What exercises are recommended for a male patient with confirmed hypogonadism (low testosterone) before starting testosterone replacement therapy (TRT)?

Baseline Laboratory Workup Before Starting Testosterone Replacement Therapy

Before initiating testosterone therapy in a male patient with confirmed hypogonadism, you must obtain morning total testosterone levels on two separate occasions (drawn between 8-10 AM), measure LH and FSH to distinguish primary from secondary hypogonadism, check baseline hematocrit/hemoglobin, obtain PSA and perform digital rectal examination in men over 40 years, and measure free testosterone by equilibrium dialysis if total testosterone is borderline. 1, 2

Essential Pre-Treatment Laboratory Tests

Testosterone Confirmation Testing

• Repeat morning total testosterone measurements (8-10 AM) on at least two separate occasions to establish persistent hypogonadism, as single measurements are insufficient due to assay variability and diurnal fluctuation 1, 3
• Testosterone levels below 300 ng/dL on both occasions confirm biochemical hypogonadism 1, 2
• Measure free testosterone by equilibrium dialysis in addition to total testosterone when total testosterone is borderline (near the lower limit of normal) 1, 2
• Obtain sex hormone-binding globulin (SHBG) levels to distinguish true hypogonadism from low SHBG-related decreases in total testosterone 1

Gonadotropin Assessment

• Measure serum LH and FSH concentrations after confirming low testosterone to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1, 3
• Elevated LH/FSH with low testosterone indicates primary (testicular) hypogonadism 1
• Low or low-normal LH/FSH with low testosterone indicates secondary (hypothalamic-pituitary) hypogonadism 1
• This differentiation has critical treatment implications, including fertility preservation and treatment selection 1

Hematologic Baseline

• Document baseline hematocrit or hemoglobin before initiating testosterone therapy to monitor for potential erythrocytosis during treatment 4, 1
• Hematocrit >54% is an absolute contraindication to starting testosterone therapy 1, 2

Prostate Cancer Screening (Men ≥40 Years)

• Perform digital rectal examination to assess for palpable prostate nodules or induration 4, 2
• Measure baseline PSA level in men over 40 years 4, 1
• PSA >4.0 ng/mL requires urologic evaluation and documented negative prostate biopsy before initiating therapy 4
• PSA >3.0 ng/mL in men at increased risk (African Americans, first-degree relative with prostate cancer) requires further urological evaluation before starting therapy 2

Additional Workup for Secondary Hypogonadism

If LH and FSH are low or low-normal, indicating secondary hypogonadism, additional testing is mandatory:

• Measure serum prolactin to investigate for hyperprolactinemia, which can cause secondary hypogonadism 1
• Measure iron saturation to evaluate for hemochromatosis 1
• Consider pituitary function testing and MRI of the sella turcica to identify etiology of hypothalamic/pituitary dysfunction 1

Critical Fertility Assessment

Before prescribing testosterone, explicitly confirm the patient does not desire fertility in the near term, as testosterone therapy causes azoospermia and is absolutely contraindicated in men seeking fertility preservation. 1, 2

• For men with secondary hypogonadism who desire fertility, gonadotropin therapy (recombinant hCG plus FSH) is mandatory and testosterone is contraindicated 1
• Men with primary hypogonadism cannot achieve fertility restoration even with gonadotropin therapy 1

Common Pitfalls to Avoid

• Never diagnose hypogonadism based on a single testosterone measurement due to assay variability and diurnal fluctuation 1, 3
• Never start testosterone without measuring LH and FSH, as this distinction determines whether fertility preservation is possible 1
• Never assume the patient doesn't want children without explicit discussion, as testosterone causes prolonged azoospermia that may persist for months after discontinuation 1
• Never skip prostate evaluation in men over 40, as monitoring for prostate cancer is mandatory given concerns about potential stimulation of occult cancer 4
• Never attempt to diagnose the type of hypogonadism while the patient is already on testosterone therapy, as exogenous testosterone suppresses LH and FSH, making results misleading 1

Baseline Monitoring Timeline

Once testosterone therapy is initiated:

• Measure testosterone levels 2-3 months after treatment initiation and after any dose change 1, 5
• For injectable testosterone (cypionate/enanthate), measure levels midway between injections (days 5-7 after injection), targeting mid-normal values of 500-600 ng/dL 4, 1
• Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 1
• Monitor hematocrit periodically and withhold treatment if >54%, considering phlebotomy in high-risk cases 4, 1
• Monitor PSA levels in men over 40 years, with urologic referral for biopsy if PSA increases >1.0 ng/mL during the first 6 months or >0.4 ng/mL per year thereafter 4