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Observational Study
. 2025 Mar 3;8(3):e250955.
doi: 10.1001/jamanetworkopen.2025.0955.

Gender-Affirming Hormone Therapy and Depressive Symptoms Among Transgender Adults

Sari L Reisner  1   2   3   4   5 , David R Pletta  1 , Alex S Keuroghlian  5   6 , Kenneth H Mayer  5   7 , Madeline B Deutsch  8 , Jennifer Potter  5   7 , Jaclyn M W Hughto  5   9   10   11 , Alexander Harris  12 , Asa E Radix  12   13
Affiliations
Observational Study

Gender-Affirming Hormone Therapy and Depressive Symptoms Among Transgender Adults

Sari L Reisner et al. JAMA Netw Open. .

Abstract

Importance: In the US, transgender, nonbinary, and gender diverse (TGD) adults have high rates of depression. Gender-affirming hormone therapy (GAHT) is associated with improved mental health outcomes, yet existing US studies have short follow ups and lack sample diversity.

Objective: To evaluate the use of GAHT delivered in primary care as an intervention for moderate-to-severe depressive symptoms in diverse TGD adult patients.

Design, setting, and participants: LEGACY was an observational cohort study conducted in federally qualified community health centers in Boston and New York that followed up TGD patients (N = 3592) from calendar years 2016 to 2019 (48 months). Participants included individuals aged 18 years or older, gender identity different from sex at birth, a past 12-month medical visit, and signed patient consent form in the electronic health record (EHR).

Exposures: Prescriptions for GAHT obtained from EHR data, using the date of the first and last GAHT prescription in each calendar year of observation (GAHT within the year vs no GAHT during the year).

Main outcomes and measures: A binary outcome of patient-reported moderate-to-severe depressive symptoms was obtained using the validated Patient-Health Questionnaire (PHQ), scoring 10 or greater on the PHQ-9 or scoring 3 or greater on the PHQ-2. Following multiple imputation, generalized estimating equations (GEE) longitudinally modeled GAHT and moderate-to-severe depressive symptoms (n = 20 320 observations) and adjusted for age, gender identity, race and ethnicity, health insurance, federal poverty level, HIV serostatus, number of cohort years, and clinical site.

Results: The median age of the 3592 patients was 28 (IQR, 24-36) years. Race and ethnicity was diverse (1.3% Asian/Pacific Islander, 11.7% Black, 16.1% Hispanic/Latinx, 63.1% White, 6.8% multiracial, and 1.4% other). In addition, 18.9% were nonbinary, 52.1% lived below the federal poverty level, 34.2% were publicly insured, 4.1% were uninsured, and 5.1% were living with HIV. At baseline, 84.5% of the individuals were prescribed GAHT and 15.3% reported moderate-to-severe depressive symptoms. Patients prescribed GAHT had a statistically significantly lower risk of moderate-to-severe depressive symptoms over follow-up compared with those not prescribed GAHT (adjusted risk ratio, 0.85; 95% CI, 0.75-0.98).

Conclusions and relevance: In this longitudinal observational cohort study, GAHT was associated with lower rates of moderate-to-severe depressive symptoms, highlighting the importance of gender-affirming primary care models for TGD patients.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Reisner reported receiving royalties from McGraw Hill for editing a textbook outside the submitted work. Dr Keuroghlian reported receiving a patent for editing with royalties paid from McGraw Hill for a textbook on transgender and gender diverse health care and a patent for editing with royalties paid from the American Psychiatric Association Publishing for a textbook on gender-affirming psychiatric care. No other disclosures were reported.

References

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