Timing of menstrual cups to prevent transition from optimal to not optimal vaginal microbiome community state type: Results from a 6.5-year prospective observational cohort

Background: In a cluster randomized trial among Kenyan secondary schoolgirls, menstrual cups were associated with reduced bacterial vaginosis (BV) and increased optimal vaginal microbiome (VMB) community state type (CST-I) prevalence. The prevalence of CST-I decreased over time, suggesting non-optimal VMB is acquired. Using 6.5 years follow-up, we identified how menstrual cups and other factors drive CST transition. Methods: Participants were randomized to receive menstrual cups (intervention) or standard menstrual management (control). VMB and BV were measured 6-monthly and sexually transmitted infections (STIs; gonorrhea, chlamydia, trichomoniasis) and HSV-2 annually. Control participants received menstrual cups after the 30-month study visit. Continuous-time multi-state Markov modeling estimated the probability of CST transition, focusing on optimal CST-I ( L. crispatus dominant), CST-III ( L. iners dominant), and CST-IV (mixed, non-optimal), and identified associated factors. Findings: Over 6.5 years, in 4,446 observations among 436 participants, CST-I prevalence decreased from 43.3% at baseline to 13.9%, and CST-IV increased from 18.1% at baseline to 44.6%. CST-I and CST-IV were more stable than CST-III. The probability of transition to CST-I from CST-III (16%) or CST-IV (9%) was infrequent. Participants initially randomized to menstrual cups had 54% reduced risk of transitioning from CST-I to CST-IV, adjusted for demographic and behavioral practices, BV, STIs, and HSV-2. Those who were poorer, older, sexually active, and HSV-2 seropositive were more likely to transition to less optimal CSTs. Interpretation: Over 6.5 years of observation, menstrual cups helped maintain CST-I VMB but did not demonstrate any therapeutic effect and should therefore be given to girls prior to sexual exposure to maximize the likelihood of achieving this benefit.