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This Month's Question

What steps do you take to diagnose hypogonadism?

Response by Glenn R. Cunningham, MD, Posted 06/15/07

Hypogonadism is not an easily defined diagnosis. Physical signs and symptoms, as well as laboratory assays, are needed to make the diagnosis. The difficulties with diagnosis are that many signs and symptoms are nonspecific, and many testosterone (T) assays are not precise.

The clinical presentation of male hypogonadism will vary depending on the age of the patient at the onset of the disorder. Signs and symptoms of T deficiency are common in younger men with hypogonadism and vary by age and comorbid conditions in older men.

Signs and Symptoms of T Deficiency1
  • Decreased sexual desire and sexual activity
  • Fewer morning or spontaneous erections
  • Gynecomastia
  • Loss of body hair, less shaving
  • Height loss, low trauma fracture, low bone mineral density
  • Reduced muscle bulk and strength
  • Hot flashes, sweats

Clinicians should also consider hypogonadism when patients present with less significant specific signs and symptoms in addition to those listed above.

Less Specific Signs and Symptoms Associated With T Deficiency1

  • Lower energy, motivation
  • Sadness, depressed mood
  • Poor concentration and memory
  • Sleep disturbance
  • Increased body fat or body mass index

Assays for plasma testosterone pose a number of challenges. T levels in men vary depending on2

  • Age
  • Comorbid conditions
  • Time of day
  • Assay interference by other circulating steroids

In addition, all but 1% to 3% of T is bound to plasma proteins, raising questions about whether total T (TT) or free (bioavailable) T (FT) is the most clinically useful measure. Practically, FT correlates better than TT with the patient’s hypogonadal condition.3

T levels preferably are measured in the mornings, when they are at their peak; however, this may not be feasible in clinical practice. For example, if I see a patient in the afternoon, I will order a TT level. If the result comes back low, then I’ll follow up with an early morning sample. If the patient has characteristics suggesting that he may have altered sex hormone-binding globulin (SHBG) levels, then I would also order an FT level.

Conditions Associated With Decreased SHBG Concentrations1

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

FT level can be measured by equilibrium dialysis, or FT can be calculated by knowing the TT and SHBG levels. The laboratory may do the calculation, or a calculator is available for use on the ISSAM Website (http://www.issam.ch/). The calculated FT is a rapid, simple, and reliable value measurement that is more suited to clinical practice.3

Normal and low normal T levels are undefined and remain debatable. The Endocrine Society position paper states the following2

  • TT >320 ng/dL is considered normal
  • TT <200 ng/dL is diagnostic for hypogonadism
  • TT 200 to 320 ng/dL is equivocal

When the laboratory value obtained falls into the equivocal range, using an FT level is recommended to differentiate eugonadism from hypogonadism. A primary recommendation from the Endocrine Society is to standardize testosterone assays so that normal values for TT and FT can be established.

In summary, practicing physicians should measure T levels only in men with signs and symptoms of hypogonadism. The initial diagnostic test should be a TT level by a reliable assay such as liquid chromatography-mass spectrometry/mass spectrometry, preferably in the morning. The T level ranges specific to that assay should be used to interpret the patient’s levels.

 

References

  1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006;91:1995-2010.
  2. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007;92:405-413.
  3. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666-3672.

 

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