Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9) on the Upper Female Reproductive Tract: A Randomized Crossover Study

摘要: Intravaginal anti-HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract might contribute to lower-than-expected efficacy microbicides. Our objective was study immune microenvironment cervix and uterus. In this randomized crossover study, 27 healthy volunteers used nightly application nonoxynol-9 (N9) gel as “failed” microbicide or universal placebo (UPG) “safe” (intervention cycles), nothing (control cycle) end menses mid-luteal phase. At specific time-point following ovulation, all participants underwent sample collection measurements T-cell phenotypes, gene expression, cytokine/chemokine protein concentrations 3 anatomic sites above vagina: cervical transformation zone, endocervix endometrium. hierarchical statistical models estimate mean (95% CI) intervention effects, N9 UPG relative control. Exposure generated common “harm signal” included transcriptional up-regulation inflammatory genes chemokine (C-C motif) ligand 20 (macrophage factor-3alpha) interleukin 8 in cervix, decreased secretory leukocyte protease inhibitor, mediators glycodelin-A osteopontin These need be replicated larger sample, underscore consider agents excipients studies vaginal