Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, United States of America.
PLoS One. 2012;7(10):e46901. doi: 10.1371/journal.pone.0046901. Epub 2012 Oct 8.
Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota.
Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays.
The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08).
Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels of antimicrobial (lactoferrin) and anti-inflammatory (IL-1ra) proteins. These findings indicate the need for additional safety studies of this candidate non-hormonal contraceptive.
ClinicalTrials.gov NCT00850837.
酸式凝胶是一种可使精子失活的酸缓冲产品，可能是一种有效的局部非激素避孕方法。本研究旨在评估阴道给药的安全性以及酸式凝胶对黏膜免疫介质、生殖分泌物的抗菌特性和阴道微生物群的影响。
36 名性禁欲的美国女性被随机分为两组，每天两次阴道应用酸式凝胶或羟乙基纤维素（HEC）安慰剂凝胶，连续 14 天。通过症状和盆腔检查评估安全性。通过定量分析细胞因子、趋化因子、生殖分泌物中的抗菌蛋白和抗菌活性，评估凝胶对黏膜免疫的影响，这些细胞因子、趋化因子、抗菌蛋白和抗菌活性是在筛查时、凝胶应用后 2 小时以及第 7、14 和 21 天通过宫颈阴道灌洗（CVL）收集的。在入组时和第 14 天，使用种特异性定量 PCR 检测方法对阴道微生物群进行特征描述。
酸式凝胶应用后 2 小时，阴道和宫颈 pH 值中位数显著降低，与 CVL 对大肠杆菌的杀菌活性增加相关。然而，与接受安慰剂的女性（11%）相比，接受酸式凝胶的女性中有 65%至少出现了一种局部不良事件（p=0.002）。虽然细胞因子或趋化因子没有增加，但与 HEC 安慰剂凝胶相比，酸式凝胶应用后 CVL 中乳铁蛋白和白细胞介素 1 受体拮抗剂（IL-1ra）的浓度显著降低，IL-1ra 是一种抗炎蛋白。两组中乳杆菌 crispatus 或乳杆菌 jensenii 均无显著变化，但酸式凝胶组中阴道加德纳菌减少（p=0.08）。
酸式凝胶可能增强黏膜防御，表现为生殖分泌物对大肠杆菌的杀菌活性增加，阴道加德纳菌定植减少。然而，酸式凝胶引起的刺激比安慰剂多，且抗菌（乳铁蛋白）和抗炎（IL-1ra）蛋白水平较低。这些发现表明需要进一步研究这种候选非激素避孕药的安全性。
ClinicalTrials.gov NCT00850837。
