Diagnosis of Hypogonadism in Men
April 2020
Volume 4, Issue 2

Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline

J Clin Endocrinol Metab. 2010;95(6):2536-2559

Introduction:  A Task Force was created by The Endocrine Society to provide guidelines for evaluating and treating androgen deficiency syndromes in adult men.

This summary will focus on the evaluation portion of the guidelines, including symptoms, factors that affect SHBG levels, and the diagnostic process.

Summary of Evidence-based Androgen Deficiency Syndromes Evaluation Guidelines
Signs and Symptoms
Because many of the signs and symptoms of androgen deficiency are non-specific and are modified by several factors (including age, comorbid illness, and previous testosterone therapy), diagnosing androgen deficiency can be difficult.

Therefore, the Task Force identified the following list of signs and symptoms that are suggestive of androgen deficiency in men:

  • Incomplete sexual development, eunuchoidism, aspermia
  • Reduced sexual desire (libido) and activity
  • Decreased spontaneous erections
  • Breast discomfort, gynecomastia
  • Loss of body (axially and pubic) hair, reduced shaving
  • Very small or shrinking testes (especially < 5 ml)
  • Inability to father children, low or zero sperm counts
  • Height loss, low trauma fracture, low bone mineral density
  • Reduced muscle bulk and strength
  • Hot flushes, sweats

The following are associated with androgen deficiency in men, but they are less specific than the above list:

  • Decreased energy, motivation, initiative, aggressiveness, self-confidence
  • Feeling sad or blue, depressed mood, dysthymia
  • Poor concentration and memory
  • Sleep disturbance, increased sleepiness
  • Mild anemia (normochromic, normocytic, in the female range)
  • Increased body fat, body mass index
  • Diminished physical or work performance

Conditions that Alter SHBG Concentrations
Since total testosterone levels are changed by SHBG alterations, it’s important to know what factors can change SHBG levels.

Conditions that decrease SHBG concentrations

  • Moderate obesity
  • Nephrotic syndrome
  • Hypothyroidism
  • Use of glucocorticoids, progestins, and androgenic steroids

Conditions that increase SHBG concentrations

  • Aging
  • Hepatic cirrhosis
  • Hyperthyroidism
  • Use of anticonvulsants
  • Use of estrogens
  • HIV infection

The Task Force provided the following guidelines for diagnosing androgen deficiency syndromes in men:

  • A diagnosis should be made only in those men who have consistent signs and symptoms as well as unequivocally low serum testosterone levels.
  • For those patients showing signs and symptoms suggestive of androgen deficiency, their serum testosterone levels should be measured.  If the patient has less specific signs and symptoms—in addition to the more specific signs and symptoms—his serum testosterone level should also be measured.  If he, however, does not have any signs and symptoms of androgen deficiency, his serum testosterone does not need to be measured.
  • Measurement of morning total testosterone should be done by a reliable assay.  This should be the first diagnostic test.
  • Confirming the diagnosis can be done by repeating the measurement of total testosterone.  For some patients, measuring free or bioavailable testosterone may also be done (using an appropriate assay). 
  • The diagnosis of androgen deficiency should not be made during acute or subacute illness.



The diagnosis and treatment of men with androgen deficiency is surrounded by controversy. A Task Force was created in 2005 to develop clinical guidelines, and they were published in 2006 and updated in 2010.

Based on these guidelines, the diagnosis of androgen deficiency must include the presence of low serum testosterone levels as well as consistent signs and symptoms.  Accurate initial testing involves a morning serum total testosterone level with a reliable assay.  Repeat testing is needed to confirm the diagnosis.

In men with borderline-low testosterone levels and in men who are suspected of having SHBG abnormalities (i.e., obesity, diabetes, glucocorticoid use, aging, liver disease, thyroid disease), it is important to check a free or bioavailable testosterone level. The analog or direct assay of free testosterone is not a reliable assay of free testosterone.

It is recommended that the evaluation of androgen deficiency not be performed during an acute or subacute illness.  Once the diagnosis is confirmed, LH and FSH levels should be checked to differentiate primary versus secondary hypogonadism.

Following these clinical practice guidelines will help to ensure the accurate diagnosis and treatment of men with androgen deficiency.

Next Article:
Toward Excellence in Testosterone Testing: A Consensus Statement
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