The Oral Contraceptive Pill Favorably Influences the Vaginal Microbiota but Sexual Activity Drives BV Recurrence
Vodstrcil LA1,2, Ratten, LK1, Plummer EL1, Fairley CK1, Murray G3, Garland SM3, Tachedjian G4, Law M5, Hocking JS2, Danielewski J3, Chow EPF1, Bradshaw CS1,2
1Central Clinical School, Monash University & Melbourne Sexual Health Centre, Alfred Health; 2School of Population & Global Health, University of Melbourne; 3Royal Women's Hospital; 4Burnet Institute; 5Kirby Institute, UNSW Australia
We conducted an open-label RCT of oral contraceptive pill (OCP)-use to determine if it reduced BV recurrence. Women with BV were prescribed first-line antibiotics, randomized to OCP or current non-hormonal contraception, and returned vaginal swabs and questionnaires monthly for 6mo or until BV-recurrence. Modified intention-to-treat methods were used to determine cumulative recurrence rates. Cox regression analyses, adjusted for randomization, assessed factors associated with recurrence in all women. Specimens (N=449) underwent vaginal microbiota (VM) analysis by 16s rRNA V3V4 gene sequencing. Recurrence rates did not differ in women randomized to the OCP (10/100PY,95%CI:6,19) compared to controls (14/100PY,95%CI:9,21). However, increased risk of recurrence was associated with sex with an ongoing regular sexual partner (RSP;AHR=3.09,95%CI:1.40,6.87). Baseline pre-treatment specimens had a Gardnerella vaginalis dominant or highly diverse VM, while post-treatment specimens had a low diversity Lactobacillus dominated VM. OCP-exposure was associated with lower VM diversity (adj Shannon co-eff=-0.55,95%CI:-0.75,-0.36). Women with OCP-exposure were more likely than women without OCP-exposure to have a VM dominated by L. crispatus (RRR=3.12,95%CI:1.24,7.81) or L. iners (RRR=4.40,95%CI:1.90,10.18) than G. vaginalis. Exposure to an RSP was associated with increased diversity (adj Shannon co-eff=0.26, 95%CI:0.034,0.48) and a higher abundance of G. vaginalis (AOR=1.86,95%CI:1.07,3.23). While this RCT of OCP-use did not improve BV cure it did increase the likelihood of a Lactobacillus dominant VM. Importantly, RSP exposure increased the likelihood of a highly diverse or G. vaginalis dominant microbiota, highlighting the contribution of reinfection to post-treatment recurrence. These data have important implications for the development of BV treatment and prevention strategies.
Funds: Monash University (CB); Early Career Research Grant, University of Melbourne (LV)