Scolaris Content Display Scolaris Content Display

Study flow diagram.
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Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

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

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

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

Forest plot of comparison: 1 SPRM versus placebo, outcome: 1.1 Change in symptom severity score (QoL).
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Figure 4

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

Forest plot of comparison: 1 SPRM versus placebo, outcome: 1.2 Change in health‐related quality of life score.
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Figure 5

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

Forest plot of comparison: 1 SPRM versus placebo, outcome: 1.3 Change in menstrual blood loss.
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Figure 6

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

Forest plot of comparison: 2 SPRM versus leuprolide acetate, outcome: 2.1 Change in symptom severity score (QoL).
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Figure 7

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

Forest plot of comparison: 2 SPRM versus leuprolide acetate, outcome: 2.2 Change in health‐related quality of life score.
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Figure 8

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

Forest plot of comparison: 2 SPRM versus leuprolide acetate, outcome: 2.3 Change in menstrual blood loss.
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Figure 9

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

Comparison 1 SPRM versus placebo, Outcome 1 Change in symptom severity score (QoL).
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Analysis 1.1

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

Comparison 1 SPRM versus placebo, Outcome 2 Change in health‐related quality of life score.
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Analysis 1.2

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

Comparison 1 SPRM versus placebo, Outcome 3 Change in menstrual blood loss.
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Analysis 1.3

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

Comparison 1 SPRM versus placebo, Outcome 4 Amenorrhoea.
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Analysis 1.4

Comparison 1 SPRM versus placebo, Outcome 4 Amenorrhoea.

Comparison 1 SPRM versus placebo, Outcome 5 Change in uterine volume.
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Analysis 1.5

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

Comparison 1 SPRM versus placebo, Outcome 6 SPRM‐associated endometrial changes.
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Analysis 1.6

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

Comparison 2 SPRM versus leuprolide acetate, Outcome 1 Change in symptom severity score (QoL).
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Analysis 2.1

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

Comparison 2 SPRM versus leuprolide acetate, Outcome 2 Change in health‐related quality of life score.
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Analysis 2.2

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

Comparison 2 SPRM versus leuprolide acetate, Outcome 3 Change in menstrual blood loss.
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Analysis 2.3

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

Comparison 2 SPRM versus leuprolide acetate, Outcome 4 Amenorrhoea.
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Analysis 2.4

Comparison 2 SPRM versus leuprolide acetate, Outcome 4 Amenorrhoea.

Comparison 2 SPRM versus leuprolide acetate, Outcome 5 Change in pelvic pain.
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Analysis 2.5

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

Comparison 2 SPRM versus leuprolide acetate, Outcome 6 Percent change in uterine volume.
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Analysis 2.6

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

Comparison 2 SPRM versus leuprolide acetate, Outcome 7 SPRM‐associated endometrial changes.
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Analysis 2.7

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

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

Risk with placebo

Risk with SPRM

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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊝⊝
LOWa,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

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Summary of findings for the main comparison. SPRM versus placebo
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

Risk with leuprolide acetate

Risk with SPRM

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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊕⊝
MODERATEa

*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

Figures and Tables -
Summary of findings 2. SPRM versus leuprolide acetate for uterine fibroids
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

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Table 1. Mifepristone studies
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

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Table 2. Ulipristal acetate studies
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

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Table 3. Asoprisnil studies
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

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Table 4. Change in fibroid volume: SPRM versus placebo
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

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

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Comparison 1. SPRM versus placebo
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]

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Comparison 2. SPRM versus leuprolide acetate