Management of Worsening Depression in a Transgender Man on Testosterone Therapy
Do not discontinue testosterone therapy, as gender-affirming hormone therapy (GAHT) consistently improves mental health outcomes in transgender men, and stopping it would likely worsen both gender dysphoria and depression. 1, 2, 3
Understanding the Clinical Context
The relationship between testosterone therapy and depression in transgender men differs fundamentally from other populations:
Systematic reviews demonstrate that GAHT produces a 20% decrease in depression after 1 year of treatment in transgender men and women, with no evidence of adverse mental health outcomes from hormonal therapy. 1, 2, 3
Transgender men on testosterone show quality of life improvements of 5.5 points on a 10-point scale after 1 year, with 67% of transgender men receiving testosterone reporting significantly higher quality of life scores than those not on hormone therapy. 1, 3, 4
Discontinuing GAHT can significantly worsen gender dysphoria and mental health outcomes, which represents a far greater risk than any potential hormone-related mood effects. 2, 3
Immediate Assessment Priorities
Rule Out Non-Hormonal Causes First
Evaluate psychosocial stressors, medication adherence, and adequacy of psychiatric treatment rather than immediately attributing worsening depression to testosterone. 2
Key factors to assess:
Transgender individuals experience discrimination, lack of access to healthcare, and lack of provider comfort/knowledge, which are predictors of poor mental health outcomes. 1
Risk factors for worsening depression include low self-esteem, lack of interpersonal support, hostile experiences, and lack of access to appropriate hormone treatment. 1
Transgender individuals have increased baseline rates of anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, and schizophrenia compared to cisgender populations. 2, 3
Verify Testosterone Dosing and Levels
Measure morning total testosterone levels (8-10 AM) to ensure adequate dosing, as suboptimal testosterone levels may contribute to mood symptoms. 5
For injectable testosterone, measure levels midway between injections (days 5-7), targeting mid-normal values of 500-600 ng/dL. 5
Inadequate testosterone dosing in transgender men can perpetuate dysphoria and worsen mental health outcomes. 1, 2
Treatment Algorithm
Step 1: Optimize Psychiatric Management While Continuing Testosterone
Initiate or intensify antidepressant therapy while maintaining testosterone at therapeutic levels. 6, 7
Men with testosterone deficiency who are already on SSRIs experience significant improvement in depressive symptoms after initiating testosterone replacement therapy, suggesting additive benefits. 6
Testosterone acts as a modulator of GABAA receptors and inhibits 5-HT3 receptors centrally, providing a distinct mechanism from traditional antidepressants. 6
Consider a trial of at least 3 months of combined therapy, as testosterone replacement therapy alone may improve clinical symptoms of depression in some patients. 6
Step 2: Address Modifiable Risk Factors
Screen for and treat comorbid conditions that independently worsen depression:
Evaluate for sleep disorders, thyroid dysfunction, anemia, and vitamin D deficiency. 5
Assess for metabolic syndrome and cardiovascular risk factors. 5
If obesity is present, encourage weight loss through low-calorie diets and regular physical activity, which can improve both metabolic health and mood. 1, 5
Step 3: Monitor for Testosterone-Related Complications
While continuing testosterone, monitor for potential adverse effects that could indirectly affect mood:
Check hematocrit periodically and withhold treatment if >54%, as polycythemia can cause fatigue and mood changes. 1, 5
Screen for liver abnormalities before and during high-dose androgen therapy, as hepatic dysfunction can affect overall wellbeing. 1
Monitor for fluid retention and other physical side effects that may impact quality of life. 5
Evidence-Specific Considerations for Transgender Men
Recent research shows nuanced patterns in depressive symptoms with GAHT:
Transgender men report improvement in lethargy symptoms after 3 months of testosterone therapy (-16%), though absolute score changes are modest. 8
Unlike transgender women (who may experience slight increases in low mood with estrogen), transgender men do not show worsening of mood symptoms with testosterone. 8
Neither anxiety nor somatic symptoms worsen with testosterone therapy in transgender men. 8
Critical Pitfalls to Avoid
Never discontinue testosterone based solely on worsening depression without thoroughly investigating other causes, as this will likely worsen both gender dysphoria and overall mental health. 2, 3
Do not assume the testosterone is causing the depression—the evidence strongly suggests the opposite, with hormone therapy being protective for mental health in transgender individuals. 1, 2, 3
Recognize that up to 35% of transgender individuals would continue hormone therapy even if diagnosed with a hormonally dependent cancer, reflecting the profound importance of GAHT for mental health and quality of life. 3
Avoid attributing all mood changes to hormones when psychosocial stressors, discrimination, and lack of social support are major contributors to depression in transgender populations. 1, 2
Expected Outcomes with Appropriate Management
With continued testosterone therapy and optimized psychiatric treatment:
Mental health improvements typically manifest within 3-6 months of adequate testosterone dosing. 1, 4
Quality of life scores improve significantly, particularly in domains related to body satisfaction, gender dysphoria, and overall wellbeing. 1, 4
The combination of testosterone therapy and appropriate antidepressant treatment provides additive benefits for mood symptoms. 6, 7