What is a proper workup for low testosterone in men?

Low testosterone is diagnosed on symptoms and consistent biochemistry, not on one number. The 2018 Endocrine Society clinical practice guideline recommends making the diagnosis "only in men with symptoms and signs consistent with testosterone deficiency and unequivocally and consistently low serum T concentrations". It recommends measuring fasting morning total testosterone as the initial test, and then "confirming the diagnosis by repeating the measurement of morning fasting total T concentrations". Two samples, both morning, both fasting.

Why two morning fasting samples

Testosterone follows a daily rhythm with a peak in the early morning, and a single afternoon sample can read low in a man with entirely normal production. Food lowers testosterone acutely, which is why fasting matters. Acute illness, sleep deprivation and recent heavy exercise all suppress it temporarily. Repeating the test on a separate morning removes most of these false positives, and a meaningful proportion of men with one low result have a normal second one.

The threshold to use

The Endocrine Society guideline uses a harmonised reference range derived from healthy nonobese young men of 264 to 916 ng/dL, with the lower limit of 264 ng/dL functioning as the practical cut-off. The American Urological Association uses 300 ng/dL. Free testosterone should be measured by equilibrium dialysis or calculated when sex hormone binding globulin is altered, for example in obesity, diabetes or glucocorticoid use, or when total testosterone sits in the borderline zone of roughly 200 to 400 ng/dL.

What else belongs in the workup

Once low testosterone is confirmed, LH and FSH separate primary testicular failure, where they are high, from secondary or pituitary causes, where they are low or inappropriately normal. Secondary hypogonadism prompts prolactin measurement, iron studies for haemochromatosis, and pituitary imaging when testosterone is very low or other pituitary hormones are abnormal. Obstructive sleep apnoea, opioid use, high alcohol intake, anabolic steroid history and untreated obesity are all reversible contributors that should be addressed before committing to lifelong therapy.

If you have been offered testosterone after a single afternoon blood test, ask for a repeat morning fasting sample, plus LH, FSH and prolactin, before starting. Fertility should also be discussed first: exogenous testosterone suppresses sperm production, and that suppression can persist after stopping.