Are requests for Free and Total Testosterone, Sex Hormone-Binding Globulin (SHBG), Follicle-Stimulating Hormone (FSH), Estradiol (E2), Prolactin, Cortisol, Insulin-like Growth Factor 1 (IGF-1), Dehydroepiandrosterone Sulfate (DHEAS), and Progesterone tests reasonable for evaluating suspected low testosterone levels and related hormonal imbalances in a patient with symptoms of fatigue, low libido, low motivation, mood swings, and difficulty concentrating?

Evaluation of Requested Hormone Testing for Suspected Low Testosterone

The requested hormone panel is largely reasonable and aligns with guideline-based evaluation of suspected testosterone deficiency, though some tests (IGF-1, DHEAS, Progesterone) are not routinely indicated unless specific clinical features suggest additional endocrine pathology. 1, 2

Core Essential Tests (Strongly Recommended)

The following tests are guideline-supported and directly address the patient's presentation:

Primary Testosterone Assessment

• Total Testosterone (morning, repeated on two separate occasions) is the foundational diagnostic test, with levels <300 ng/dL supporting the diagnosis of testosterone deficiency 1, 2
• Free Testosterone is essential when total testosterone is near the lower limit of normal or when SHBG abnormalities are suspected, which is common in patients with fatigue and metabolic concerns 1, 2
• SHBG measurement is particularly important because variations in SHBG can significantly affect total testosterone interpretation—low SHBG (common in obesity and metabolic syndrome) can lower total testosterone while free testosterone remains normal 1, 2

Secondary Hormonal Evaluation

• LH (Luteinizing Hormone) is strongly recommended to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism, which fundamentally changes management 1, 2
• FSH (Follicle-Stimulating Hormone) helps further characterize the type of hypogonadism and is part of the standard workup when testosterone is confirmed low 1, 2
• Prolactin should be measured if testosterone is low with low or low-normal LH levels, as hyperprolactinemia is a treatable cause of secondary hypogonadism 1, 2
• Estradiol (E2) is indicated if breast symptoms or gynecomastia develop, but can also be informative in the initial workup since increased aromatization of testosterone to estradiol (particularly in adipose tissue) can suppress LH secretion and contribute to hypogonadism 1, 2

Tests with Limited or Conditional Indication

Cortisol

• Morning cortisol is not routinely part of testosterone deficiency evaluation unless there are specific symptoms suggesting adrenal insufficiency (hypotension, hyperpigmentation, salt craving) or Cushing's syndrome (central obesity, striae, easy bruising) 1
• However, given the patient's fatigue and difficulty concentrating, a single morning cortisol or ACTH stimulation test may be reasonable if clinical suspicion exists for adrenal pathology 1

IGF-1 (Insulin-like Growth Factor 1)

• IGF-1 is not part of standard testosterone deficiency workup 1, 2
• This test is indicated only if growth hormone deficiency is suspected (history of pituitary disease, severe fatigue with other pituitary hormone deficiencies, or if testosterone is <150 ng/dL with low LH suggesting broader pituitary dysfunction) 1

DHEAS (Dehydroepiandrosterone Sulfate)

• DHEAS is not routinely recommended in testosterone deficiency evaluation 1, 2
• This test may be considered if adrenal insufficiency is suspected or in cases of unexplained severe fatigue with other endocrine abnormalities, but it does not change management of testosterone deficiency itself 1

Progesterone

• Progesterone has no role in the evaluation of male hypogonadism and is not indicated 1, 2
• This test is relevant only in female reproductive endocrinology or in rare cases of congenital adrenal hyperplasia evaluation 1

Critical Implementation Details

Timing and Methodology

• All testosterone measurements must be drawn between 8 AM and 10 AM on two separate occasions, preferably using the same laboratory and methodology 1, 2
• Free testosterone should be measured by equilibrium dialysis (the gold standard method) rather than calculated values when possible 1, 3

Diagnostic Algorithm

1. Measure morning total testosterone on two separate occasions 1, 2
2. If total testosterone is <300 ng/dL on both occasions, measure LH, FSH, and free testosterone 1, 2
3. If LH/FSH are low or low-normal, measure prolactin 1, 2
4. If prolactin is elevated, repeat to confirm and consider pituitary MRI if testosterone <150 ng/dL 2
5. Measure SHBG to interpret total vs. free testosterone discrepancies 1, 2
6. Consider estradiol measurement given its role in negative feedback on the hypothalamic-pituitary axis 1

Common Pitfalls to Avoid

• Do not rely on a single testosterone measurement—day-to-day variations are significant and require confirmation 1, 2
• Do not use screening questionnaires as substitutes for laboratory testing—they have variable sensitivity and specificity 1, 2
• Do not overlook SHBG variations—particularly in patients with obesity, metabolic syndrome, or thyroid disorders, as these conditions alter SHBG and affect total testosterone interpretation 1
• Do not measure free testosterone by direct immunoassay—this method is unreliable; use equilibrium dialysis or calculate from total testosterone and SHBG using validated formulas 3

Recommended Testing Panel

Tier 1 (Essential):

• Total Testosterone (morning, ×2 occasions) 1, 2
• Free Testosterone 1, 2
• SHBG 1, 2
• LH 1, 2
• FSH 1, 2
• Prolactin 1, 2

Tier 2 (Reasonable to include):

• Estradiol (E2) 1, 2

Tier 3 (Consider only with specific clinical indications):

• Cortisol (if adrenal pathology suspected) 1
• IGF-1 (if pituitary dysfunction suspected) 1
• DHEAS (if adrenal insufficiency suspected) 1

Not indicated:

• Progesterone 1, 2