Contraceptive rings promote vaginal lactobacilli in a high bacterial vaginosis prevalence population: A randomised, open-label longitudinal study in Rwandan women

Abstract

BackgroundHormonal contraception has been associated with a reduced risk of vaginal dysbiosis, which in turn has been associated with reduced prevalence of sexually transmitted infections (STIs), including HIV. Vaginal rings are used or developed as delivery systems for contraceptive hormones and antimicrobial drugs for STI and HIV prevention or treatment. We hypothesized that a contraceptive vaginal ring (CVR) containing oestrogen enhances a lactobacilli-dominated vaginal microbial community despite biomass accumulation on the CVR’s surface.MethodsWe enrolled 120 women for 12 weeks in an open-label NuvaRing® study at Rinda Ubuzima, Kigali, Rwanda. Vaginal and ring microbiota were assessed at baseline and each ring removal visit by Gram stain Nugent scoring (vaginal only), quantitative PCR for Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae, and fluorescent in situ hybridization to visualize cell-adherent bacteria. Ring biomass was measured by crystal violet staining.ResultsBacterial vaginosis (BV) prevalence was 48% at baseline. The mean Nugent score decreased significantly with ring use. The presence and mean log10 concentrations of Lactobacillus species in vaginal secretions increased significantly whereas those of G. vaginalis and presence of A. vaginae decreased significantly. Biomass accumulated on the CVRs with a species composition mirroring the vaginal microbiota. This ring biomass composition and optical density after crystal violet staining did not change significantly over time.ConclusionsNuvaRing® promoted lactobacilli-dominated vaginal microbial communities in a population with high baseline BV prevalence despite the fact that biomass accumulated on the rings.

Daily Vaginal Microbiota Fluctuations Associated with Natural Hormonal Cycle, Contraceptives, Diet, and Exercise

“…Consistent with the present results, a recent meta-analysis supports the proposal that Lactobacillus growth in the vaginal environment is hormone-driven (31). While many reports have focused on how estrogens may promote Lactobacillus growth, less attention has been given to the possible role of progestins (32,38,(40)(41)(42)(43). The focus directed toward estrogens as promoters of Lactobacillus growth is based on epidemiologic observations of the major vaginal microbial changes that occur throughout the course of life.…”

“…In contrast, another study found no change in alpha diversity during menses, despite a decrease in stability (32). It is also unclear whether the menstrual changes indicate a relationship between vaginal microbiota and estrogen levels (31,32,38,(40)(41)(42)(43) or other factors such as progesterone levels (44) or the presence of menstrual blood (16). Whether diet, exercise, or even mood interact with vaginal microbiota is less understood, even though the influences of these host factors have been studied extensively in other microbial systems, including the gut microbiome (45)(46)(47).…”

“…Therefore, it is important to understand the host-microbiome interactions that regulate the vaginal microbiota and drive such individualization. Several host factors that influence the vaginal microbiota have been identified, including menses (31)(32)(33)(34)(35)(36)(37), intercourse (38,39), and hormonal contraceptive use (38,(40)(41)(42). However, the exact nature and mechanism of how these components regulate vaginal microbiota remain unknown.…”

Diversity of vaginal microbiota in sub-Saharan Africa and its effects on HIV transmission and prevention

“…66,67 Use of contraceptive vaginal rings containing estrogen has also been shown to significantly lower concentrations of BV-associated bacteria G vaginalis and A vaginae while promoting lactobacilli colonization. 68 On the other hand, consistent condom use increases the abundance of L crispatus within the vaginal tract and a healthy Nugent score of 0e3 is more common in condom users than women who use intrauterine device for contraception. 66 Sexual practices Sexual intercourse and the use of lubricants are associated with rapid changes in vaginal microbiota and a higher incidence of BV.…”

Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics

“…Combined oral contraceptives were shown to be associated with increased vaginal colonization by healthy lactobacilli, and with reduced bacterial vaginosis-associated taxa in another study (Brooks et al, 2017). Contraceptive rings were found to decrease the severity of bacterial vaginosis in African women by promoting the growth of vaginal lactobacilli and decreasing the abundance of Gardnerella vaginalis and Atopobium vaginae (Crucitti et al, 2018).…”