Abstract

Introduction Hormonal contraception (HC) has been associated with a reduced risk of bacterial vaginosis (BV). We conducted a prospective study to evaluate the relationship between vaginal microbiota and several HC methods. Methods During 2-years of follow-up, 108 women provided 2,662 mid-vaginal samples. Participants reported three HC methods [oral contraceptive pill (OCP), vaginal ring, implanon]. Controls not taking HC were also followed. Visits were scheduled at baseline, 2 weeks, 4 weeks, 3 months, 6 months, 12 months, 18 months, and 24 months. Additionally, participants self-collected mid-vaginal swabs twice-weekly in the two weeks before each visit. Vaginal microbiota composition was characterised on all samples by 16S rRNA gene analysis of the V3-V4 hypervariable regions. We identified four community state types (CSTs) which were dominated by Lactobacillus species. CST-IV-B was characterised by a low relative abundance of Lactobacillus spp. and higher proportions of BV-associated bacteria (Gardnerella and Atopobium). A multinomial model for dependence of proportions was used to evaluate the association between CST and HC. Jensen-Shannon distances between all pairs of samples were analysed to assess stability of the microbiota longitudinally. Results Women on OCPs had more stable bacterial communities than controls during the 2-year follow-up (p = 0.04). HC (overall) also tended toward greater stability (p = 0.10). The low- Lactobacillus CST-IV-B had an 83% lower probability among OCP users and a 55% lower probability among implanon users. CST-II (L. gasseri-dominated) was significantly higher in all HC types compared to controls. Additionally, OCP users were more likely to be CST-III-A ( L. iners -dominated) and CST-V (L. jensenni-dominated), while CST-III-A was also high among ring users. CST-I (L. crispatus-dominated) was associated with implanon. All reported findings were statistically significant (p Conclusion Women on HC experienced greater stability of the vaginal microbiota over time compared to controls. OCPs and the vaginal ring were protective against transition to a Lactobacillus -depleted state. Disclosure of interest statement The study was funded by the US National Institute of Allergy and Infectious Diseases (NIAID) R01-AI089878. No pharmaceutical grants were received in the development of this study.

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