Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo.

Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue.

[Evaluation of an estrogen vaginal cream for the treatment of dyspareunia: a double-blind randomized trial]. / [Évaluation d'une crème œstrogénique vaginale dans le traitement de la vestibulodynie provoquée : essai randomisé à double insu].

OBJECTIVE: Our objective was to assess the short-term effect of an estrogen cream on symptoms associated with provoked vestibulodynia. METHODS: We undertook a double-blind randomized trial in women who had experienced dyspareunia satisfying the Friedrichcriteria for at least three months. We compared the daily application of 3 g of vaginal cream containing 1.875 g of conjugated estrogens for six weeks (estrogen group) with the application of a comparable cream without estrogens (placebo group). The main outcome was modification of dyspareunia,determined by a visual analogue scale of pain from the pretreatment period to the post-treatment period. Secondary outcomes were colposcopic evaluation of the vulva and pain reported during the swab test. RESULTS: Of 69 women randomized, 61 participated for the full duration of the trial. Dyspareunia was significantly lessened in both groups (estrogen group: 7.4 ± 1.9 pre-treatment vs. 4.8 ± 3.0 post-treatment, P < 0. 01; placebo group:7.1 ± 1.9 vs. 4.9 ± 2. 7, P < 0.01), but the difference observed in terms of decrease between the two groups was not found to be significant (P = 0.5). Alternatively, the group treated with estrogen cream showed (1) a more substantial decrease of the pain reported at the orifices of the Bartholin's glands when palpated with a swab (P < 0.01), and (2) a decrease of the inflammation observed at the orifices of the Bartholin's glands orifices and the posterior fourchette (P < 0.01). CONCLUSION: Applying a vaginal cream, whether it contains estrogens or not, for six weeks lessens dyspareunia. Adding estrogens to such a cream could facilitate a decrease of the inflammation observed at the orifices of the Bartholin's glands and the vestibule.