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Doyle
Straseski
Male hypogonadism is defined as a failure, in individuals with testes, to produce either a normal concentration of testosterone or a normal number of spermatozoa. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020;8(5):970-987.
A diagnosis of hypogonadism requires both clinical signs or symptoms of testosterone deficiency and consistently low testosterone concentrations, as demonstrated by laboratory testing. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020;8(5):970-987. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432.
Quick Answers for Clinicians
Compared with primary hypogonadism, functional hypogonadism is associated with a later age of onset, more modest decreases in testosterone concentrations, and subtler clinical presentations. 4 Marcelli M, Mediwala SN. Male hypogonadism: a review. J Investig Med. 2020;68(2):335-356. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Research indicates that there has been an increase in testosterone prescriptions in the United States and that many adult cisgender males who are prescribed testosterone therapy do not have their testosterone concentrations checked or do not meet the criteria to be diagnosed with testosterone deficiency. 3 Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020;8(5):970-987. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432.
No, general population screening for male hypogonadism is not recommended. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Reference intervals for testosterone assays vary widely between laboratories and methods. Standardization is important because it improves the accuracy and precision of laboratory testing for the diagnosis of diseases such as male hypogonadism. The CDC provides an accuracy-based standardization program for some hormone testing, which includes total testosterone. 5 Centers for Disease Control and Prevention. Steroid hormones standardization programs. Last reviewed Mar 2023; accessed Mar 2023. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Centers for Disease Control and Prevention. Steroid hormones standardization programs. Last reviewed Mar 2023; accessed Mar 2023.
Free testosterone assays are not included in the CDC’s standardization program. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
For guidance in selecting an appropriate ARUP test, please refer to the Testosterone Tests Comparison table.
Indications for Testing
Testing for hypogonadism should be performed in individuals with testes who present with signs and symptoms of testosterone deficiency or who have conditions associated with testosterone deficiency (eg, infertility, pituitary mass, use of opioids or glucocorticoids, and withdrawal from anabolic-androgenic steroids). 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Highly specific signs and symptoms include incomplete or delayed sexual development, loss of body hair, and testicular volume <6 mL. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
For individuals primarily concerned with infertility, refer to the ARUP Consult Infertility topic.
Laboratory Testing
Diagnosis
The diagnosis of hypogonadism is established by laboratory confirmation of low testosterone in patients with signs and symptoms suggestive of hypogonadism. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Testosterone
Total testosterone is the initial test for hypogonadism in individuals with testes. The preferred testing method is immunoassay for adult cisgender males and mass spectrometry for prepubertal individuals 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432.
Free testosterone should be assessed in individuals who have a borderline total testosterone concentration (a concentration near the lower limit of the reference interval) or who have protein-binding abnormalities (conditions that either increase or decrease sex hormone-binding globulin [SHBG] activity). 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
For more information about which testosterone test is appropriate for a particular patient population, see the Testosterone Tests Comparison table.
If low testosterone is confirmed in patients with signs and symptoms suggestive of hypogonadism, then a diagnosis of hypogonadism is established. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Luteinizing Hormone and Follicle-Stimulating Hormone
Assessing the concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) can help differentiate between a diagnosis of primary hypogonadism and secondary hypogonadism. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Etiologic Testing
For individuals with primary hypogonadism, consider karyotype testing to assess for Klinefelter syndrome, especially for those with a testicular volume of <6 mL. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
For those with secondary hypogonadism, iron saturation and/or serum ferritin testing should be performed to assess for iron overload syndromes such as hemochromatosis, and serum prolactin should be measured to assess for hyperprolactinemia. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Treatment-Related Testing
Testosterone
Testosterone concentration should be assessed 3-6 months after the initiation of therapy, then again at 12 months after the initiation of therapy, and then annually thereafter with the goal of achieving a concentration in the middle of the reference interval. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Testosterone Reference Intervals and Standardization
Reference intervals for testosterone assays vary widely between laboratories and methods. The CDC provides an accuracy-based standardization program for total testosterone testing, and, ideally, testosterone testing should be conducted using a CDC-certified assay. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Centers for Disease Control and Prevention. Steroid hormones standardization programs. Last reviewed Mar 2023; accessed Mar 2023.
Free testosterone assays also lack standardization. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
The recommended testosterone concentrations for diagnosis of hypogonadism and therapeutic goals of testosterone therapy vary by society guideline. The concentrations as recommended by several different societies are listed below.
Society | Cutoff for Low Total Testosterone | Borderline Total Testosterone Concentrationsa | Target Interval for Testosterone Therapy |
---|---|---|---|
Endocrine Society (2018) | <264 ng/dL <9.2 nmol/L | 200-400 ng/dL 6.9-13.9 nmol/L | 350-600 ng/dL 14.1-24.5 nmol/L |
American Urological Association (2018) | <300 ng/dL <10.4 nmol/L | n/a | 450-600 ng/dL 15.6-20.8 nmol/L |
European Association of Urology (2018) | <231 ng/dL <8 nmol/L | 231-346 ng/dL 8-12 nmol/L | Midnormalb |
International Society for Sexual Medicine (2015) | <231 ng/dL <8 nmol/L | 231-346 ng/dL 8-12 nmol/L | Midnormalb |
British Society for Sexual Medicine (2017) | <231 ng/dL <8 nmol/L | 231-346 ng/dL 8-12 nmol/L | 433-865 ng/dL 15-30 nmol/L |
aFollow-up testing with free testosterone is recommended. bNo numerical interval offered. n/a, not available Source: Bhasin, 2018 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. Kwong JCC, Krakowsky Y, Grober E. Testosterone deficiency: a review and comparison of current guidelines. J Sex Med. 2019;16(6):812-820. Dohle GR, Arver S, Bettocchi C, et al. Guidelines on male hypogonadism. European Association of Urology. [Published: 2018; Accessed: Feb 2022] Dean JD, McMahon CG, Guay AT, et al. The International Society for Sexual Medicine's process of care for the assessment and management of testosterone deficiency in adult men. J Sex Med. 2015;12(8):1660-1686. Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine guidelines on adult testosterone deficiency, with statements for UK practice. J Sex Med. 2017;14(12):1504-1523. |
Hemoglobin and Hematocrit
Because testosterone therapy may increase the risk of polycythemia, hemoglobin and hematocrit should be assessed before initiating therapy. 3 Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Prostate-Specific Antigen
Individuals 55-69 years of age (or 40-69 years of age in high-risk groups) who are pursuing testosterone therapy should participate in shared decision-making to determine if monitoring for prostate cancer is appropriate. 1 Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
Estradiol
Serum estradiol should be measured in individuals with gynecomastia before beginning testosterone therapy. 3 Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432.
ARUP Laboratory Tests
Quantitative Electrochemiluminescent Immunoassay
Quantitative Electrochemiluminescent Immunoassay/Calculation
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry/Electrochemiluminescent Immunoassay/Calculation
Quantitative Electrochemiluminescent Immunoassay
Giemsa Band
Quantitative Chemiluminescent Immunoassay
Quantitative Spectrophotometry
Quantitative Chemiluminescent Immunoassay
References
-
29562364
Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
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32026626
Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020;8(5):970-987.
-
29601923
Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432.
-
31988219
Marcelli M, Mediwala SN. Male hypogonadism: a review. J Investig Med. 2020;68(2):335-356.
-
CDC - HoST-VDSCP-certified participants
Centers for Disease Control and Prevention. Steroid hormones standardization programs. Last reviewed Mar 2023; accessed Mar 2023.
-
31080101
Kwong JCC, Krakowsky Y, Grober E. Testosterone deficiency: a review and comparison of current guidelines. J Sex Med. 2019;16(6):812-820.
-
EAU - Guidelines on male hypogonadism
Dohle GR, Arver S, Bettocchi C, et al. Guidelines on male hypogonadism. European Association of Urology. [Published: 2018; Accessed: Feb 2022]
-
26081680
Dean JD, McMahon CG, Guay AT, et al. The International Society for Sexual Medicine's process of care for the assessment and management of testosterone deficiency in adult men. J Sex Med. 2015;12(8):1660-1686.
-
29198507
Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine guidelines on adult testosterone deficiency, with statements for UK practice. J Sex Med. 2017;14(12):1504-1523.
For a comparison of ARUP testosterone tests, refer to the Testosterone Tests Comparison table.