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 TM report adverse genital symptoms during treatment. In cis women, the vaginal microbiota is a key determinant of reproductive and sexual health outcomes; Lactobacillus -dominant communities are considered optimal, while more even, diverse, Lactobacillus -depleted microbiota are considered 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 (SMI), and self-reported symptoms over three weeks. Fewer than 10% of TM possessed Lactobacillus -dominant microbiota, and most exhibited more diverse, Lactobacillus- depleted microbiota. We identified 11 vaginal microbiota community state types (tmCSTs), with Lactobacillus -dominant tmCSTs unexpectedly linked to abnormal odor and elevated IL-1α. These findings indicate that Lactobacillus dominance may no longer be an optimal state for TM during gender-affirming testosterone therapy and change in clinical management is needed.