Laboratory Assessments for Transgender Individuals on Hormone Replacement Therapy
Baseline Laboratory Assessment Before Initiating HRT
Before starting gender-affirming hormone therapy (GAHT), obtain a comprehensive baseline assessment including complete blood count, comprehensive metabolic panel (liver function tests, electrolytes, creatinine), lipid profile, glucose levels, and baseline hormone levels (testosterone, estradiol). 1
- Complete blood count establishes baseline hemoglobin and hematocrit, which will shift significantly with hormone therapy 1, 2
- Liver function tests (ALT, AST, alkaline phosphatase) provide baseline values as these enzymes shift toward the affirmed gender range 3
- Lipid panel is essential as testosterone increases triglycerides and LDL while decreasing HDL, and estrogen therapy alters lipid profiles 3, 2
- Baseline creatinine is critical for future renal function assessment, as this value changes with muscle mass alterations from GAHT 3
- Baseline hormone levels (testosterone and estradiol) guide dosing adjustments to achieve target ranges 1
Monitoring Schedule During HRT
Monitor hormone levels at 3 months after initiation, then every 3-6 months during the first year, transitioning to annual monitoring once hormone levels are stable. 1, 4
First Year Monitoring (Every 3-6 Months):
- Testosterone or estradiol levels to ensure therapeutic targets are achieved 1
- Complete blood count, particularly hemoglobin and hematocrit, as red blood cell indices stabilize within 6 months but require monitoring for polycythemia (in transgender men) or anemia (in transgender women) 5, 2, 6
- Liver function tests, as enzyme levels shift toward affirmed gender ranges 3, 2
- Lipid panel, especially in transgender men where triglycerides increase and HDL decreases beyond the first year 3, 6
- Creatinine and renal function assessment 3
After First Year (Annual Monitoring):
- Continue annual monitoring of all baseline parameters once stable 1, 4
- Hemoglobin and hematocrit to detect polycythemia in long-term testosterone users 5
Target Hormone Levels
For Transgender Women (Feminizing Therapy):
For Transgender Men (Masculinizing Therapy):
- Target testosterone 300-1,000 ng/dL (cisgender male reference range) 1
- Hemoglobin will increase to male reference range within 3 months 1
Laboratory Value Interpretation: The Critical 12-Month Rule
After 12 months of consistent GAHT, interpret laboratory values using the reference range for the affirmed gender; before 12 months, interpret values in the context of type, dose, and duration of therapy. 3, 1, 4
Values That Shift to Affirmed Gender (Use Affirmed Gender Reference After ≥12 Months):
- Red blood cell indices (RBC count, hemoglobin, hematocrit): These stabilize within 6 months and should be interpreted using affirmed gender ranges after 12 months 3, 2, 6
- Creatinine and creatinine clearance: Use affirmed gender reference ranges after 12 months of GAHT 3
- Liver enzymes (alkaline phosphatase, ALT, AST, GGT): These shift toward affirmed gender ranges 3
- QTc interval: Use female reference range for transgender women on feminizing therapy after 12 months 3
Values That Remain Sex-Assigned-at-Birth Dependent:
- Cardiac troponin: Use reference range from sex assigned at birth, as this depends on heart size, not hormonal milieu 3
- Prostate-specific antigen (PSA): For transgender women with low testosterone, lower the upper limit of normal to 1.0 ng/mL (rather than standard male range) 3
Values Without Sex-Specific Ranges:
- Electrolytes (sodium, potassium, chloride, bicarbonate) have no sex-specific reference ranges 3
- Blood urea nitrogen (BUN) has no sex-specific reference range 3
- Hemoglobin A1c has no sex-specific reference range 3
Special Monitoring Considerations
For Transgender Men on Testosterone:
- Monitor for erythrocytosis: Check hemoglobin and hematocrit regularly, as testosterone increases red blood cell production 3, 5
- If polycythemia develops, consider dose reduction, switching to transdermal administration, or therapeutic phlebotomy 3
- Monitor blood pressure: Testosterone may increase blood pressure 3
- Monitor lipids closely: Expect increased triglycerides and LDL, decreased HDL beyond the first year 3, 6
For Transgender Women on Estrogen:
- Monitor for venous thromboembolism risk factors: Estrogen increases VTE risk 1
- Thyroid function monitoring: Estrogen increases thyroid-binding globulin; patients on thyroid replacement may require dose adjustments 7
- Monitor free T4 and free T3 to maintain levels in acceptable range 7
- Monitor calcium levels: Use caution in patients with hypocalcemia 7
Critical Pitfalls to Avoid
Timing-Related Errors:
- Do not use affirmed gender reference ranges before 12 months of consistent therapy, as values are transitioning and may lead to misinterpretation 3, 4
- After discontinuation of GAHT for ≥3 months, revert to sex-assigned-at-birth reference ranges, as laboratory values return to baseline within approximately 10 weeks to 3 months 3, 6
Organ-Specific Exceptions:
- Never use affirmed gender reference for cardiac troponin, as this reflects heart size, not hormonal status—always use sex-assigned-at-birth reference 3
- For PSA in transgender women, do not use standard male reference ranges—use the lowered threshold of 1.0 ng/mL upper limit when testosterone is suppressed 3
Renal Function Assessment:
- Avoid using standard creatinine-based eGFR formulas without considering GAHT duration, as muscle mass changes affect creatinine generation 3
- Cystatin C-based eGFR is preferred when available, as it is less dependent on muscle mass 3
Drug Dosing Implications:
- For chemotherapy or renally-cleared medications, use affirmed gender for dosing calculations after ≥6-12 months of GAHT, as creatinine clearance and lean body mass correspond with gender identity 3
Documentation Requirements
Record the duration of GAHT, dose, and route of administration at each laboratory assessment, as these factors influence interpretation of results 3