Hudelist 2007.

Study characteristics
Patient sampling	Primary objective: to analyse the expression of both aromatase and EST in the uterine and ectopic endometrium of patients with endometriosis Participants: women undergoing surgery for suspected endometriosis or non‐malignant conditions (e.g. fibroids) Selection criteria: exclusion criteria: history of PID, malignancy, adenomyosis uteri, intake of GnRH agonists, or exposure to steroids within the 6/12 months prior to surgery Study design: observational two‐gate, prospective collection of samples
Patient characteristics and setting	Clinical presentation: pain ‐ 26/35 and infertility ‐ 9/35, endometriosis; controls ‐ not specified Age: median age 39.6 years, endometriosis; 37.8 years, controls Number enrolled: 68 women Number available for analysis: 68 women (38 in proliferative and 27 in secretory cycle phase) Setting: Division of Special Gynecology, University of Vienna and LKH Villach hospital Place of study: Villach and Vienna, Austria Period of study: 2002‐2005 Language: English
Index tests	Index test: aromatase and EST Description of positive case definition by index test as reported: the expression was quantified by immunoreactive score (IRS), defined by IHC stain intensity: IRS > 8 ‐ strong immunoreactivity; > 4 and ≤ 8 ‐ moderate; > 0 and ≤ 4 ‐ weak, 0 ‐ negative; laboratory techniques described; no threshold provided Examiners: independent blinded assessment by 2 pathologists Interobserver variability: not reported; decision by consensus
Target condition and reference standard(s)	Target condition: endometriosis Prevalence of target condition in the sample: n/N = 35/68 (40%) (all stage I‐II); controls 33 Reference standard: laparoscopy/laparotomy Description of positive case definition by reference test as reported: visual inspection, AFS classification Examiners: no information provided
Flow and timing	Time interval between index test and reference standard: eutopic tissue specimens were obtained at surgery Withdrawals: none reported
Comparative
Notes	Conclusion: The elevated expression of aromatase in eutopic and ectopic endometrium from patients with endometriosis in the presence of comparable EST provides further evidence for unopposed local biosynthesis of estrogens in endometriosis. Comments: For aromatase the data is presented only for glandular cells, diagnostic threshold defined by the review authors as presence or absence of expression; there was no statistically significant difference between the groups in the overall uterine endometrium (not presented) For EST there was no statistically significant difference between the groups ‐ no data available for meta‐analysis (Appendix 7)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Did the study avoid inappropriate exclusions?	Yes
Was a 'two‐gate' design avoided?	No
		High	High
DOMAIN 2: Index Test All tests
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	No
Was a menstrual cycle phase considered in interpreting the index test	Yes
		High	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
		Unclear	Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Low