The vaginal microbiota, symptoms, and local immune correlates in transmasculine individuals using sustained testosterone therapy

Transmasculine individuals (assigned female at birth, masculine gender identity, TM) may use gender-affirming testosterone therapy, and some report adverse genital symptoms during treatment. In cis women, the vaginal microbiota is central to reproductive and sexual health. Lactobacillus-dominant communities are considered optimal, while diverse, Lactobacillus-depleted microbiota are non-optimal. Prior studies suggest Lactobacillus deficiency in TM vaginal microbiota, but associations with symptoms and immune markers remain unclear. We launched the TransBiota study to characterize the TM vaginal microbiota, soluble mediators of local inflammation, and self-reported symptoms over three weeks. Fewer than 10% of TM possess Lactobacillus-dominant microbiota, and most exhibit diverse, Lactobacillus-depleted microbiota. We identify 11 vaginal microbiota community state types (tmCSTs), with Lactobacillus-dominant tmCSTs unexpectedly linked to abnormal odor and elevated interleukin-1α. However, Lactobacillus dominance is not associated with other key symptoms, such as dyspareunia and vaginal dryness, underscoring that microbiome-symptom relationships in TM are more complex and warrant further research.