Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation

Abstract

Background: A contraceptive vaginal ring (CVR) containing Nestorone® (NES) and ethinyl estradiol (EE) that is reusable for 1- year (13 cycles) is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora.

Methods: There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology sub-study for up to 1- year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits). Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs), Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study.

Results: Over 1- year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H2O2-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7% at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 107 colony forming units (cfu) per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (104 to 103cfu per gram). There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed.

Conclusion: Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem.

Trial registration: ClinicalTrials.gov NCT00263341, NCT00455156.

Fig 1. Subjects’ disposition chart in microbiology study.

* Thirteen cases of abnormal pap smear, one current PID, one vaginal cyst, three migraines or headaches, one heavy smoking, one drug abuse, two hypertension, one abnormal blood cholesterol, one abnormal urine test. ** One in another study, one employed in the office. ^&Visit timing: Cycle 6 (targeted at Day 144 [beginning of Cycle 6], range 2 to 251); Cycle 13 (targeted at Day 358 [12 cycles plus 21 days of use during cycle 13], range 252 to 358).

Fig 2. Prevalence of selected vaginal microbiota by assessment window.

Visit timing: Cycle 6 (targeted at Day 144 [beginning of Cycle 6], range 2 to 251); Cycle 13 (targeted at Day 358 [12 cycles plus 21 days of use during cycle 13], range 252 to 358).

Fig 3. Prevalence and cumulative incidence rates of vaginal infections and urogenital infections in women in the substudy and remainder of women in Phase III trial.