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Meta-Analysis
. 2012 Mar 14;2012(3):CD002122.
doi: 10.1002/14651858.CD002122.pub2.

Progestagens and anti-progestagens for pain associated with endometriosis

Julie Brown  1 , Sari Kives, Muhammad Akhtar
Affiliations
Meta-Analysis

Progestagens and anti-progestagens for pain associated with endometriosis

Julie Brown et al. Cochrane Database Syst Rev. .

Abstract

Background: Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of reproductive age and may present as pain or infertility. The pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain. Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis. Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices.

Objectives: To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis.

Search methods: We used the search strategy of the Menstrual Disorders and Subfertility Group to identify all publications which described or might have described randomised controlled trials (RCTs) of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. We updated the review in 2011.

Selection criteria: We considered only RCTs which compared the use of progestagens and anti-progestagens with other interventions, placebo or no treatment for the alleviation of symptomatic endometriosis.

Data collection and analysis: We have added six new studies, bringing the total of included studies to 13 in the update of this review. The six newly included studies evaluated progestagens (comparisons with placebo, danazol, oral or subdermal contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing hormone (GnRH) analogue and other drugs). The remaining studies compared the anti-progestagen gestrinone with danazol, GnRH analogues or itself.

Main results: The progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of significantly more cases of acne (six versus one) and oedema (11 versus one) in the medroxyprogesterone acetate group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo.There was no evidence of a benefit with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects.There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups.There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006).

Authors' conclusions: There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis.

PubMed Disclaimer

Conflict of interest statement

AJD was partly employed on a non‐conditional educational grant from Zeneca Pharma. The grant was utilised to provide a telephone support line for endometriosis patients attending a tertiary specialist clinic.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Forest plot of comparison: 1 Progestagen versus placebo, outcome: 1.3 Patient assessed efficacy, 4 point verbal rating scale at end of treatment (6 months).
4
4
Forest plot of comparison: 1 Progestagen versus placebo, outcome: 1.4 Patient assessed efficacy, 4 point verbal rating scale at end of follow‐up (12 months).
5
5
Forest plot of comparison: 1 Progestagen versus placebo, outcome: 1.5 Change in pain score at 12 months follow‐up (Improvement).
6
6
Forest plot of comparison: 1 Progestagen versus placebo, outcome: 1.2 AFS score (improved or remission).
7
7
Forest plot of comparison: 1 Progestagen versus placebo, outcome: 1.6 Side effects.
8
8
Forest plot of comparison: 2 Depot progestagen versus other treatment, outcome: 2.2 Improvement in symptoms.
9
9
Forest plot of comparison: 2 Depot progestagen versus other treatment, outcome: 2.3 Side effects.
10
10
Forest plot of comparison: 3 Oral progestagens versus other treatment, outcome: 3.1 Patient assessed efficacy (6 months).
11
11
Forest plot of comparison: 3 Oral progestagens versus other treatment, outcome: 3.3 Objective efficacy at end of follow‐up (12 months).
12
12
Forest plot of comparison: 4 Anti‐progestagen versus other treatment, outcome: 4.1 Patient assessed efficacy at end of treatment (6 months).
13
13
Forest plot of comparison: 4 Anti‐progestagen versus other treatment, outcome: 4.3 Objective assessment of efficacy at end of treatment (6 months).
14
14
Forest plot of comparison: 4 Anti‐progestagen versus other treatment, outcome: 4.4 Patient assessed efficacy at end of treatment (6 months).
15
15
Forest plot of comparison: 4 Anti‐progestagen versus other treatment, outcome: 4.5 Patient assessed efficacy at end of follow‐up (12 months).
1.1
1.1. Analysis
Comparison 1 Progestagen versus placebo , Outcome 1 AFS score .
1.2
1.2. Analysis
Comparison 1 Progestagen versus placebo , Outcome 2 AFS score (improved or remission) .
1.3
1.3. Analysis
Comparison 1 Progestagen versus placebo , Outcome 3 Patient assessed efficacy, 4 point verbal rating scale at end of treatment (6 months).
1.4
1.4. Analysis
Comparison 1 Progestagen versus placebo , Outcome 4 Patient assessed efficacy, 4 point verbal rating scale at end of follow‐up (12 months).
1.5
1.5. Analysis
Comparison 1 Progestagen versus placebo , Outcome 5 Change in pain score at 12 months follow‐up (Improvement).
1.6
1.6. Analysis
Comparison 1 Progestagen versus placebo , Outcome 6 Side effects.
2.2
2.2. Analysis
Comparison 2 Depot progestagen versus other treatment, Outcome 2 Improvement in symptoms.
2.3
2.3. Analysis
Comparison 2 Depot progestagen versus other treatment, Outcome 3 Side effects.
3.1
3.1. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 1 Patient assessed efficacy (6 months).
3.2
3.2. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 2 Patient assessed efficacy, 4 point verbal rating scale at end of follow‐up (12 months).
3.3
3.3. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 3 Objective efficacy at end of follow‐up (12 months).
3.4
3.4. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 4 Improved VAS score.
3.5
3.5. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 5 Quality of life.
3.6
3.6. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 6 Severe/very severe signs and symptoms (24 weeks).
3.7
3.7. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 7 Change in pain from baseline to 24 weeks.
3.11
3.11. Analysis
Comparison 3 Oral progestagens versus other treatment, Outcome 11 Side effects.
4.1
4.1. Analysis
Comparison 4 Anti‐progestagen versus other treatment, Outcome 1 Patient assessed efficacy at end of treatment (6 months).
4.2
4.2. Analysis
Comparison 4 Anti‐progestagen versus other treatment, Outcome 2 Patient assessed efficacy 6 months after the end of treatment.
4.3
4.3. Analysis
Comparison 4 Anti‐progestagen versus other treatment, Outcome 3 Objective assessment of efficacy at end of treatment (6 months).
4.4
4.4. Analysis
Comparison 4 Anti‐progestagen versus other treatment, Outcome 4 Patient assessed efficacy at end of treatment (6 months).
4.5
4.5. Analysis
Comparison 4 Anti‐progestagen versus other treatment, Outcome 5 Patient assessed efficacy at end of follow‐up (12 months).
4.6
4.6. Analysis
Comparison 4 Anti‐progestagen versus other treatment, Outcome 6 Side effects.
5.1
5.1. Analysis
Comparison 5 Antiprogestagens (varying dosage), Outcome 1 Subjective improvement in pain.
5.2
5.2. Analysis
Comparison 5 Antiprogestagens (varying dosage), Outcome 2 Objective efficacy ‐ rAFS scores at 6 months.
5.3
5.3. Analysis
Comparison 5 Antiprogestagens (varying dosage), Outcome 3 Side effects.
See this image and copyright information in PMC

Update of

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