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Test Code ESTRG Estrogens, Estrone (E1) and Estradiol (E2), Fractionated, Serum

Reporting Name

Estrogens, E1+E2, fractionated, S

Useful For

Simultaneous high-sensitivity determination of serum estrone and estradiol levels

 

Situations requiring either higher sensitivity estradiol measurement, estrone measurement, or both, including

-As part of the diagnosis and workup of precocious and delayed puberty in females and, to a lesser degree, males

-As part of the diagnosis and workup of suspected disorders of sex steroid metabolism, eg, aromatase deficiency and 17 alpha-hydroxylase deficiency

-As an adjunct to clinical assessment, imaging studies, and bone mineral density measurement in the fracture risk assessment of postmenopausal women and, to a lesser degree, older men

-Monitoring low-dose female hormone replacement therapy in postmenopausal women

-Monitoring antiestrogen therapy (eg, aromatase inhibitor therapy)

 

Applications that require moderately sensitive measurement of estradiol including:

-Evaluation of hypogonadism and oligo-amenorrhea in females

-Assessing ovarian status, including follicle development, for assisted reproduction protocols (eg, in vitro fertilization)

 

In conjunction with luteinizing hormone measurements, monitoring of estrogen replacement therapy in hypogonadal premenopausal women

 

Evaluation of feminization, including gynecomastia, in males

 

Diagnosis of estrogen-producing neoplasms in males, and, to a lesser degree, females

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Serum Red


Specimen Required


Collection Container/Tube: Red top (Serum gel/SST is not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 1.2 mL

Collection Instructions: Centrifuge and aliquot serum in plastic vial within 2 hours of collection.


Specimen Minimum Volume

0.8 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Refrigerated (preferred) 28 days
  Ambient  28 days
  Frozen  28 days

Reference Values

ESTRONE (E1)

CHILDREN*

1-14 days: Estrone levels in newborns are very elevated at birth but will fall to prepubertal levels within a few days.

Males

Tanner stages#

Mean age

Reference range

Stage I (>14 days and prepubertal)

7.1 years

Undetectable-16 pg/mL

Stage II

11.5 years

Undetectable-22 pg/mL

Stage III

13.6 years

10-25 pg/mL

Stage IV

15.1 years

10-46 pg/mL

Stage V

18 years

10-60 pg/mL

#Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for boys at a median age of 11.5 (± 2) years. For boys there is no proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage V (adult) should be reached by age 18.

Females

Tanner stages#

Mean age

Reference range

Stage I (>14 days and prepubertal)

7.1 years

Undetectable-29 pg/mL

Stage II

10.5 years

10-33 pg/mL

Stage III

11.6 years

15-43 pg/mL

Stage IV

12.3 years

16-77 pg/mL

Stage V

14.5 years

17-200 pg/mL

#Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for girls at a median age of 10.5 (± 2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African American girls. Progression through Tanner stages is variable. Tanner stage V (adult) should be reached by age 18.

*The reference ranges for children are based on the published literature,(1,2) cross-correlation of our assay with assays used to generate the literature data and on our data for young adults.

ADULTS

Males: 10-60 pg/mL

Females

Premenopausal: 17-200 pg/mL

Postmenopausal: 7-40 pg/mL

Conversion factor

E1: pg/mL x 3.704=pmol/L (molecular weight=270)

 

ESTRADIOL (E2)

CHILDREN*

1-14 days: Estradiol levels in newborns are very elevated at birth but will fall to prepubertal levels within a few days.

Males

Tanner stages#

Mean age

Reference range

Stage I (>14 days and prepubertal)

7.1 years

Undetectable-13 pg/mL

Stage II

12.1 years

Undetectable-16 pg/mL

Stage III

13.6 years

Undetectable-26 pg/mL

Stage IV

15.1 years

Undetectable-38 pg/mL

Stage V

18 years

10-40 pg/mL

#Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for boys at a median age of 11.5 (± 2) years. For boys there is no proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage V (adult) should be reached by age 18.

Females

Tanner stages#

Mean age

Reference range

Stage I (>14 days and prepubertal)

7.1 years

Undetectable-20 pg/mL

Stage II

10.5 years

Undetectable-24 pg/mL

Stage III

11.6 years

Undetectable-60 pg/mL

Stage IV

12.3 years

15-85 pg/mL

Stage V

14.5 years

15-350 pg/mL**

#Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for girls at a median age of 10.5 (± 2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African American girls. Progression through Tanner stages is variable. Tanner stage V (adult) should be reached by age 18.

*The reference ranges for children are based on the published literature,(1,2) cross-correlation of our assay with assays used to generate the literature data and on our data for young adults.

ADULTS

Males: 10-40 pg/mL

Females

Premenopausal: 15-350 pg/mL**

Postmenopausal: <10 pg/mL

**E2 levels vary widely through the menstrual cycle.

Conversion factor

E2: pg/mL x 3.676=pmol/L (molecular weight=272)

 

For SI unit Reference Values, see https://www.mayocliniclabs.com/order-tests/si-unit-conversion.html

Day(s) and Time(s) Performed

Monday through Friday

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

82670-Estradiol

82679-Estrone

 

When performed together as test ESTF:

82671 Estrogens, fractionated

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ESTF Estrogens, E1+E2, fractionated, S 53766-2

 

Result ID Test Result Name Result LOINC Value
81418 Estrone, S 2258-2
81816 Estradiol, Mass Spectrometry, S 2243-4

Clinical Reference

1. Elmlinger MW, Kuhnel W, Ranke MB: Reference ranges for serum concentrations of lutropin (LH), follitropin (FSH), estradiol (E2), prolactin, progesterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin in neonates, children and young adults. Clin Chem Lab Med. 2002;40(11):1151-1160

2. Cummings SR, Browner WS, Bauer D, Stone K, Ensrud K, Jamal S, Ettinger B: Endogenous hormones and the risk of hip and vertebral fractures among older women. N Engl J Med. 1998;339:733-738

3. Lughetti L, Predieri B, Ferrari M, et al: Diagnosis of central precocious puberty: endocrine assessment. J Pediatr Endocrinol Metab. 2000;13 Suppl 1:709-715

4. Ismail AA, Barth JH: Endocrinology of gynaecomastia. Ann Clin Biochem. 2001;38:596-607

5. Kligman I, Rosenwaks Z: Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders. Fertil Steril. 2001;76:1185-1190

6. Traggiai C, Stanhope R: Delayed puberty. Best Pract Res Clin Endocrinol Metab. 2002;16:139-151

7. Mauras N, Ross JL, Gagliardi P, et al: Randomized trial of aromatase inhibitors, growth hormone, or combination in pubertal boys with idiopathic short stature. J Clin Endocrinol Metab. 2016 Dec;101(12):4984-4993. doi: 10.1210/jc.2016-2891

8. Ketha H, Girtman A, Singh RJ: Estradiol assays-The path ahead. Steroids. 2015 Jul;99(Pt A):39-44. doi: 10.1016/j.steroids.2014.08.009

9. Ingle JN, Cairns J, Suman VJ, et al: Anastrozole has an assocaition between degree of estrogen suppression and outcomes in early breast cancer and is a ligamd for estrogen receptor alpha. Clin Cancer Res. 2020 Jun 15;26(12):2986-2996 doi: 10.1158/1078-0432.CCR-19-3091

10. Richardson H, Ho V, Pasquet R, et al: Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial. Menopause. 2020 Jun;27(6):693-700 doi: 10.1097/GME.0000000000001568.

Method Description

Estrogens are fractionated into estradiol and estrone by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The LC-MS/MS method employs an organic extraction to remove water-soluble conjugates and to allow for concentration of the specimen. The method is free from interference and represents a reference methodology.

 

17 Beta-estradiol and estrone are extracted from 0.5 mL of serum with the organic solvent methylene chloride. Deuterated 17 beta-estradiol-d5 and estrone-d4 are added to each specimen before the liquid extraction and serve as internal standards. After derivatization with dansyl chloride, HPLC is used prior to introduction of the derivatized sample extract into the MS/MS.(Bidlingmaier F, Wagner-Barnack M, Butenandt O, Knorr D: Plasma estrogens in childhood and puberty under physiologic and pathologic conditions. Pediatr Res. 1973;7(11):901-907)

 

The calibration utilizes an 8-point standard curve over a concentration range of 0 to 600 pg/mL.(Anari MR, Bakhtiar R, Zhu B, et al: Derivatization of ethynylestradiol with dansyl chloride to enhance electrospray ionization: application in trace analysis of ethynylestradiol in Rhesus monkey plasma. Anal Chem. 2002;74,4136-4144)

Analytic Time

2 days

Reject Due To

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Profile Information

Test ID Reporting Name Available Separately Always Performed
E1 Estrone, S Yes Yes
EEST Estradiol, Mass Spectrometry, S Yes Yes

Secondary ID

84230