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Testosterone Testing

Test code(s) 873, 14966, 15983, 30741, 36170

This is an outdated version of this FAQ. It was effective 07/08/2015 to 07/21/2015.

The current version is available here.



Overview of Age-related Low Testosterone

Question 1. What is hypogonadism?

Question 2. How is hypogonadism diagnosed?

Question 3. What are the different types of hypogonadism and the associated medical conditions?

Question 4. How common is hypogonadism?


Overview of Age-related Low Testosterone

By the time men reach the age of 40, their testosterone levels have begun a slow decline, dropping an estimated 1% to 2% each year. The rate of decline is not constant across study populations nor among individual men. In one study, as many as half of men in their 80s have low levels of testosterone (<325 ng/dL).1 Other studies have observed lower prevalence. For example, the Hypogonadism in Males (HIM) study estimated prevalence to be 39% among men ≥45 years of age (mean 61.6, standard deviation 10.6). Two thirds of those with low testosterone (<300 ng/dL) presented with one or more symptoms of hypogonadism.2

Low testosterone, or hypogonadism, has been associated with reduced sexual desire, erectile dysfunction, change in sleep patterns, depression and fatigue, and physical changes such as increased body fat, reduced muscle mass, diabetes, low bone density, and hypertension. Low levels, however, don’t always lead to symptoms. Thus, men aren’t typically tested for low testosterone unless they are experiencing symptoms such as erectile dysfunction, difficulty achieving an orgasm, less-intense orgasm, or low libido. The more symptoms a man has, the more likely he is to have low testosterone.

Tests for free, bioavailable, and total testosterone can help diagnose hypogonadism and rule out other conditions,    such as cardiovascular disease, that may manifest similar symptoms. Due to circadian rhythm, specimens should be collected between 7 and 10 a.m. Testing of 2 specimens may be preferable before diagnosing hypogonadism because of day-to-day fluctuations. Quest Diagnostics uses both immunoassay and LC/MS/MS technologies for testosterone testing. Unlike direct immunoassays (ie, those with no extraction or chromatography), LC/MS/MS technology can accurately measure the low levels observed in men with hypogonadism. LC/MS/MS meets the Endocrine Society’s recommendations for testosterone testing.3

Testosterone treatment, often delivered through gel or patch, may be considered if patients have low testosterone and symptoms related to the reduced hormone. The U.S. Food and Drug Administration (FDA) has approved testosterone therapy only for the treatment of low testosterone due to a diagnosed medical condition

such as a failure to produce testosterone. Before treating with testosterone, however, consider the benefits, risks, and other causes of low testosterone. Other causes include injury to the testicles, testicular cancer or treatment for testicular cancer, hormonal disorders, HIV or other infection, chronic liver or kidney disease, type 2 diabetes, and obesity. Sleep disorders such as sleep apnea can also cause low testosterone, since testosterone is at its highest level during deep REM sleep.

The primary risks of testosterone therapy include increased growth of the prostate, increased risk of prostate cancer, increase in breast size, sleep disturbance, and an increase in red blood cells, which may lead to an increased risk of heart disease. Thus, men with prostate or breast cancer, or those at high risk of these diseases, are typically not treated with testosterone. Those taking testosterone may be monitored using total testosterone, hematocrit, and bone density and prostate cancer screenings.

Studies published in the last few years have raised concerns regarding testosterone therapy and increased cardiovascular risk. So far, these studies are inconclusive. In high doses, androgens tend to raise LDL cholesterol levels and lower HDL cholesterol levels. But this effect varies depending on the clinical situation. For example, men who receive androgen-deprivation therapy for prostate cancer have essentially no or extremely low testosterone levels, but their cholesterol levels typically rise. A U.S. Veterans Affairs study published in 2013 showed a 30% increase in myocardial infarction, stroke, and death among men on testosterone therapy.4 In January 2014, a study of 55,593 men found the likelihood of myocardial infarction doubled within 90 days of starting testosterone therapy among men 65 years and older. The risk was almost three-fold in younger men with pre-existing heart disease.5 Other studies have shown a lower risk of all-cause mortality.6 Given the uncertainty, the Endocrine Society has recommended that until evidence from large clinical trials is available, “patients should be made aware of the potential risk of cardiovascular events in middle-aged and older men.”7 The Society recommends physicians discuss the risks and benefits of using testosterone, especially with patients who have pre-existing heart disease.

In summary, testosterone is a vital hormone, and low levels are associated with a spectrum of symptoms closely associated with aging. Hypogonadism diagnoses require clinical assessment and laboratory testing. The current approach to supplementation needs to be reassessed given emerging data on benefits and risks. Both clinical assessment and laboratory testing serve to monitor therapeutic response and identify potential adverse effects.


  1. Harman SM, et al. Baltimore longitudinal study of aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab. 2001;86:724.
  2. Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60:762-769.
  3. Rosner W, Auchus RJ, Azziz R, et al. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society Position Statement. J Clin Endocrinol Metab. 2007;92:405-413.
  4. Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829-1836.  
  5. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9:e85805.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085805.
  6. Shores MM, Smith NL, Forsberg CW, et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab. 2012;97:2050-2058.
  7. Endocrine Society. The risk of cardiovascular events in men receiving testosterone therapy. An Endocrine Society Statement.https://www.endocrine.org/~/media/endosociety/Files/Advocacy%20and%20Outreach/Position%20Statements/Other%20Statements/The%20Risk%20of%20Cardiovascular%20Events%20in%20Men%20Receiving%20Testosterone%20Therapy.pdf. Published February 7, 2014. Accessed April 16, 2015.


Question 1. What is hypogonadism?

The Endocrine Society defines male hypogonadism as “a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and a normal number of spermatozoa due to disruption of one or more levels of the hypothalamic-pituitary-testicular (HPT) axis.”1

Many men have total testosterone levels below the lower limit of the reference range with no clinical symptoms. Other men have symptoms with total testosterone levels above the lower limit of the reference range. Men may develop different symptoms at different ages, and the sequence of symptom presentation may also vary. Thus, there is no single clinical presentation that fits all men.

Various symptoms of hypogonadism are also observed in other medical conditions. For example, fatigue may be due to diabetes, iron deficiency, depression, or hyperthyroidism. Bone loss may be secondary to vitamin D deficiency. These alternative medical conditions may be underdiagnosed and undertreated.

With aging, the responsiveness to pituitary hormones declines. The number of Leydig cells in the testes decline in number and sensitization. Luteinizing hormone levels become more erratic and affect the availability of testosterone. Growth hormone and dehydroepiandrosterone (DHEA) levels decline with aging, contributing to declines in muscle mass, strength, and overall well-being.

Total testosterone levels decrease by approximately one-third between ages 20-30 years and age 75 years.2 The onset of decline is insidious, and the decline is gradual. In contrast, free testosterone declines by approximately 60% in the same time span.2 Other hormone levels drop as well. The interaction among these hormones may affect their actions and the development of symptoms.

Question 2. How is hypogonadism diagnosed?

Hypogonadism is diagnosed based on clinical symptoms and testosterone measurements. One common approach to evaluating symptoms is use of a questionnaire such as the Androgen Deficiency in Aging Men (ADAM) questionnaire.3,4 This questionnaire has a reported sensitivity of 88% and specificity of 60%.4 Thus, eight of nine men with hypogonadism will be identified with ADAM. However, four of ten men will be falsely identified as having hypogonadism. If the hypogonadism prevalence is 10%, then 20% of those positively identified by ADAM will really have hypogonadism (true positives). On the other hand, 98% of those who are negative by ADAM will not have hypogonadism (true negatives).

The components of the ADAM questionnaire include:

  • Changes in mood (fatigue, depression, anger)
  • Decreased body hair (feminization)
  • Decreased bone mineral density and possible resulting osteoporosis
  • Decreased lean body mass and muscle strength
  • Decreased libido and erectile quality
  • Increased visceral fat
  • Oligospermia or azoospermia

There is no consensus on the degree of these signs or symptoms required for diagnosis.

An alternative questionnaire is the Massachusetts Male Aging Survey (MMAS) questionnaire.5 This survey has far better sensitivity than specificity.

Scores derived from these questionnaires do not predict or correlate well with measured total testosterone.6 Specimens for testosterone measurement should be collected between 7 and 10 a.m., because levels show a circadian rhythm; peak levels occur in the morning, especially among younger men. Also, because levels can fluctuate day-to-day, repeat testing is recommended by the Endocrine Society prior to the initiation of treatment.1

Free and bioavailable testosterone measurements may be helpful when the total testosterone concentration is near the decision level or when perturbations in sex hormone binding globulin (SHBG) are likely. Longitudinal studies such as the Massachusetts Male Aging Study suggest that total testosterone decreases at a rate of about

1.6% annually, with a concomitant 1.3% annual increase in SHBG after age 40 years.7 An estimated 30% of men aged 70–79 years have low serum total testosterone, and approximately 70% have low bioavailable testosterone levels.2 Free and bioavailable testosterone can be measured or calculated based on the total testosterone, SHBG, and albumin concentrations.

Luteinizing hormone (LH) testing may be useful in determining if a patient’s hypogonadism is primary (elevated LH) or secondary (LH within range or low). Prolactin testing is used to rule out hyperprolactinemia.

Question 3. What are the different types of hypogonadism and the associated medical conditions?

There are 3 types of male hypogonadism: primary, secondary, or mixed. All 3 are characterized by deficiency of both testosterone and spermatozoa. In primary hypogonadism, testicular dysfunction leads to low levels of testosterone and high levels of LH and follicle stimulating hormone (FSH).1 In secondary hypogonadism, dysfunction of the hypothalamic-pituitary axis results in low levels of testosterone, LH, and FSH.1 Mixed hypogonadism manifests a mixture of primary and secondary hypogonadism.1 It can be observed in older men.

In contrast, the European Male Aging Study (EMAS) defined testosterone deficiency as primary (low total testosterone with decreased LH), secondary (low total testosterone with elevated LH), or compensated (within range total testosterone with elevated LH).8 The prevalence of each among 3369 community-dwelling men ages 40-79 years was:

  • Primary hypogonadism:            11.8%
  • Secondary hypogonadism:        2.0%
  • Compensated hypogonadism:    9.5%

The DETECT Study found low total testosterone (<300 ng/dL) was associated with obesity, metabolic syndrome, and ≥ 6 prescription medications. Very low levels of total testosterone (<100 ng/dL) were associated with advanced age, cancer, and liver disease.9

The HIM Study found the following clinical associations, reported as odds radio (with 95% confidence intervals).10 All were statistically significant.

  • Obesity                         2.38 (1.93-2.93)
  • Diabetes                       2.09 (1.70-2.58)
  • Hypertension                 1.84 (1.53-2.22)
  • Dyslipidemia                 1.47 (1.23-1.76)
  • Asthma/COPD              1.40 (1.04-1.86)
  • Prostatic disease          1.29 (1.03-1.62)

Question 4. How common is hypogonadism and low testosterone?

Araujo et al determined the prevalence of hypogonadism based on ≥3 related symptoms plus testosterone concentrations in a study of 1691 men aged 40-70 years. The overall prevalence was 6.0%.11 The prevalence was 4.1%, 4.5%, and 9.4% in men 40-49 years, 50-59 years, and 60-70 years, respectively.11

The Baltimore Longitudinal Study of Aging used a criterion of <325 ng/dL to define low testosterone; presence or absence of symptoms was not determined For men in their 60s, 70s, and 80s, the percent of men with low testosterone was approximately 20%, 30%, and 50%, respectively.2

  1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2010;95:2536-2559.
  2. Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724-731.
  3. Moore C, Huebler D, Zimmermann T, et al. The Aging Males’ Symptoms scale (AMS) as outcome measure for treatment of androgen deficiency. Eur Urol. 2004;46:80-87.
  4. Morley JE, Charlton E, Patrick P, et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism. 2000;49:1239-1242.
  5. Smith KW, Feldman HA, McKinlay JB. Construction and field validation of a self-administered screener for testosterone deficiency (hypogonadism) in ageing men. Clin Endocrinol (Oxf). 2000;53:703-711.
  6. Morley JE, Perry HM 3r d, Kevorkian RT, et al. Comparison of screening questionnaires for the diagnosis of hypogonadism. Maturitas. 2006;53:424-429.
  7. Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002;87:589-598.
  8. Tajar A, Forti G, O’Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95:1810-1818.
  9. Schneider HJ, Sievers C, Klotsche J, et al. Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study. Clin Endocrinol (Oxf). 2009;70:446-454.
  10. Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60:762-769.
  11. Araujo AB, O’Donnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004;89:5920-5926.
This FAQ is provided for informational purposes only and is not intended as medical advice. A clinician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
Document FAQS.165 Version: 0
Version 0 effective 07/08/2015 to 07/21/2015