Methods

Trial design: 2 period, 4 treatment cross over trial
Country of principal investigators: Finland
Where trial conducted: Finland
Date of trial: not clear
Single Centre
Funder: Medica Ltd (drugs); Yryo Jahnsson Foundation (finance)
Blinding: double blind
Lost to follow‐up: 6 (for reasons unknown)

Participants

Inclusion criteria: Women with symptomatic endometriosis (stage and severity not described). Women were diagnosed by laparoscopy (n=13) and by pelvic examination (n=5)
Exclusion criteria: not clear
No. randomized: 24
No. analysed: 18
Age: mean=33 (22‐43)
Sex: Female
Ethnicity: not known
Social class: not known

Interventions

Group 1 (Indomethacin was given for 2 menstrual cycles then crossover to acetylsalicylic acid, tolfenamic acid and placebo for 2 menstrual cycles each)
No. randomized: 6
No. analysed: not clear
Type of NSAID: Indomethacin
Dose of NSAID: 25 mg
Frequency of dose: 3 x per day
Duration of treatment: 2 menstrual cycles
Additional interventions: none

Group 2 (Acetylsalicylic acid was given for 2 menstrual cycles then crossover to tolfenamic acid, placebo and indomethacin for 2 menstrual cycles each)
No. randomized: 6
No. analysed: not clear
Type of NSAID: Acetylsalicylic
Dose of NSAID: 500 mg
Frequency of dose: 3 x per day
Duration of treatment: 2 menstrual cycles
Additional interventions: none

Group 3 ( Tolfenamic acid was given for 2 menstrual cycles then crossover to placebo, indomethacin and acetylsalicylic acid, for 2 menstrual cycles each)
No. randomized: 6
No. analysed: not clear
Type of NSAID: Tolfenamic acid
Dose of NSAID: 200 mg
Frequency of dose: 3 x per day
Duration of treatment: 2 menstrual cycles
Additional interventions: none

Group 4 (Placebo was given for 2 menstrual cycles then crossover to indomethacin, acetylsalicylic acid and tolfenamic acid for 2 menstrual cycles each)
No. randomized: 6
No. analysed: not clear
Type of drug: Placebo
Frequency of dose: 3 x per day
Duration of treatment: 2 menstrual cycles
Additional interventions: none

Outcomes

These were self‐reported using a questionnaire completed by the patient immediately after each menstrual cyclePain relief: pelvic pain, lower back pain, pain in walking, dyspareunia, pain on defecation, headache; number not reported but described more common with placebo and indomethacin
Quality of life: not reported
Effect on daily activities: not reported
Absence from work or school: not reported
Unintended effects from treatment: gastro‐intestinal complaints (nausea and vomiting); number not reported but described as more common with indomethacin. Psychic complaints (insomnia and nervousness); number not reported but described as more common with indomethacin
No. of women requiring more invasive treatment: not reported
Requirements for additional medication: not reported
Patient satisfaction with treatment: not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Trial design: 2 period, 2 treatment cross over trial
Country of principal investigators: Finland
Where trial conducted: Finland
Date of trial: not clear
Single centre trial
Funder: not clear
Blinding: double blind
Lost to follow‐up: 4 (1 pregnant, 1 had psychiatric problems, and 2 lost for unknown reasons).

Participants

Inclusion criteria: women with endometriosis classified by the American Fertility Society (mild endometriosis n=7; moderate endometriosis n=8; severe endometriosis n=6). Women were diagnosed by pelvic examination, history of menstrual distress and by direct visualisation of pelvic regions at laporoscopy or laparatomy
Exclusion criteria: not clear
No. randomized: 24
No. analysed: 20
Age: Group 1 mean=32, Group 2 mean=35
Sex: Female
Ethnicity: not known
Social class: not known

Interventions

Group 1 (Naproxen Sodium ‐ NSAID ‐ was given for 2 menstrual cycles, then crossover to placebo for 2 menstrual cycles)
No. randomized: 12
No. analysed: 11
Type of NSAID: Naproxen sodium
Dose of NSAID: 275mg tablets,
Frequency of dose: 1 ‐ 2 tablets 4 x per day
Duration of treatment: 2 menstrual cycles
Additional interventions: additional analgesia was allowed if no relief after the first two doses of NSAID

Group 2 (Placebo was given for 2 menstrual cycles, then crossover to Naproxen Sodium ‐ NSAID ‐ for 2 menstrual cycles)
No. randomized: 12
No. analysed: 9
Type of drug: placebo
Frequency of dose: 1 ‐ 2 tablets, 4 x per day
Duration of treatment: two menstrual cycles
Additional interventions: additional analgesia was allowed if no relief after first two doses

Outcomes

These were all self‐reported using a questionnaire completed by the patient immediately after each menstrual cycle.

Pain relief: measured after each menstrual cycle (score 3 to ‐1)
Quality of life: not reported
Effect on daily activities: activity of patient (score 4 to 0)
Absence from work or school: not reported
Unintended effects from treatment: fatigue, lightheadedness, eye lid edema, and chest pain (n=4 while taking Naproxen Sodium). Hypomenorrhea, diarrhea, increases diuresis, headache, epigastric pain, nausea and vomiting, and tremor and dizziness (n=7 while taking placebo).
No. of women requiring more invasive treatment: not reported
Requirements for additional medication: supplemental analgesia was more common in the placebo group (14) than in the NSAID group (2).
Patient satisfaction with treatment: not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear