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How low testosterone is diagnosed, and why two morning tests matter

Low testosterone is diagnosed from two things together: symptoms and signs that fit, and blood tests that are clearly and consistently low. The Endocrine Society 2018 guideline recommends confirming the diagnosis by repeating a fasting, morning total testosterone test. The Depo-Testosterone (testosterone cypionate) label also asks for morning levels on at least two separate days, both below the normal range, before treatment starts.

What hypogonadism means

MedlinePlus defines hypogonadism as the sex glands, the testes in men, producing little or no hormones. It can be primary, starting in the testes, or secondary (also called central), starting in the pituitary or hypothalamus.

MedlinePlus lists causes of primary hypogonadism including autoimmune disorders, genetic disorders such as Klinefelter syndrome, infection, iron excess, liver and kidney disease, radiation, surgery and trauma. Causes of central hypogonadism it lists include medicines such as glucocorticoids and opiates, stopping anabolic steroids, pituitary bleeding or tumors, rapid weight loss, nutritional deficiencies and trauma.

Why symptoms alone are not enough

MedlinePlus lists symptoms in men as breast enlargement, muscle loss and low libido, and says hypogonadism may cause impotence, infertility, osteoporosis and weakness. But the Endocrine Society guideline text says the symptoms and signs of testosterone deficiency are nonspecific and are modified by age and comorbid illness.

Population studies show the gap between a low number and a real deficiency. In the Boston Area Community Health Survey of 1,475 randomly selected men aged 30 to 79, about 24% had total testosterone below 300 ng/dL, but the crude prevalence of symptomatic androgen deficiency was 5.6%. Many men with low testosterone had no symptoms (47.6% of men aged 50 and older).

In the European Male Aging Study, a random sample of 3,369 men aged 40 to 79, only three sexual symptoms had a syndromic association with low testosterone: poor morning erection, low sexual desire and erectile dysfunction.

Why the test is repeated in the morning

The Endocrine Society guideline text says testosterone peaks in the morning. It also says about 30% of men with an initial value in the hypogonadal range have a normal value when it is measured again.

That is why the guideline recommends a fasting, morning total testosterone measured with an accurate and reliable assay as the first test, then a repeat morning fasting test to confirm. For men whose total testosterone is near the lower limit of normal, or who have a condition that alters sex hormone-binding globulin, it recommends a free testosterone level by equilibrium dialysis or an accurate formula.

QuestionWhat the source says
How many tests?The Endocrine Society recommends repeating the morning fasting total testosterone to confirm. The cypionate label asks for morning levels on at least two separate days, both below the normal range.
What time of day?Morning, when the guideline text says testosterone peaks.
Should all men be screened?The Endocrine Society recommends against routine screening of men in the general population.
When should testing wait?Not during or while recovering from an acute illness, or while using short-term medicines such as opioids that suppress testosterone.

Things that can lower a reading

The guideline text says testosterone levels are affected by age, obesity, diabetes and sleep disorders including obstructive sleep apnea, and it lists severe obesity among causes of secondary hypogonadism. Levels may also be affected by acute illness, nutritional deficiency and certain medications, such as opioids.

MedlinePlus notes that testosterone declines with age, that the normal range is lower in men aged 50 to 60 than in men aged 20 to 30, and that test interpretation in older or obese men can be difficult.

What the guidelines say about the decision

Where deficiency is confirmed, the Endocrine Society recommends therapy only after discussing the potential benefits and risks of therapy and of monitoring, and involving the patient in the decision. It suggests aiming for mid-normal levels during treatment, with a monitoring plan covering symptoms, side effects, adherence, serum testosterone, hematocrit and prostate cancer risk during the first year.

The PubMed abstract of the 2018 AUA guideline says care should focus on accurate assessment of total testosterone, symptoms and signs, plus proper on-treatment monitoring. A licensed provider decides whether a man's results and symptoms add up to a diagnosis.

What this does not tell you

The Endocrine Society and AUA guidelines are professional recommendations, not laws, and the AUA points here come only from its published abstract. The survey figures describe groups of men in Boston and Europe; they do not show what any one man's result means.

The European Male Aging Study proposed defining late-onset hypogonadism as at least three sexual symptoms plus total testosterone below 11 nmol/L (3.2 ng/mL) and free testosterone below 220 pmol/L (64 pg/mL). That is a research proposal, not a rule. This article does not set a cut-off for anyone, and it does not replace a review by a licensed provider.

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