Watch the whiteboard explainer (Part 2, the Workup):

Table of Contents

The Key Takeaways

  • One blood test is not a diagnosis. Testosterone should be drawn on two separate mornings, fasting, between 7 and 10 AM, because it peaks in the morning and falls through the day. A 2 PM lab is close to meaningless (Bhasin et al., J Clin Endocrinol Metab 2018).

  • The “low” cutoff depends on who you ask. The AUA uses under 300 ng/dL, the Endocrine Society under 264, the UK under 230. Between roughly 230 and 350 you need symptoms plus a full panel, not just a number (Mulhall et al., AUA 2018; Hackett et al., BSSM 2017).

  • Free Testosterone can provide clarity on if a patient with borderline testosterone would benefit from treatment. Testosterone is bound to proteins called SHBG and albumin and the unbound free circulating testosterone is biologically active The same total of 350 can be perfectly normal in one man and clearly low in another (Vermeulen et al., 1999).

  • Estrogen is an essential hormone in men. More than 80% of a man’s estradiol is made from his own testosterone, and that estradiol protects his bones, controls fat gain, and drives libido. (Finkelstein et al., N Engl J Med 2013).

  • A brain MRI is rarely needed. Imaging the brain is recommend in the following scenarios: a very low testosterone (<150) with low or normal LH, a high prolactin, or the symptoms of a pituitary mass. (AUA and Endocrine Society guidelines).

Want to know the science? Keep reading below.

In Part 1 we covered the causes of low testosterone, and discussed the impact of sleep, weight, and stress. This week is the part almost nobody does correctly: the workup.

The workup is simply the set of labs and questions that separate real low testosterone from a number that only looks low. Done right, it is two morning blood draws plus a full hormone panel, read in the context of your symptoms, before anyone reaches for a prescription. That sounds obvious. In practice, most men are diagnosed off a single number drawn at the wrong time of day, and that is where the trouble starts.

The 5 rules of testing testosterone right

Rule 1: Draw it in the morning, fasting, 7 to 10 AM. Testosterone peaks in the early morning and drops through the afternoon, so a lab drawn at 2 PM can read low on a perfectly normal man. Timing is not a detail here, it is the whole test.

Rule 2: Confirm it twice. Your level bounces from day to day. One low result is not a diagnosis. A real diagnosis needs two low readings on two separate mornings.

Rule 3: Testosterone levels can be affected by many factors. An acute illness, a single bad night of sleep, or medications like opioids, steroids, and certain antidepressants can temporarily drop your testosterone. Test during one of those and you will get a low number that means nothing. Wait until things settle.

Rule 4: Different guidelines use different thresholds . There is no single magic number. The AUA calls low under 300 ng/dL, the Endocrine Society under 264, and the UK under 230. If you land in the gray zone of roughly 230 to 350, use a calculated free Testosterone to guide management.

Rule 5: Order the whole panel, not just total testosterone. Total T by itself is not enough. A proper workup includes total testosterone, LH and FSH, SHBG, albumin, a calculated free testosterone, prolactin, and estradiol. Each one tells you something the total number hides.

Total testosterone can lie: the SHBG trap

Your testosterone travels through the blood in two states: bound to proteins, and free. Only the free unbound testosterone is biologically active. A protein made by your liver called SHBG (sex hormone binding globulin) grabs testosterone and holds it tightly, so the more SHBG you have, the less of your testosterone is usable, even when the total looks fine.

Picture two men with the exact same total testosterone of around 350. The first is a heavy 40 year old. Obesity, diabetes, and a low thyroid all drop SHBG, so he has fewer carriers and plenty of free testosterone. His total reads low, but his free T is normal, and his real problem is not his testosterone.

The second is a lean 65 year old. Aging, liver disease, and a high thyroid all raise SHBG, so his testosterone is locked up and barely any is free. His total reads a reassuring 380, but his free T is genuinely low. The headline number hid a real problem.

Same total number. Opposite reality. That is why, when the total testosterone looks borderline, the free testosterone is the number that actually settles it. Free T is usually not measured directly and lab assays are inaccurate. Instead, it should be calculated from your total testosterone, SHBG, and albumin (Vermeulen et al., J Clin Endocrinol Metab 1999).

Estradiol is not the enemy

There is a myth that estrogen is a problem for men and lower is always better. It is wrong, and chasing a low estradiol can hurt you.

More than 80% of a man’s estradiol is made from his own testosterone, converted by an enzyme called aromatase, mostly in fat tissue. That estradiol is not a waste product. It does three real jobs: it builds and protects bone (that is estradiol’s work, not testosterone’s), it helps prevent fat gain, and, alongside testosterone, it drives libido and erectile function (Finkelstein et al., N Engl J Med 2013).

So when you see a normal estradiol on a man’s panel, that is usually estradiol doing its job. The target is balance, not suppression.

When you actually need a brain scan

The brain runs the whole system, so a natural worry is whether low testosterone means something is wrong at level of the brain. Almost always, the answer is no, and a pituitary MRI is not a routine part of the workup. There are only three specific triggers.

First, a very low total testosterone, under about 150 ng/dL, paired with a low or normal LH. That pattern points to the brain rather than the testicles, and a structural cause has to be ruled out.

Second, a prolactin that stays high without an obvious medication or other explanation, which can signal a small hormone secreting tumor and should be confirmed on a repeat test.

Third, the symptoms of a mass pressing on the pituitary: new headaches, changes in your vision, or several pituitary hormones dropping at once. Any one of these earns a scan. Short of them, a scan is not part of the workup.

You almost certainly know a man who was started on testosterone for the wrong reason or thinks they need testosterone therapy. Please forward this to him. It is exactly what he needs to walk into that appointment asking the right questions.

Catch up on the series

References

Bhasin et al., J Clin Endocrinol Metab 2018 · Mulhall et al., AUA Guideline, J Urol 2018 · Hackett et al., BSSM Guidelines, J Sex Med 2017 · Vermeulen, Verdonck & Kaufman, J Clin Endocrinol Metab 1999 · Finkelstein et al., N Engl J Med 2013 · Wu et al., N Engl J Med 2010 · Travison et al., J Clin Endocrinol Metab 2017 · Diver et al., Clin Endocrinol (Oxf) 2003 · Brambilla et al., J Clin Endocrinol Metab 2007 · Rosner et al., J Clin Endocrinol Metab 2007 · Corona et al., Eur J Endocrinol 2013

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