When should serum testosterone levels be tested in the context of Hormone Replacement Therapy (HRT)?

Serum Testosterone Testing in Hormone Replacement Therapy (HRT)

Serum testosterone levels should be tested before initiating HRT to confirm hypogonadism, then 2-3 months after treatment initiation or dose changes, and subsequently every 6-12 months once stable levels are achieved. 1, 2

Initial Testing Before Starting HRT

• Confirm diagnosis of hypogonadism by ensuring serum testosterone concentrations have been measured in the morning on at least two separate days and are below the normal range 2
• Measure luteinizing hormone (LH) levels to help establish the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 1
• For patients with low testosterone and low/normal LH levels, measure serum prolactin to screen for hyperprolactinemia 1
• Measure hemoglobin/hematocrit as baseline before initiating therapy (if Hct exceeds 50%, consider withholding therapy until etiology is investigated) 1
• For men over 40 years, measure PSA to exclude occult prostate cancer 1
• For men with breast symptoms or gynecomastia, measure serum estradiol before starting therapy 1
• For men interested in fertility, measure follicle-stimulating hormone (FSH) to assess reproductive health status 1

Follow-up Testing After Starting HRT

Timing of Follow-up Tests

• First follow-up: Test testosterone levels 2-3 months after treatment initiation or any dose change 1
• Once stable levels are confirmed on a given dose, monitor every 6-12 months 1

Timing Based on Testosterone Formulation

• For injectable testosterone:

  • Measure levels midway between injections, targeting a mid-normal value (500-600 ng/dL) 1
  • This helps avoid measuring at peak levels (occurring 2-5 days post-injection) or trough levels (10-14 days post-injection) 1

• For transdermal preparations (gels, patches):

  • Levels can be measured at any time, but be aware that:
    • Peak values occur 6-8 hours after patch application 1
    • Testosterone concentrations can vary substantially with gel use 1

Monitoring Parameters Beyond Testosterone Levels

• Hemoglobin/hematocrit: Monitor at each follow-up visit; if Hct exceeds 54% while on therapy, intervention is warranted (dose reduction or temporary discontinuation) 1
• PSA: Monitor at each follow-up visit, particularly in men over 40 years 1
  • Consider prostate biopsy for PSA increases of more than 1.0 ng/mL during first six months or more than 0.4 ng/mL per year thereafter 1
• Clinical response: Assess symptomatic improvement in erectile function, libido, energy levels, mood, etc. 1
• Cardiovascular risk factors: Regularly assess modifiable risk factors (dyslipidemia, hypertension, diabetes, smoking) 1

Special Considerations

• For men on testosterone therapy who are planning future fertility, testosterone should be discontinued well in advance of conception attempts 1
• Injectable testosterone is associated with greater treatment-induced increases in hemoglobin/hematocrit compared to other formulations 1
• Patients with persistently high prolactin levels should be referred to an endocrinologist for further evaluation 1
• Men with total testosterone levels <150 ng/dL combined with low/normal LH should undergo pituitary MRI regardless of prolactin levels 1

Common Pitfalls to Avoid

• Failing to confirm low testosterone with two morning measurements before initiating therapy 2
• Not adjusting timing of blood draws based on testosterone formulation, leading to misleading results 1
• Inadequate monitoring after initiating therapy (only 36% of men on testosterone therapy have follow-up levels checked in real-world practice) 3
• Insufficient dose adjustment (49% of men remain biochemically hypogonadal after starting therapy due to non-compliance or inadequate dosing) 3
• Not monitoring for polycythemia, which is a common side effect, particularly with injectable formulations 1