Estradiol in Men: What is the Most Accurate Blood Test?

Recent studies show the importance of estradiol in men and how low estradiol can be detrimental for not only for bone but also for sex drive. Low estradiol has also been linked to fat gain. So, physicians should be careful about treating men who are obviously being over diagnosed with high estradiol due to the use of the wrong test. This study compares the old estradiol blood test assay (ECLIA) to the more accurate sensitive one (LC/MS/MS).

The sensitive estradiol test is a method for measuring estradiol levels in men (and children) using a sensitive liquid chromatography-tandem mass spectrometry (LC/MS)-based assay[2]. It is considered more accurate for men because it provides better sensitivity and accuracy at lower estradiol concentrations, which are typically found in men, as opposed to higher concentrations found in adult females[1][2].

Immunoassay-based estradiol tests, on the other hand, perform best at higher concentrations of estradiol, making them more suitable for individuals with levels in the adult-female range[2]. The sensitive estradiol test, with its greater sensitivity at lower levels, is more appropriate for men who generally have lower levels of estradiol compared to adult females[3].

Comparisons of Immunoassay and Mass Spectrometry Measurements of Serum Estradiol Levels and Their Influence on Clinical Association Studies in Men

 (Source: The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 6, 1 June 2013, Pages E1097–E110)


Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations, when compared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men.


Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes.

Design and Setting:

Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included.

Main Outcome Measures:

Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index.


Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53–0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP (C Reactive Protein- An Inflammatory marker).


Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes.