What is the recommended treatment plan for a 40‑year‑old female‑to‑male transgender patient with bipolar disorder, including gender‑affirming testosterone therapy and appropriate mood‑stabilizing medication?

Treatment Plan for 40-Year-Old FTM Transgender Patient with Bipolar Disorder

Recommended Medication Regimen

For this patient, initiate testosterone therapy targeting serum levels of 300-1,000 ng/dL using intramuscular testosterone cypionate or enanthate (most cost-effective and equally effective as transdermal formulations), combined with a mood stabilizer for bipolar disorder—preferably avoiding valproate due to its association with elevated testosterone levels in females. 1, 2

Testosterone Therapy Protocol

Initiate testosterone cypionate or enanthate 250 mg intramuscularly every 2 weeks, as this regimen produces desired masculinizing effects promptly and effectively in transgender men. 3, 2

• Target trough testosterone levels between 300-1,000 ng/dL, preferably mid-normal range to optimize safety and efficacy. 1, 2
• Injectable testosterone esters can be administered subcutaneously for patient comfort if preferred. 1
• Avoid testosterone undecanoate due to concerns for pulmonary oil microembolism and anaphylaxis. 1, 2

Expected physical changes include:

• Voice deepening and cessation of menses within 3 months (87.1% and 78.8% respectively). 3
• Facial hair growth (52.9%), body hair growth (37.6%), and acne (69.4%) within 3 months. 3
• Increased muscle mass, strength, and libido. 1, 2, 3

Mood Stabilizer Selection for Bipolar Disorder

Avoid valproate as the primary mood stabilizer in this patient. 4, 5

• Valproate use is significantly associated with elevated total testosterone levels in female patients with bipolar disorder. 4
• In one study, valproate was the only significant predictor of testosterone levels when controlling for age and diagnosis. 4
• Women with bipolar disorder on valproate showed increased total testosterone over time compared to those on other mood stabilizers. 5

Consider lithium or atypical antipsychotics as alternative mood stabilizers, as these were not associated with testosterone elevation in bipolar disorder patients. 5

• Aripiprazole (Abilify) is commonly used for bipolar disorder and has no documented interactions with testosterone therapy. 6
• Monitor for changes in mood, anxiety, and psychiatric symptoms when combining testosterone with any psychiatric medication. 6

Critical Monitoring Parameters

Baseline Assessment (Before Starting Testosterone)

Obtain the following baseline labs: 6, 2

• Complete blood count (hemoglobin/hematocrit for erythrocytosis monitoring)
• Liver function tests
• Lipid profile (total cholesterol, LDL, HDL, triglycerides)
• Fasting glucose or HbA1c
• Baseline testosterone levels
• Blood pressure measurement

Ongoing Monitoring Schedule

Monitor at 3 months, then every 3-6 months during the first year, then annually if stable: 6, 2

Hematological Monitoring

• Hemoglobin will increase to male reference range within 3 months of starting therapy. 2
• Testosterone can cause erythrocytosis, particularly with injectable formulations. 1, 6, 2
• If hematocrit rises above normal male reference range, temporarily withhold therapy, reduce dose, or perform phlebotomy. 2
• Consider switching to transdermal testosterone if erythrocytosis develops. 1, 6

Cardiovascular Monitoring

• Monitor blood pressure regularly, as testosterone may increase blood pressure. 1, 6, 2
• Check lipid profiles, as testosterone may increase triglycerides and LDL cholesterol while decreasing HDL. 1, 6, 2
• Despite these risk factor changes, studies show contradictory data with no significant difference in cardiovascular mortality in transgender men compared to the general population. 1, 6

Hormone Level Monitoring

• Check trough testosterone levels (drawn just before next injection) to ensure levels are 300-1,000 ng/dL. 2
• Adjust dosing to maintain mid-normal range. 2

Laboratory Value Interpretation After 12 Months

After 12 months on testosterone therapy, interpret laboratory values using male reference ranges: 6

• Use male reference ranges for hemoglobin, creatinine, and liver enzymes. 6
• Cystatin C may be preferred over creatinine for kidney function evaluation, as it is less dependent on muscle mass. 6

Risk Reduction Strategies

To reduce risks associated with erythrocytosis: 1, 6

• Advise smoking cessation
• Recommend weight loss if BMI is elevated
• Consider switching to transdermal testosterone if erythrocytosis develops

Special Considerations for Bipolar Disorder

Be aware that testosterone levels may influence mood and suicidal behavior in individuals with bipolar disorder: 7, 8

• Women with bipolar disorder have significantly higher baseline testosterone levels than female controls. 7
• Higher baseline testosterone levels predicted suicide attempts during follow-up in females with bipolar disorder. 8
• Testosterone levels positively correlated with number of previous major depressive episodes and suicide attempts. 8

However, gender-affirming testosterone therapy is medically necessary and shows strong evidence of improving quality of life and relieving psychological distress associated with gender dysphoria. 2

• Monitor closely for mood changes, emotional instability (reported in 9.4% of transgender men), and changes in libido (7.1%). 3
• Maintain regular psychiatric follow-up to assess bipolar symptom control. 6

Fertility Counseling

Discuss fertility preservation options before initiating testosterone therapy: 1

• Oocyte banking is available if desired for future biological children. 1
• Reproduction can be safe and successful after testosterone therapy, though data are limited. 1
• Some transgender men have achieved successful oocyte retrieval while on testosterone. 1

Bone Health Considerations

Ensure adequate testosterone dosing to protect bone health: 1, 2

• Transgender men undergoing gender-affirming treatment face risk to bone health associated with hypogonadism. 1
• Inadequate testosterone dosing can negatively impact bone density. 2

Cancer Screening

Continue recommended cancer screenings: 1

• Breast cancer screening is recommended for transgender men not electing chest surgery. 1
• Cervical cancer screening is recommended for those who have not had hysterectomy. 1
• Based on available data, there is no significant mortality difference between transgender men and the general population, and no data suggest a link between long-term testosterone therapy and cancer development. 1