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Purpose: To evaluate the impact of an interleukin-1 (IL-1) antagonist anakinra (Kineret®) on endometriosis-related quality of life (QoL), pain, and inflammatory biomarkers. Methods: This was a single-site, randomized, double-blinded, placebo-controlled, cross-over pilot clinical study of patients recruited at an academic specialty clinic. Eligible participants were females aged 18– 45 years with menstrual cycles every 24– 32 days. Subjects had moderate to severe dysmenorrhea and either a surgical diagnosis of endometriosis or an endometrioma on imaging. Subjects were randomly assigned in a double-blind fashion to receive either the study drug or placebo administered as daily injections during the first 3 periods and then the alternate intervention for the next 3 periods. Results: Fifteen subjects completed the 6 menstrual cycle study. After each period, they completed the Endometriosis Health Profile-30 (EHP-30) QoL questionnaire and an assessment of dysmenorrhea using a 0– 100 Visual Analogue Scale (VAS). All domains of the EHP-30 showed a trend towards improvement, with significant improvements in powerlessness (54.5 vs 63.3, p = 0.04) and self-image (58.1 vs 66.7, p = 0.03) on the study drug compared to placebo. The mean dysmenorrhea VAS also trended toward improvement with a score of 37.5 during active treatment and 42.6 with placebo (p = 0.26). No difference in menstrual cycle length was detected (29.3 days vs 27.7 days, p = 0.56). There were significant differences in multiple inflammatory biomarkers between the study drug and placebo, including BDNF, IL-1, and IL-6 among certain groups. Conclusion: With all EHP-30 domains and the dysmenorrhea VAS showing either a statistical improvement or trend towards improvement, there is justification for a larger study. As no impact on menstrual cycles was detected, anakinra may be a particularly impactful option for women desiring fertility. Additional evaluation is needed on the role of anakinra on inflammatory markers given significant reductions were identified in multiple biomarkers. Plain Language Summary: Endometriosis is a common gynecologic disease afflicting millions of patients. Anakinra is an IL-1 antagonist currently used for treatment of rheumatoid arthritis which has been found to improve quality of life measures for patients with endometriosis. Anakinra also reduces levels of biomarkers known to be associated with endometriosis-related inflammation. More study is needed on the role of anakinra in improving endometriosis symptoms. [ABSTRACT FROM AUTHOR]

Problem: Estrogen‐dependent extrauterine implantation and growth of menstrual endometrial tissue affects roughly 10% of reproductive age women and depends on suppression of local innate immune defenses to prevent ectopic tissue rejection. Immunohistochemistry has shown the immune check‐point inhibitor CD200 which can suppress rejection is expressed in eutopic endometrium and in ectopic deposits. Soluble CD200 accumulated in venules draining eutopic and ectopic endometrium of endometriosis cases in the secretory phase but not proliferative phase of the menstrual cycle, and should be increased in the circulation. Method of Study: Sera from endometriosis and non‐endometriosis controls were tested by ELISA for CD200. Endometrial CD200, CD200R1 and CD200R2 mRNA in eutopic was quantified by RT‐PCR and localized by in situ hybridization. CD200R1 protein was quantified by immunohistochemistry. Results: Secretory phase serum CD200 was elevated in women with endometriosis compared to controls. Serum CD200 correlated with matched endometrial CD200 mRNA levels. Expression of mRNA for CD200R1 which signals immune suppression was decreased whereas mRNA for the CD200R2 activating receptor was increased. In situ staining of CD200R1 and CD200R2 mRNA showed both receptors were expressed and the fraction of CD200R that is CD200R1 was reduced in secretory and menstrual phase endometriosis endometrium consistent with the RT‐PCR result. By contrast, CD200R1 protein and CD200R1 fraction of total CD200R protein were increased in endometriosis. Conclusions: Failure to suppress circulating CD200 levels in the secretory phase had an 87% specificity and 90% sensitivity for endometriosis. CD200 and increased CD200R1 expression may facilitate development of ectopic deposits by suppressing rejection mechanisms. [ABSTRACT FROM AUTHOR]

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1467-8519.2007.00552.x Byline: SANJAY K. AGARWAL (1), SYLVIA ESTRADA (2), WARREN G. FOSTER (3), L. LEWIS WALL (4), DOUG BROWN (5), ELAINE S. REVIS (6), SUZANNE RODRIGUEZ (7) Keywords: ethics; research; endometriosis; motivation Abstract: ABSTRACT BACKGROUND: The objective of this study was to identify factors motivating women to take part in endometriosis research and to determine if these factors differ for women participating in clinical versus basic science studies. METHODS: A consecutive series of 24 women volunteering for participation in endometriosis-related research were asked to indicate, in their own words, why they chose to volunteer. In addition, the women were asked to rate, on a scale of 0 to 10, sixteen potentially motivating factors. The information was gathered in the form of an anonymous self-administered questionnaire. RESULTS: Strong motivating factors (mean score >8) included potential benefit to other women's health, improvement to one's own condition, and participation in scientific advancement. Weak motivating factors (mean score CONCLUSION: This study is the first study to specifically investigate the factors that motivate women to take part in endometriosis research. Understanding why women choose to take part in such research is important to the integrity of the informed consent process. The factors most strongly motivating women to participate in endometriosis research related to improving personal or public health; the weakest, to financial compensation and pleasing the doctor. Author Affiliation: (1)University of California at San Diego (2)Women's Cancer Research Institute, at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center (3)Centre for Reproductive Care and Reproductive Biology Division at McMaster University (4)Washington University in St. Louis (5)Washington University Medical Center in St. Louis (6)Department of Psychology at Case Western Reserve University in Cleveland, Ohio (7)Cedars-Sinai Medical Center Article note: Sanjay K. Agarwal, MD, FACOG, Department of Reproductive Medicine, UCSD School of Medicine, Basic Science Building #5040, 9500 Gilman Drive, La Jolla, California 92093-0633, Phone: 1-858-534-8930, Fax: 1-858-534-8856. e-mail: skagarwal@ucsd.edu