Two new studies offer contrasting insights into the mental health impacts of gender-affirming medical care, highlighting the complexity of transgender healthcare outcomes. A large-scale analysis of medical records published in The Journal of Sexual Medicine found that transgender individuals who underwent gender-affirming surgery were more likely to be diagnosed with depression, anxiety, and other mental health conditions compared to those who did not have surgery. In contrast, a longitudinal study published in JAMA Network Open found that transgender and nonbinary adults who received gender-affirming hormone therapy were significantly less likely to report symptoms of moderate-to-severe depression over time.
The research was conducted to address ongoing questions about the mental health outcomes associated with gender-affirming care. Transgender individuals—those whose gender identity does not align with the sex assigned at birth—often face a heightened risk of psychological distress. These difficulties can stem from factors such as societal stigma, discrimination, and the internal conflict of gender dysphoria.
Many seek gender-affirming treatments, including hormone therapy and surgical procedures, to alleviate this distress. While earlier studies have indicated psychological benefits from these interventions, the long-term mental health impact of surgery remains unclear, especially due to the limitations of small sample sizes and reliance on self-reported data.
The first study: Gender-affirming surgery linked to higher post-surgical mental health risks
To improve upon previous research, the authors of the study published in The Journal of Sexual Medicine used a large-scale dataset drawn from the TriNetX database, which compiles de-identified electronic medical records from more than 64 healthcare organizations in the United States. The analysis focused on patients aged 18 and older who had been diagnosed with gender dysphoria, using diagnostic codes from the International Classification of Diseases.
Among more than 107,000 individuals identified with gender dysphoria between 2014 and 2024, researchers formed several matched cohorts, comparing patients who had undergone gender-affirming surgery to those who had not. To ensure more accurate comparisons, they matched participants on age, race, and ethnicity using a statistical technique called propensity score matching.
Mental health outcomes were measured using clinical diagnoses documented in the medical records, rather than relying on self-reported surveys. Researchers focused on several conditions commonly observed in transgender populations: depression, anxiety, suicidal ideation, substance use disorder, and body dysmorphic disorder. They then examined how frequently these diagnoses appeared in patients’ records following surgery and compared the results across gender groups.
The findings revealed consistent patterns. Among individuals recorded as male in the medical records and diagnosed with gender dysphoria, those who had surgery had more than double the rate of depression compared to those who had not (25.4% vs. 11.5%) and nearly five times the rate of anxiety (12.8% vs. 2.6%). Suicidal ideation and substance use disorders were also more common in the surgical group. A similar trend appeared among patients recorded as female: those who underwent surgery were more likely to be diagnosed with depression (22.9% vs. 14.6%), anxiety (10.5% vs. 7.1%), suicidal ideation (19.8% vs. 8.4%), and substance use disorders (19.3% vs. 7.1%).
To explore whether these risks differed by type of gender transition, the researchers also examined individuals who had undergone masculinizing or feminizing surgeries but did not have a documented diagnosis of gender dysphoria. Even in this broader group, transgender men faced higher rates of mental health diagnoses compared to transgender women. For instance, the relative risk of depression was nearly 80% higher for transgender men. Rates of anxiety and substance use were also elevated.
Interestingly, across all comparisons, rates of body dysmorphic disorder—a condition involving distress over perceived flaws in physical appearance—did not differ between surgical and non-surgical groups. This suggests that dissatisfaction with surgical outcomes or body image was not the primary driver of the mental health disparities observed.
The study’s authors stress that the results should not be interpreted to mean that gender-affirming surgery causes poor mental health. Instead, they suggest that the observed associations may reflect a complex mix of social, emotional, and medical factors that persist even after surgery. Transgender individuals who choose to pursue surgery may already be experiencing greater psychological distress. At the same time, the stress of undergoing a major medical procedure, coupled with ongoing experiences of social stigma and limited access to mental health resources, may contribute to the emergence or worsening of mental health conditions.
One possible explanation raised by the authors involves the way psychiatric diagnoses are assigned. Before surgery, symptoms of depression or anxiety may be interpreted by clinicians as part of the gender dysphoria diagnosis. After surgery, however, these symptoms may be identified as independent conditions, leading to an apparent increase in diagnoses. This shift in diagnostic framing could influence how mental health outcomes are recorded and understood.
The second study: Gender-affirming hormone therapy linked to lower depression rates
On the other hand, the study published in JAMA Network Open found evidence that gender-affirming hormone therapy is associated with lower rates of moderate-to-severe depressive symptoms among transgender, nonbinary, and gender-diverse adults receiving care in community health centers. Over a four-year period, patients who were prescribed gender-affirming hormones experienced a 15% lower risk of clinically significant depression symptoms compared to those not receiving hormone therapy.
The research was part of the LEGACY project, a longitudinal study conducted at two federally qualified community health centers with extensive experience in providing care to transgender and nonbinary patients—Fenway Health in Boston and Callen-Lorde in New York City. The study followed 3,592 adult patients who had visited these clinics between 2016 and 2019. All participants were at least 18 years old, had a gender identity different from the sex assigned at birth, and had completed at least two depression screenings using a standardized questionnaire.
The researchers assessed depression symptoms using versions of the Patient Health Questionnaire, a widely used mental health screening tool. Moderate-to-severe depression was defined by standard clinical cutoffs. Patients were classified based on whether they had been prescribed hormone therapy during each year of follow-up. The researchers also collected extensive background information, including participants’ age, race and ethnicity, gender identity, income level, insurance status, HIV status, and other relevant health and demographic characteristics.
Overall, the sample was diverse. The median age was 28, and nearly one in five participants identified as nonbinary. Just over half lived below the federal poverty line. About 12% were Black, 16% were Hispanic, and 5% were living with HIV. At the start of the study, 84.5% of participants were already prescribed gender-affirming hormone therapy. At that same time, 15.3% of participants met criteria for moderate-to-severe depression.
Using statistical models that accounted for demographic differences and potential confounding factors, the researchers found that patients who received hormone therapy had a lower risk of experiencing moderate-to-severe depression symptoms over time. The adjusted risk ratio was 0.85, meaning there was a 15% reduction in the likelihood of clinically significant depression symptoms for those on hormone therapy compared to those who were not.
The study also identified other factors that were associated with a higher risk of depression. Younger participants, transgender women, nonbinary individuals assigned female at birth, those with public insurance, and individuals living in poverty were more likely to report depression symptoms. Patients who were HIV-negative but prescribed pre-exposure prophylaxis (PrEP) also had elevated rates of depression, possibly reflecting greater awareness of or anxiety about HIV risk. In contrast, Asian and Black participants, as well as older adults and patients from the New York clinic, had lower rates of depression symptoms.
What might explain the different outcomes observed?
The contrasting outcomes between the two studies may be explained by differences in study design, timing, and clinical context. The surgery study used cross-sectional data and clinical diagnoses, likely capturing patients during a stressful post-operative period when mental health issues are more likely to surface or be formally diagnosed. In contrast, the hormone therapy study used longitudinal, self-reported data and tracked patients over time, revealing gradual improvements in depression symptoms.
Other factors, such as differences in patient populations, levels of healthcare access, the role of social support, and the biological effects of hormones, may also contribute to the observed patterns. Diagnostic practices may shift after surgery, leading to more recorded mental health conditions that do not necessarily reflect worsening well-being.
As with all research, both studies have limitations to consider.
Although the study published in The Journal of Sexual Medicine used clinical data, which enhances its reliability, the data were collected from a broad network of health systems, which may introduce inconsistencies in how diagnoses are recorded. There are also concerns about misclassification. For example, individuals categorized as not having surgery may have had procedures done outside the database’s network. And because the study excluded patients with any prior mental health diagnosis, some pre-existing conditions may have been missed if they were never formally documented. In addition, because the study was cross-sectional, it could not track individual patients over time or establish causality.
The JAMA Network Open study, in contrast, used longitudinal data, allowing the researchers to better assess the direction of the relationship. However, the data were still observational, meaning they cannot prove that gender-affirming hormone therapy directly causes improvements in depression symptoms. Because participants were not randomly assigned to receive or not receive hormone therapy, other factors might have influenced the results. For example, patients who sought out hormone therapy may have had greater access to healthcare, more social support, or better mental health to begin with—factors that could independently contribute to lower rates of depression. The study also did not assess how long participants had been on hormone therapy or whether they underwent gender-affirming surgeries, both of which could influence mental health outcomes.
The study, “Examining gender-specific mental health risks after gender-affirming surgery: a national database study,” was authored by Joshua E. Lewis, Amani R. Patterson, Maame A. Effirim, Manav M. Patel, Shawn E. Lim, Victoria A. Cuello, Marc H. Phan, and Wei-Chen Lee.
The study, “Gender-Affirming Hormone Therapy and Depressive Symptoms Among Transgender Adults,” was authored by Sari L. Reisner, David R. Pletta, Alex S. Keuroghlian, Kenneth H. Mayer, Madeline B. Deutsch, Jennifer Potter, Jaclyn M. W. Hughto, Alexander Harris, and Asa E. Radix
