Estradiol in Men: Optimal Testing Recommendations
- Measurement of estradiol in men (and children) should be performed by a sensitive liquid chromatography-tandem mass spectrometry (LC/MS)-based assay.
- Immunoassay-based estradiol tests perform best at higher concentrations of estradiol and therefore work well for those with levels in the adult-female range.
Guidelines for Test Utilization
What does the test tell me?
This test, when measured by LC/MS, produces an accurate and sensitive quantitation of estradiol in circulation. If above the sex- and age-appropriate reference interval, this may be an indicator of a feminizing adrenal tumor. Estradiol values below the reference interval are consistent with deficiency from aromatase inhibitors, either congenital or acquired.
When should I order this test?
Estradiol by LC/MS in men should be used to evaluate men with symptoms of estradiol excess (primarily manifest as gynecomastia), steroid-secreting adrenal, hepatic, or testicular tumors or estradiol deficiency (decreased libido, low bone density, and increased body fat. Estradiol may also be followed in men receiving testosterone replacement therapy.
When should I NOT order this test?
Do not order estradiol or other estrogens by immunoassay on men, children, and postmenopausal women.
How should I interpret the result?
Estradiol in men should be interpreted in light of sex- and age-appropriate reference intervals. Values above or below the reference interval likely indicate estrogen excess or deficiency, respectively.
Is the test result diagnostic/confirmatory of the condition? If not, is there a diagnostic/confirmatory test?
Estradiol results alone are not particularly indicative of any specific disease or disorder. Additional testing is necessary to elucidate the cause of specific symptoms (see "What other tests might be indicated?").
Are there factors that can affect the lab result?
Immunoassay testing of estradiol is generally only appropriate for concentrations over around 50 pg/mL, otherwise immunoassays tend to overestimate the actual concentration. Therefore, individuals with low concentrations of estradiol should not have it measured by immunoassay. Groups with low estradiol levels include men, children, postmenopausal women, and women treated with aromatase inhibitors. Additionally, Fulvestrant, a selective estrogen receptor degrader class of drug, has been shown to cross react with estrogen immunoassays, and therefore those taking this drug should not have estrogen measured by immunoassay.
Are there considerations for special populations?
Children and post-menopausal women also have low circulating estradiol and therefore also require testing by LC/MS.
What other test(s) might be indicated?
Other tests to order depends upon the patient's symptoms: decreased libido may also necessitate total and possibly free testosterone, prolactin, follicle stimulating hormone (FSH), and luteinizing hormone (LH) testing. Low bone density may require imaging-based assessment, such as dual-energy x-ray absorptiometry (DEXA). Gynecomastia evaluation should include testing for other causes, including hypogonadism, cirrhosis, testicular tumors, or thyroid disease.
Ohlsson C, Nilsson ME, Tivesten A, et al. Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men. J Clin Endocrinol Metab. 2013;98(6):E1097-1102.
Finkelstein JS, Lee H, Burnett-Bowie S-AM, et al. Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men. New England Journal of Medicine. 2013;369(11):1011- 1022.
Leder BZ, LeBlanc KM, Schoenfeld DA, Eastell R, Finkelstein JS. Differential effects of androgens and estrogens on bone turnover in normal men. J Clin Endocrinol Metab. 2003;88(1):204-210.
Handelsman DJ, Newman JD, Jimenez M, McLachlan R, Sartorius G, Jones GR. Performance of direct estradiol immunoassays with human male serum samples. Clin Chem. 2014;60(3):510- 517.
Jaque J, Macdonald H, Brueggmann D, et al. Deficiencies in immunoassay methods used to monitor serum Estradiol levels during aromatase inhibitor treatment in postmenopausal breast cancer patients. SpringerPlus. 2013;2(1):5. doi:10.1186/2193-1801-2-5.
Last reviewed: June 2020. The content for Optimal Testing: AACC's Guide to Lab Test Utilization has been developed and approved by the AACC Academy and AACC's Science and Practice Core Committee.
As the fields of laboratory medicine and diagnostic testing continue to grow at an incredible rate, the knowledge and expertise of clinical laboratory professionals is essential to ensure that patients received the highest quality and most useful laboratory tests. AACC's Academy and Science and Practice Core Committee have developed a test utilization resource focusing on commonly misused tests in hospitals and clinics. Improper test utilization can result in poor patient outcomes and waste in the healthcare system. This important resource geared toward medical professionals recommends better tests and diagnostic practices. Always consult your laboratory director to make sure these recommendations are appropriate for your patient population.