UID:
edocfu_9961535570502883
Format:
1 online resource (46 pages) :
,
illustrations.
Series Statement:
Final research report
Content:
BACKGROUND: Many transgender people undergo gender-affirming hormone therapy (HT) to align their physical appearance with their identity. A central part of gender-affirming HT in transfeminine (TF) people is estrogen, which is often taken in combination with testosterone-lowering medications. OBJECTIVES: The Study of Transition, Outcomes & Gender (STRONG) was initiated to assess morbidity among transgender people enrolled in Kaiser Permanente (KP) health plans in Georgia and northern and southern California. Findings from one of the primary analyses of the STRONG data indicated higher rates of venous thromboembolism (VTE) and ischemic stroke (IS) among TF participants receiving HT than the corresponding rates among cisgender men and women; however, the small numbers of events precluded comparisons of risks by different HT combinations, routes of administration, and doses. The overall goal of the current project was to characterize risk of VTE and IS in different subgroups of TF participants using data from the expanded STRONG cohort. METHODS: Electronic health records (EHRs) were used to identify and validate a cohort of 3325 TF members of KP who initiated HT from January 1, 2006, to January 1, 2020. Ten cisgender male and 10 cisgender female KP enrollees were matched to each transgender cohort member on year of birth, race/ethnicity, study site, and membership year of the index date (first evidence of transgender status in the EHR). Incidences of VTE and IS among TF participants were ascertained from diagnostic codes and compared with those in the reference cohorts using Cox regression models, with results expressed as hazard ratios (HRs) and 95% CIs. Subgroup analyses investigated the associations by route of estrogen administration and by specific types of HT drugs. Cohort members taking oral estradiol (the most common active ingredient) were placed into 2 groups: those whose initial daily dose was ≤2 mg and those whose starting dose exceeded 2 mg per day. RESULTS: Rates of both VTE and IS were higher among TF persons than in either reference group. In a subgroup that started and remained on oral estrogen, the HR for VTE was 1.9 (95% CI, 1.0-3.5) compared with cisgender men and 2.5 (95% CI, 1.4-4.5) compared with cisgender women. In contrast, the corresponding HR estimates for VTE in persons who started and remained on parenteral estrogen were 1.0 (95% CI, 0.4-2.4) and 1.1 (95% CI, 0.4-2.6). In the analyses for IS, the largest HR estimates were observed among TF persons who remained on parenteral estrogen for the duration of follow-up, at 2.8 (95% CI, 1.4-5.6) and 4.1 (95% CI, 1.9-8.7) relative to cisgender men and women, respectively. This increase in IS risk was most pronounced among persons who received injectable estradiol. The risk of VTE was less elevated among TF participants receiving estrogen in combination with testosterone-suppressing medications when lowering of testosterone levels was achieved through the use of spironolactone than when using antiandrogen medications such as finasteride. Exploratory analyses suggested that the risk of VTE among persons who remained on oral estradiol throughout the follow-up may be dose dependent. There was a paradoxical inverse relationship between the initial dose of oral estradiol and IS risk. CONCLUSIONS: These results suggest that that risk of VTE is higher among TF persons receiving oral estrogens than in those using parenteral routes. The rates of IS, however, appeared to be somewhat higher among study participants who did not receive any oral estrogen during follow-up. If confirmed, these results should be taken into consideration during HT initiation and clinical follow-up of TF patients. The findings of this report are likely to be considered in the next versions of the Standards of Care by the World Professional Association for Transgender Health and the Clinical Practice Guidelines by the Endocrine Society. LIMITATIONS: An important limitation of STRONG is the lack of data on hormone levels, which may be the best indicator of HT initiation and adherence. We also acknowledge that transgender people enrolled through integrated health care systems comprise a cohort that may not be representative of the entire transgender population in the United States.
Language:
English
DOI:
10.25302/05.2021.AD.SS4532
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