal uterine bleeding: amenorrhoea	29 per 1000	477 per 1000 (237 to 961) with 3 to 6 months of SPRM treatment	OR 82.50 (37.10 to 183.90)	590 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a	1 RCT (Fiscella 2006) reported outcomes at 6 months. Remaining studies had a 3‐month follow‐up period
Pelvic pain (measured subjectively)		No conclusions could be drawn owing to variability in estimates		629 (7 RCTs)
Adverse effects: SPRM‐associated endometrial changes	77 per 1000	351 per 1000 (176 to 697) with 3 months of SPRM treatment	OR 15.12 (6.45 to 35.47)	405 (5 RCTs)	⊕⊕⊝⊝ LOW^a,b
*Risk in the intervention group (and its 95% confidence interval) is based on mean risk in the comparison group and relative effect of the intervention (and its 95% CI) CI: confidence interval; OR: odds ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to the estimate of effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of effect but may be substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^aDowngraded one level as publication bias suspected because no small negative studies included. Also, many studies were conducted and not published ^bDowngraded one level because of serious issues with indirectness of evidence when criteria for evaluating endometrial specimens differed between studies

Summary of findings for the main comparison. SPRM versus placebo

Ir a la tabla de la revisión

Summary of findings 2. SPRM versus leuprolide acetate for uterine fibroids

SPRM versus leuprolide acetate for uterine fibroids
Patient or population: uterine fibroids Setting: outpatient clinic Intervention: SPRM Comparison: leuprolide acetate
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with leuprolide acetate	Risk with SPRM	Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Quality of life: change in symptom severity score measured with Uterine Fibroid Symptom Quality of Life Scale (UFS‐QoL): scale 0 to 100		Mean change in symptom severity score (QoL) in the SPRM group was 3.7 points lower (9.85 lower to 2.45 higher) compared with the leuprolide group at 3 months	‐	281 (1 RCT)	⊕⊕⊕⊝ MODERATE^a
Quality of life: change in health‐related quality of life score measured with UFS‐QoL: scale 0 to 100		Mean change in health‐related quality of life score in the SPRM group was 1.06 points higher (5.73 lower to 7.85 higher) compared with the leuprolide group at 3 months	‐	281 (1 RCT)	⊕⊕⊕⊝ MODERATE^a
Abnormal uterine bleeding: change in menstrual blood loss (measured using PBAC score)		Mean change in menstrual blood loss in the SPRM group was 6 points higher (40.95 lower to 52.95 higher) compared with the leuprolide group at 3 months	‐	281 (1 RCT)	⊕⊕⊝⊝ LOW^a,b	PBAC score ≥ 100 correlates with menorrhagia, which is defined as > 80 mL menstrual blood loss
Abnormal uterine bleeding: amenorrhoea	804 per 1000	828 per 1000 (732 to 933) at 3 months	OR 1.14 (0.60 to 2.16)	280 (1 RCT)	⊕⊕⊕⊝ MODERATE^a
Pelvic pain (measured using McGill Pain Questionnaire: range 0 to 45)		Mean change in pelvic pain in the SPRM group was 0.01 points lower (2.14 lower to 2.12 higher) than in the leuprolide group at 3 months	‐	281 (1 RCT)	⊕⊕⊕⊝ MODERATE^a
Adverse effects: SPRM‐associated endometrial changes	119 per 1000	585 per 1000 (340 to 1000) after 3 months of treatment	OR 10.45 (5.38 to 20.33)	301 (1 RCT)	⊕⊕⊕⊝ MODERATE^a
*Risk in the intervention group (and its 95% confidence interval) is based on mean risk in the comparison group and relative effect of the intervention (and its 95% CI) CI: confidence interval; OR: odds ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to the estimate of effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of effect but may be substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^aDowngraded one level as publication bias strongly suspected ^bDowngraded one level owing to serious issue with imprecision as point estimate has very wide confidence interval

Summary of findings 2. SPRM versus leuprolide acetate for uterine fibroids

Ir a la tabla de la revisión

Table 1. Mifepristone studies

Study	Participants	Daily dose	Control	Follow‐up (months)
Esteve 2013	124	5 mg	Placebo	3
Fiscella 2006	42	5 mg	Placebo	6
Bagaria 2009	40	10 mg	Placebo	3
Liu 2015	62	10 mg	Placebo	3
Prasad 2013	132	10 mg	Placebo	3
Reinsch 1994	14	25 mg	Leuprolide acetate	3
Engman 2009	30	50 mg	Vitamin B	3

Table 1. Mifepristone studies

Ir a la tabla de la revisión

Table 2. Ulipristal acetate studies

Study	Participants	Daily dose	Control	Follow‐up (months)
Bigatti 2014	Unknown	5 mg	No treatment	Not stated
Donnez 2012	242	5 or 10 mg	Placebo	3
Donnez 2012a	303	5 or 10 mg	Leuprolide acetate	3
Levens 2008	22	10 or 20 mg	Placebo	3
Nieman 2011	42	10 or 20 mg	Placebo	3

Table 2. Ulipristal acetate studies

Ir a la tabla de la revisión

Table 3. Asoprisnil studies

Study	Participants	Daily dose	Control	Follow‐up (months)
Chwalisz 2007	129	5 or 10 or 25 mg	Placebo	3
Wilkens 2008	33	10 or 25 mg	Placebo	3

Table 3. Asoprisnil studies

Ir a la tabla de la revisión

Table 4. Change in fibroid volume: SPRM versus placebo

Study	SPRM type	SPRM			Placebo
		MD	SD	n	MD	SD	n	Finding
Bagaria 2009	Mifepristone	‐41.5 cc	220.59	19	0.6 cc	266.63 cc	16	No significant difference
Engman 2009	Mifepristone	‐10.0 cc	107.39	12	‐16.0 cc	98.54 cc	15	No significant difference
Esteve 2013	Mifepristone	‐37.0 cc	96.24	58	4.0 cc	99.1 cc	47	Favours SPRM
Donnez 2012	Ulipristal acetate	‐16.88%	31.34	165	3.0%	31.63	45	Favours SPRM
Nieman 2011	Ulipristal acetate	‐20.5%	20.6	26	7.0%	25.0	12	Favours SPRM
cc: cubic centimetres MD: mean difference n: fibroids tracked SD: standard deviation

Table 4. Change in fibroid volume: SPRM versus placebo

Ir a la tabla de la revisión

Table 5. Change in fibroid volume (%): SPRM versus leuprolide

Study	SPRM			Leuprolide
	MD	SD	n	MD	SD	n	Finding
Donnez 2012a	‐39.03%	37.92	188	‐53.0%	24.44	93	Favours leuprolide
MD: mean difference n: fibroids tracked SD: standard deviation

Table 5. Change in fibroid volume (%): SPRM versus leuprolide

Ir a la tabla de la revisión

Comparison 1. SPRM versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in symptom severity score (QoL) Show forest plot	4	171	Mean Difference (IV, Random, 95% CI)	‐20.04 [‐26.63, ‐13.46]

2 Change in health‐related quality of life score Show forest plot	4	200	Mean Difference (IV, Random, 95% CI)	22.52 [12.87, 32.17]

3 Change in menstrual blood loss Show forest plot	3	310	Std. Mean Difference (IV, Random, 95% CI)	‐1.11 [‐1.38, ‐0.83]

4 Amenorrhoea Show forest plot	7	590	Odds Ratio (IV, Random, 95% CI)	82.50 [37.01, 183.90]

5 Change in uterine volume Show forest plot	4	419	Std. Mean Difference (IV, Random, 95% CI)	‐0.63 [‐0.91, ‐0.36]

6 SPRM‐associated endometrial changes Show forest plot	5	405	Odds Ratio (IV, Random, 95% CI)	15.12 [6.45, 35.47]

Comparison 1. SPRM versus placebo

Ir a la tabla de la revisión

Comparison 2. SPRM versus leuprolide acetate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in symptom severity score (QoL) Show forest plot	1	281	Mean Difference (IV, Random, 95% CI)	‐3.70 [‐9.85, 2.45]

2 Change in health‐related quality of life score Show forest plot	1	281	Mean Difference (IV, Random, 95% CI)	1.06 [‐5.73, 7.85]

3 Change in menstrual blood loss Show forest plot	1	281	Mean Difference (IV, Random, 95% CI)	6.00 [‐40.95, 52.95]

4 Amenorrhoea Show forest plot	1	280	Odds Ratio (M‐H, Random, 95% CI)	1.14 [0.60, 2.16]

5 Change in pelvic pain Show forest plot	1	281	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐2.14, 2.12]

6 Percent change in uterine volume Show forest plot	2	295	Mean Difference (IV, Random, 95% CI)	25.94 [20.49, 31.39]

7 SPRM‐associated endometrial changes Show forest plot	1	301	Odds Ratio (M‐H, Random, 95% CI)	10.45 [5.38, 20.33]

Comparison 2. SPRM versus leuprolide acetate

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet