Which baseline laboratory tests and follow‑up monitoring (including frequency) are recommended for patients on hormone replacement therapy, covering estrogen and testosterone regimens?

Laboratory Monitoring for Hormone Replacement Therapy

Testosterone Replacement Therapy

For men on testosterone replacement therapy, monitor testosterone levels, PSA, hematocrit/hemoglobin, and digital rectal examination every 3-6 months for the first year, then annually thereafter. 1

Baseline Testing (Before Initiation)

• Testosterone level (morning sample) 1
• PSA (prostate-specific antigen) 1
• Hematocrit or hemoglobin 1
• Digital rectal examination 1
• Prostate biopsy if PSA >4.0 ng/mL or abnormal digital rectal examination 1
• Baseline voiding history (assess for benign prostatic hypertrophy) 1
• History of sleep apnea 1

Follow-Up Monitoring Schedule

• At 1-2 months: Efficacy evaluation with testosterone level and dosage adjustment for suboptimal response 1
• Every 3-6 months for the first year: Complete monitoring panel 1
• Annually thereafter: Complete monitoring panel 1

Specific Parameters to Monitor

• Testosterone levels: Ensure therapeutic range is achieved 1
• Hematocrit/hemoglobin: Check for polycythemia development 2
• PSA monitoring: Critical for prostate cancer surveillance 1
  • Perform prostate biopsy if PSA rises above 4.0 ng/mL 1
  • Consider biopsy if PSA increases by ≥1.0 ng/mL in any year 1
  • If PSA rises by 0.7-0.9 ng/mL, repeat in 3-6 months and biopsy for any further increase 1
• Digital rectal examination: Assess for nodules, asymmetry, or increased firmness 1
• Urinary symptoms: Monitor for development or worsening 1, 2
• Sleep apnea: Assess for exacerbation 1
• Serum cholesterol: May increase during therapy 2

Laboratory Changes Expected

• Red blood cell indices increase within 6 months and remain stable long-term 3, 4
• Hemoglobin and hematocrit increase (effect size d >0.6) 4
• Creatinine levels increase within 6 months 3, 4
• Triglycerides increase and HDL decreases in transgender men 4
• Liver enzymes (ALT, AST) may increase beyond 1 year 3

Estrogen Replacement Therapy

For patients on estrogen therapy, monitor thyroid function in those on thyroid replacement, check lipid panels, and assess blood pressure regularly, with baseline mammography required before initiation. 5, 6

Baseline Testing (Before Initiation)

• FSH and estradiol to confirm menopausal status 6
• Mammography (essential for malignancy exclusion) 6
• Lipid profile (cholesterol, triglycerides, HDL, LDL) 5, 6
• Thyroid function tests if on thyroid replacement therapy 5
• Blood pressure 5
• Liver function tests if history of liver disease 5

Follow-Up Monitoring Schedule

• Day 21 of each therapy cycle for the first 6 months 7
• Every 3-6 months initially, then adjust based on clinical response 5
• Three months after discontinuing therapy to assess return to baseline 7

Specific Parameters to Monitor

• Thyroid function: Patients on thyroid replacement therapy require monitoring to maintain free thyroid hormone levels in acceptable range 5
  • Estrogen increases thyroid-binding globulin (TBG) 5
  • May require increased thyroid hormone doses 5
  • Free T4 and free T3 remain unaltered despite changes in total hormone levels 5
• Blood pressure: Monitor at regular intervals 5
• Lipid profile: Plasma cholesterol decreases on HRT 7
  • Increased HDL and HDL2 subfraction concentrations 5
  • Reduced LDL cholesterol 5
  • Increased triglyceride levels 5
• Glucose tolerance: May be impaired 5
• Coagulation parameters: Monitor prothrombin time, partial thromboplastin time if clinically indicated 5

Laboratory Changes Expected in Transgender Women

• Red blood cell indices, hemoglobin, and hematocrit decrease within 6 months 3, 4
• Creatinine levels decrease (effect size d >0.6) 4
• HDL increases and platelets increase beyond the first year 3
• Calcium, albumin, and alkaline phosphatase decrease significantly 4
• Most analytes stabilize within 6 months, though some continue changing long-term 3
• Return to baseline occurs around 10 weeks after discontinuation 3

Critical Monitoring Considerations

• Avoid routine monitoring with serum hormone levels (estradiol, FSH) to guide dosing; use clinical response instead 5
• Triglyceride monitoring is essential in patients with pre-existing hypertriglyceridemia due to risk of pancreatitis 5
• Liver function monitoring only needed if impaired liver function or history of cholestatic jaundice 5