EVIDENCE-BASED ANSWER
Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended.
Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture (strength of all recommendations: C, consensus guidelines and disease-oriented evidence).
Clinical commentary
Diagnosis is often straightforward, but treatment…not so much
Pamela A. Williams, MD
Uniformed Services University of the Health Sciences, Bethesda, Md
The causes of low testosterone are diverse and vary across the life span (TABLE).1,2
Although screening tests are integral to the evaluation, a successful diagnostic approach must begin with a detailed history and physical exam. Clinical clues coupled with judiciously selected tests typically lead to a straightforward diagnosis.
The decision whether or not to treat a patient diagnosed with partial androgen deficiency of aging is often less clear, especially when clinical symptoms are minimal or absent. The benefits of testosterone replacement therapy are significant, but so are the potential risks. Shared decision making with the patient is key to this dilemma.
Evidence summary
Our search retrieved no randomized controlled clinical trials evaluating the screening tests required to work-up a male with low testosterone. We therefore examined 2 consensus guidelines, 9 review articles, and disease-oriented evidence. The recommendations discussed here are based primarily on consensus guidelines and disease-oriented evidence.
Hypogonadism increases with age
Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism.3 Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men.1,3 A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050.4
TABLE
Causes of hypogonadism
| CLASS | LOCATION | CAUSES |
|---|---|---|
| Primary (low testosterone, elevated FSH) | Testes | Congenital Biosynthesis and chromosomal disorders (rare) Klinefelter syndrome (most common, 1:500-1000 males) |
| Acquired Chemotherapeutic agents Autoimmune disorders Aging Drugs Toxins (eg, alcohol) Infection Trauma Radiation Idiopathic causes | ||
| Secondary (low testosterone, normal or low FSH) | Pituitary gland | Congenital Kallmann syndrome (1:10,000 male births) Idiopathic causes Abnormal structural hormone defects |
| Acquired Chronic disease Drugs (eg, chronic opioids) Infection (eg, HIV) Trauma Tumors Idiopathic causes | ||
| Age-related (low testosterone, normal or elevated FSH) | Testes/hypothalamus | |
| Aging (common; 1%-2% per year after 65 years of age, 30%-70% at 60-80 years of age) | ||
| FSH, follicle-stimulating hormone; HIV, human immunodeficiency virus. Sources: Darby E et al1 and Badar F et al.2 | ||
Serum testosterone: The first-choice test
Serum testosterone measurements are considered the initial test of choice be-cause they’re reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels.3,5
In some cases—including patients with obesity, type 2 diabetes, or hypothyroidism—the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL).6,7