Free Estradiol (f E2)

Clinical Significance:
Estradiol is one of the three main Estrogens derived from metabolism of Testosterone and also converted reversibly to Estrone.  Estradiol is produced by ovarian follicles.  Estradiol is the most biologically potent of the Estrogens.  Estradiol is excreted into the urine in several different conjugated forms and also as unconjugated Estradiol. Estradiol is bound strongly to Estrogen Binding Globulin but is also present in the “free” (unbound) form or loosely bound to Albumin.   Only Estradiol in the “Free” form has biological activity.  Factors that influence Estrogen Binding Globulin have a dramatic effect on “Free” Estradiol levels.  Patients on Estrogen Replacement therapy may have greatly elevated Estrogen Binding Globulin levels leading to very high total Estradiol levels but without the correlating elevation in “Free” Estradiol levels and Estrogenic activity.  Thyroid medication, contraceptives and Estrogens decrease the percent of “Free” Estradiol shielding the true Estrogenic level of activity from total Estradiol determinations.

Reference Ranges:
Male:                                   0.10 – 0.98 pg/ml
Female:
  Follicular:                           0.34 – 1.26 pg/ml
  Luteal:                                0.80 – 3.45 pg/ml
  Menopausal:                      0.12 – 0.39 pg/ml

Procedure:
“Free” Estradiol is measured by a radioimmunodisplacement assay and a radioimmunoassay following extraction of specimens.

Patient requirements:
Patient should not be on any Steroid, ACTH, Gonadotropin or Estrogen medications, if possible, for at least 48 hours prior to collection of specimen.  Oral contraceptives and estrogen replacement therapy may influence “Free” Estradiol levels.

Specimen Collection:
3 ml serum or EDTA plasma should be collected and separated as soon as possible.  Minimum specimen size is 1.5 ml.

Shipping Instructions:
Ship specimens at room temperature or frozen in dry ice.

References:
1. N Mounib, Ch Sultan, J Bringer, B Hedon, JC Nicolas, P Cristol, N Bressot, and B Descomps.  Correlations between Free Plasma Estradiol and Estrogens Determined by Bioluminescence in Saliva, Plasma, and Urine during Spontaneous and FSH Stimulated Cycles in Women.  Journal of Steroid Biochemistry 31: 861-865, 1988.
 
2. MJ Reed, RW Cheng, CT Noel, HAF Dudley, and VHT James.  Plasma Levels of Estrone, Estrone Sulfate, and Estradiol and the Percentage of Unbound Estradiol in Postmenopausal Women with and without Breast Disease.  Cancer Research 43: 3940-3943, 1983.