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

Identification of late-onset hypogonadism in middle-aged and elderly men

N Engl J Med. 2010;363(2):123-35

Introduction:  Researchers want evidence-based criteria for diagnosing late-onset hypogonadism in the general population based on an association between a low testosterone level and symptoms.  This is desired because the association between aging-related testosterone deficiency and late-onset hypogonadism in men is controversial.

Methods:  There were 3,369 men (age range: 40-79 years) who were included in the study; they came from 8 European centers.  One-hundred-fifty were excluded because of known testicular or pituitary diseases or current use of medications that could impact testicular or pituitary function, or sex-steroid clearance.

Questionnaires were used to collect data related to general, sexual, physical, and psychological health in the subjects.

Morning blood samples were used to measure total testosterone levels by mass spectrometry.  SHBG levels were assayed by platform immunoassay. Vermeulen’s formula was used to calculate free testosterone levels.

The data were randomized into training and validation sets to be used for confirmatory analyses.

Results:  The training set had several symptoms significantly related to testosterone levels.  Those symptoms were: poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue.

An increase in the probabilities of the 3 sexual symptoms (poor morning erection, low sexual desire, erectile dysfunction) and limited vigorous physical activity was seen with decreased testosterone levels (ranges, total testosterone:  8.0-13.0 nmol/L; free testosterone: 150-280 pmol/L).

The 3 sexual symptoms had a syndromic association with decreased testosterone levels.  Additionally, there was an inverse relationship seen between increasing number of sexual symptoms and decreasing testosterone level.

The validation set independently confirmed these relationships, and the strengths of the association between low testosterone levels and symptoms aided in identifying the minimum criteria for late-onset hypogonadism.

Conclusions:  Late-onset hypogonadism can be identified when there are at least 3 sexual symptoms present, as well as a total testosterone level < 11 nmol/L and a free testosterone level < 220 pmol/L.


This article seeks to correlate symptoms with low T and to create diagnostic criteria for late-onset hypogonadism.

It is well known that there is an age-related decline in testosterone levels; however, defining which men have late-onset hypogonadism remains controversial. Symptoms associated with low testosterone in aging men are often non-specific and overlap with symptoms found in other common illnesses. Moreover, the testosterone level(s) below which symptoms arise is unclear. There are reports that threshold levels vary depending upon the symptom.

The purpose of this study was to identify the threshold level(s) for testosterone below which symptoms emerge in aging men in order to create diagnostic criteria for late-onset hypogonadism. It was noted that the presence of at least three sexual symptoms in addition to a total testosterone level <11nmol/L and free testosterone <220pmol/L supports a diagnosis of hypogonadism in the aging male.

Using these criteria, it was noted that the prevalence of late-onset hypogonadism was 2.1%, significantly lower than the prevalence of low testosterone in this population. It is, therefore, very important to include the presence of symptoms in evaluation, to avoid over diagnosis.

Future interventional studies using these criteria to initiate testosterone therapy are required to assess the risks and benefits of treating this population.

Next Article:
Reference ranges of testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts
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