Abstract

<h3>Background</h3> Uterine bleeding (UB) on testosterone is an emerging problem in trans masculine (TM, sex assigned female at birth who identify on the masculine spectrum) health. While most TM individuals achieve amenorrhea within a year of testosterone initiation, not all do. Little data exists on the frequency of UB following amenorrhea induction, and no guidelines exist to provide a clinical approach. The study goal was to characterize UB patterns and associated risk factors in TM adolescents on testosterone for greater than a year, and describe the diagnostic and management approaches. <h3>Methods</h3> This was an IRB approved retrospective cohort study of all TM patients seen for gender affirming testosterone therapy between 2010 and 2020. Inclusion criteria were testosterone use more than 1 year, Mullerian anatomy, and documentation of the presence or absence of UB. Variables included demographics, characteristics of testosterone therapy, serum sex steroid levels, and use of non-androgen hormones. Primary outcome was the presence of UB after 1 year on testosterone. <h3>Results</h3> Of the 232 patients who met inclusion criteria, 25% (n=58) had at least 1 episode of UB after 1 year on testosterone. No significant differences between the UB and non-UB groups were found for mean age of testosterone initiation (16.3+/-2.2 vs 16.3+/-1.8 years, p=0.86) or BMI (p=0.33). The mean duration of testosterone use was significantly longer in the UB group (37.3+/-17.0 vs 28.5+/-14.6 months, p=<0.001). There was no difference in the use of non-androgen hormones between the UB (n=31, 53.4%) and non-UB groups (n=89, 51.1%), but those who used gonadotropin releasing hormone analogs (GnRHa) were 5.8 times more likely to be in the non-UB group (95% CI 0.7-44.5, p=0.07). Testosterone and estradiol levels (taken near the bleeding episode(s)) in the UB group were not statistically different than the latest levels from the non-UB group (p=.46 and p=.052 respectively). Only 3 UB patients had imaging and 1 had thyroid testing. UB causes were idiopathic/other (40), low/missed doses (13), and changes in non-androgen hormone use (5). UB management included testosterone dose adjustment (14), progestin initiation (13), or GnRHa (2). Eight patients underwent hysterectomy for both UB and gender affirmation after testosterone use, mean duration 41.8+/-20.6 months. <h3>Conclusions</h3> This is the first long term study to describe UB patterns in TM patients. GnRHa users had the highest odds of inducing or maintaining amenorrhea following new onset UB. All menstrual suppression options should be offered, as no other method was felt to be superior for addressing new onset UB. Future studies will be needed to better stratify the success of various UB management.

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