Laboratory Tests Required Before Starting Testosterone Replacement Therapy

Essential Baseline Laboratory Tests

The American Urological Association recommends measuring morning total testosterone levels on at least two separate occasions to confirm testosterone deficiency 1
The American Urological Association suggests measuring luteinizing hormone (LH) levels to establish the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 2
The American Urological Association recommends baseline measurement of hemoglobin/hematocrit to monitor for polycythemia, and to withhold therapy if hematocrit exceeds 50% 2
The American Urological Association requires prostate-specific antigen (PSA) measurement in men over 40 years of age to exclude occult prostate cancer 3

The American Urological Association recommends measuring serum prolactin in patients with low testosterone combined with low or low/normal LH levels to screen for hyperprolactinemia 2
The American Urological Association suggests measuring follicle-stimulating hormone (FSH) in men interested in preserving fertility to assess reproductive health status 3
The American Urological Association recommends measuring estradiol in patients who present with breast symptoms or gynecomastia prior to starting therapy 3
The American Heart Association recommends assessing cardiovascular risk factors, including lipid profile, to evaluate the risk of cardiovascular disease 4

The American Urological Association suggests considering pituitary MRI for patients with total testosterone levels <150 ng/dL combined with low or low/normal LH, regardless of prolactin levels, to rule out pituitary tumors 2
The American Urological Association recommends considering semen analysis for patients interested in preserving fertility 3
The American Heart Association recommends evaluating both fixed (e.g., older age) and modifiable (e.g., dyslipidemia, hypertension, diabetes, smoking) risk factors for cardiovascular disease 3

The Endocrine Society recommends scheduling a follow-up visit 1-2 months after initiation of testosterone replacement therapy to assess efficacy 5
The Endocrine Society suggests monitoring serum testosterone levels, hemoglobin/hematocrit, PSA levels, and performing digital rectal examination at each follow-up visit 5

The Endocrine Society recommends interpreting blood test results based on the interval since the most recent injection (peak levels occur 2-5 days after injection) for men receiving injection therapy 5
The American Urological Association suggests considering urologic referral for possible biopsy for patients with an increase in PSA of more than 1.0 ng/mL during the first six months of treatment or more than 0.4 ng/mL per year thereafter 6
The American Urological Association recommends counseling patients on the risk of reduced fertility associated with testosterone replacement therapy 4
The American Urological Association warns that injectable testosterone is associated with the greatest treatment-induced increases in hemoglobin/hematocrit, increasing the risk of polycythemia 3

The American Urological Association recommends obtaining a second PSA measurement to confirm any initial elevation before proceeding with testosterone therapy, because a single value can be falsely high due to recent ejaculation, prostate manipulation, or infection. (expert consensus) 9
A PSA level greater than 4.0 ng/mL is the traditional threshold that mandates further prostate evaluation (repeat testing, DRE, possible biopsy) prior to initiating testosterone replacement. (clinical guideline) 10
An abnormal digital rectal examination (e.g., palpable nodule, asymmetry, increased firmness) requires a prostate biopsy regardless of PSA level. (clinical guideline) 11
When two PSA measurements raise suspicion for cancer, reflex testing such as the 4K score or Prostate Health Index (phi) may be employed to improve specificity and reduce unnecessary biopsies. (expert consensus) 9
If PSA remains elevated after repeat testing or the DRE is abnormal, a prostate biopsy (with or without multiparametric MRI) should be performed before testosterone therapy is considered. (expert consensus) 11
Testosterone therapy is absolutely contraindicated until prostate cancer has been definitively excluded by biopsy or appropriate imaging. (clinical principle) 11
Baseline PSA screening is mandatory for all men ≥ 40 years before starting testosterone replacement. (guideline recommendation) 12

After a negative prostate biopsy, PSA should be re‑measured at 3–6 months following initiation of testosterone therapy and then annually thereafter. (guideline recommendation) 10
A physiologic PSA rise of approximately 0.30–0.43 ng/mL is expected after testosterone initiation and does not, by itself, indicate malignancy. (clinical observation) 13
A digital rectal examination should be performed at every follow‑up visit to detect any new prostate abnormalities. (guideline recommendation) 11

Increase of ≥ 1.0 ng/mL in PSA within the first 6 months of testosterone therapy warrants urologic referral and consideration of repeat biopsy. (guideline threshold) 10
After the initial 6 months, a rise of ≥ 0.4 ng/mL per year should prompt repeat evaluation. (guideline threshold) 10
A PSA rise of 0.7–0.9 ng/mL over a single year should lead to a repeat PSA in 3–6 months; any further increase then triggers biopsy. (guideline algorithm) 13
Any new abnormality on DRE (new nodule, asymmetry, increased firmness) at any time during therapy mandates referral for biopsy. (guideline algorithm) 11

In men with a history of treated prostate cancer, testosterone therapy should be approached with extreme caution and preferably only within a research protocol or specialized clinical trial setting. (expert consensus) 9

The 2018 American Urological Association guideline provides the most current and authoritative recommendations for managing testosterone replacement in men with elevated PSA, emphasizing repeat PSA testing, reflex testing, and mandatory cancer exclusion before therapy. (expert consensus, high‑quality guideline) 9