What is the optimal testosterone level for a female on hormone replacement therapy (HRT)?

Optimal Testosterone Levels for Females on HRT

For transgender men/transmasculine individuals on gender-affirming hormone therapy, target testosterone levels should be in the typical physiological range for cisgender men: 300-1,000 ng/dL, with most clinicians aiming for mid-normal range (450-600 ng/dL) to optimize virilization while minimizing adverse effects. 1, 2

Target Testosterone Range

• The recommended target is 300-1,000 ng/dL, which represents the normal physiological range for cisgender males 1
• Many experienced clinicians aim for the mid- to upper-normal range (450-600 ng/dL) to optimize therapeutic response while maintaining safety 2
• This range promotes expected masculinizing effects including voice deepening, increased muscle mass and strength, body composition changes, and increased libido 1, 3

Monitoring Protocol

Initial Phase

• Measure testosterone levels 2-3 months after treatment initiation or after any dose adjustment 2, 4
• For injectable testosterone, measure levels midway between injections, targeting mid-normal values (500-600 ng/dL) 2
• For transdermal preparations, levels can be measured at any time, though peak values occur 6-8 hours after application 2

Maintenance Phase

• Once stable levels are achieved on a given dose, monitor every 6-12 months 2, 4
• Continue monitoring hematocrit/hemoglobin, lipid profiles, and blood pressure due to testosterone's effects on these parameters 1

Dose-Response Considerations

• Early masculinizing effects (within 1 month) are dose-dependent, with higher doses producing faster onset of voice deepening, facial hair growth, and menstrual cessation 3
• However, by 6 months, most patients achieve therapeutic effects regardless of dose within the therapeutic range, suggesting no need for supraphysiological dosing 3
• Use the minimal dosing necessary to achieve target levels of 450-600 ng/dL 2

Safety Considerations and Monitoring

Cardiovascular Risk

• Testosterone may increase blood pressure, triglycerides, and LDL cholesterol while decreasing HDL 1
• Despite these metabolic changes, current data show little to no significant impact on cardiovascular mortality outcomes in transgender men 1
• This contrasts with transgender women, who show increased cardiovascular risk with hormone therapy 1

Hematologic Monitoring

• Erythrocytosis risk increases with testosterone therapy, particularly with injectable formulations 1, 4
• Monitor hematocrit at baseline and during follow-up visits 1
• To reduce erythrocytosis risk: advise smoking cessation, weight loss if BMI is elevated, and consider switching to transdermal administration 1

Bone Health

• Trans men undergoing gender-affirming treatment should be aware of risk to bone health associated with hypogonadism 1
• Adequate testosterone levels are protective, but inadequate dosing may negatively impact bone density 1

Common Pitfalls to Avoid

• Self-prescribed hormone therapy is often ineffective at achieving target testosterone levels, with one study showing only 25-48% of self-prescribing transgender women achieved appropriate hormone ranges 5
• Avoid supraphysiological dosing (>1,000 ng/dL), as this increases adverse effects without additional therapeutic benefit 2
• Do not use alkylated oral testosterone due to potential liver toxicity 2
• Ensure patients understand that testosterone therapy interrupts normal fertility and should not be used by those actively trying to conceive 2

Formulation Selection Impact

• Injectable testosterone (enanthate, cypionate) may cause greater fluctuations in levels, with peaks potentially reaching supraphysiological ranges 4
• Transdermal preparations (gels, patches) provide more stable day-to-day testosterone levels and may have lower risk of erythrocytosis 4
• Weekly injectable dosing (50-100 mg) provides more stable levels than biweekly dosing (100-200 mg) 4