Persistent vaginal bleeding during gender-affirming hormone therapy in transgender men.

Breakthrough bleeding in transgender men on testosterone therapy was associated with decreased testosterone levels compared with controls.

• Case-control study with 24 transgender men in the case group (breakthrough bleeding) and 48 in the control group
• All participants had been on gender-affirming hormone therapy (GAHT) for at least 6 months
• Testosterone levels were significantly lower in the case group compared to controls (p = 0.002)
• Univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028)

Breakthrough bleeding was associated with decreased free androgen index (FAI) compared with controls.

• FAI was significantly lower in transgender men with breakthrough bleeding compared to controls (p = 0.008)
• Univariate prevalence ratio analysis showed a negative association of persistent bleeding with FAI levels (p = 0.019)

Transgender men with breakthrough bleeding were disproportionately represented in the lowest testosterone tertile.

• 50% of individuals with breakthrough bleeding had testosterone levels below the lowest tertile calculated for the sample
• Only 18.8% of controls had testosterone levels below the lowest tertile
• This difference was statistically significant (p = 0.007)

Adjustment of testosterone therapy resulted in increased testosterone levels following the initial breakthrough bleeding episode.

• After therapy adjustment, testosterone levels increased compared with the values obtained at the initial bleeding episode (p = 0.031)

A subset of transgender men with breakthrough bleeding required addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI.

• 8 transgender men required the addition of an oral progestogen to achieve amenorrhea
• These individuals had significantly higher BMI than those in whom adjustment of the parenteral testosterone dose alone was adequate (p = 0.026)
• Higher BMI was identified as one of the main factors associated with breakthrough bleeding

The study used a case-control design assessing multiple variable categories to identify factors associated with breakthrough bleeding.

• Variables assessed included clinical, sociodemographic, hormonal, and body composition variables
• Body composition was measured using dual-energy X-ray absorptiometry (DXA)
• 24 cases and 48 controls were included, with all participants having been on GAHT for at least 6 months