Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women

Shuping Wang, Francoise Paris, Charles S. Sultan, Robert X.D. Song, Laurence Demers, Bhaskar Sundaram, James Settlage, Susan Ohorodnik, Richard J. Santen

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A recent analysis of data from nine studies provided convincing evidence that plasma estradiol measurements predict the risk of breast cancer in normal postmenopausal women. However, the median values detected by the various assays used in this study varied by 5-fold. These and other published data in normal postmenopausal women suggest that assays measuring low plasma estradiol concentrations suffer from problems of sensitivity, specificity, and precision. Availability of a practical, low-cost, specific, precise, and ultrasensitive estrogen assay might allow enhanced prediction of the risk of breast cancer and provide an objective means of selecting postmenopausal women for breast cancer prevention. A recombinant cell ultrasensitive bioassay (RCUB) for estrogen was recently validated for use in prepubertal children. We postulated that the RCUB might also prove useful for measurement of postmenopausal levels and designed the present study to examine this possibility. Thirty normal postmenopausal volunteers provided blood samples for measurement of estrogen by RCUB and, for comparison, by RIA. The estrogenic activity measured by RCUB [mean ± SD, 11.9 ± 10.9 pmol/liter (SI units, 3.23 ±2.96 pg/ml)] was significantly lower than estradiol levels measured by RIA [43.7 ± 44.0 pmol/liter (11.9 ± 12.0 pg/ml)] in our volunteer subjects (P < 0.00001). Nonetheless, plasma estradiol levels measured by bioassay were significantly correlated with the estrogenic activity measured by RIA (r = 0.84) and by gas chromatography/tandem mass spectrometry (r = 0.85). To obtain biological evidence of the validity of the RCUB, we related plasma estrogen levels to body weight and body mass index and found highly significant correlations (r = 0.54 and r = 0.53, respectively). Surprisingly, 28 of 30 postmenopausal women were found to have estrogen levels in the prepubertal range with the RCUB. The levels detected by RCUB were similar to those previously reported using an ultrasensitive but less practical yeast bioassay. These results provide validation for the RCUB in postmenopausal women and suggest that it might prove useful for selection of women for drug therapy to prevent breast cancer.

Original languageEnglish (US)
Pages (from-to)1407-1413
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number3
DOIs
StatePublished - Mar 1 2005

Fingerprint

Bioassay
Biological Assay
Estrogens
Estradiol
Breast Neoplasms
Plasmas
Assays
International System of Units
Drug therapy
Tandem Mass Spectrometry
Gas chromatography
Yeast
Gas Chromatography-Mass Spectrometry
Mass spectrometry
Volunteers
Healthy Volunteers
Body Mass Index
Blood
Yeasts
Body Weight

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Wang, S., Paris, F., Sultan, C. S., Song, R. X. D., Demers, L., Sundaram, B., ... Santen, R. J. (2005). Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women. Journal of Clinical Endocrinology and Metabolism, 90(3), 1407-1413. https://doi.org/10.1210/jc.2004-0766
Wang, Shuping ; Paris, Francoise ; Sultan, Charles S. ; Song, Robert X.D. ; Demers, Laurence ; Sundaram, Bhaskar ; Settlage, James ; Ohorodnik, Susan ; Santen, Richard J. / Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 3. pp. 1407-1413.
@article{35d2f5367b6a46c7862cd2ed4daa703e,
title = "Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women",
abstract = "A recent analysis of data from nine studies provided convincing evidence that plasma estradiol measurements predict the risk of breast cancer in normal postmenopausal women. However, the median values detected by the various assays used in this study varied by 5-fold. These and other published data in normal postmenopausal women suggest that assays measuring low plasma estradiol concentrations suffer from problems of sensitivity, specificity, and precision. Availability of a practical, low-cost, specific, precise, and ultrasensitive estrogen assay might allow enhanced prediction of the risk of breast cancer and provide an objective means of selecting postmenopausal women for breast cancer prevention. A recombinant cell ultrasensitive bioassay (RCUB) for estrogen was recently validated for use in prepubertal children. We postulated that the RCUB might also prove useful for measurement of postmenopausal levels and designed the present study to examine this possibility. Thirty normal postmenopausal volunteers provided blood samples for measurement of estrogen by RCUB and, for comparison, by RIA. The estrogenic activity measured by RCUB [mean ± SD, 11.9 ± 10.9 pmol/liter (SI units, 3.23 ±2.96 pg/ml)] was significantly lower than estradiol levels measured by RIA [43.7 ± 44.0 pmol/liter (11.9 ± 12.0 pg/ml)] in our volunteer subjects (P < 0.00001). Nonetheless, plasma estradiol levels measured by bioassay were significantly correlated with the estrogenic activity measured by RIA (r = 0.84) and by gas chromatography/tandem mass spectrometry (r = 0.85). To obtain biological evidence of the validity of the RCUB, we related plasma estrogen levels to body weight and body mass index and found highly significant correlations (r = 0.54 and r = 0.53, respectively). Surprisingly, 28 of 30 postmenopausal women were found to have estrogen levels in the prepubertal range with the RCUB. The levels detected by RCUB were similar to those previously reported using an ultrasensitive but less practical yeast bioassay. These results provide validation for the RCUB in postmenopausal women and suggest that it might prove useful for selection of women for drug therapy to prevent breast cancer.",
author = "Shuping Wang and Francoise Paris and Sultan, {Charles S.} and Song, {Robert X.D.} and Laurence Demers and Bhaskar Sundaram and James Settlage and Susan Ohorodnik and Santen, {Richard J.}",
year = "2005",
month = "3",
day = "1",
doi = "10.1210/jc.2004-0766",
language = "English (US)",
volume = "90",
pages = "1407--1413",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

Wang, S, Paris, F, Sultan, CS, Song, RXD, Demers, L, Sundaram, B, Settlage, J, Ohorodnik, S & Santen, RJ 2005, 'Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women', Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 3, pp. 1407-1413. https://doi.org/10.1210/jc.2004-0766

Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women. / Wang, Shuping; Paris, Francoise; Sultan, Charles S.; Song, Robert X.D.; Demers, Laurence; Sundaram, Bhaskar; Settlage, James; Ohorodnik, Susan; Santen, Richard J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 3, 01.03.2005, p. 1407-1413.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women

AU - Wang, Shuping

AU - Paris, Francoise

AU - Sultan, Charles S.

AU - Song, Robert X.D.

AU - Demers, Laurence

AU - Sundaram, Bhaskar

AU - Settlage, James

AU - Ohorodnik, Susan

AU - Santen, Richard J.

PY - 2005/3/1

Y1 - 2005/3/1

N2 - A recent analysis of data from nine studies provided convincing evidence that plasma estradiol measurements predict the risk of breast cancer in normal postmenopausal women. However, the median values detected by the various assays used in this study varied by 5-fold. These and other published data in normal postmenopausal women suggest that assays measuring low plasma estradiol concentrations suffer from problems of sensitivity, specificity, and precision. Availability of a practical, low-cost, specific, precise, and ultrasensitive estrogen assay might allow enhanced prediction of the risk of breast cancer and provide an objective means of selecting postmenopausal women for breast cancer prevention. A recombinant cell ultrasensitive bioassay (RCUB) for estrogen was recently validated for use in prepubertal children. We postulated that the RCUB might also prove useful for measurement of postmenopausal levels and designed the present study to examine this possibility. Thirty normal postmenopausal volunteers provided blood samples for measurement of estrogen by RCUB and, for comparison, by RIA. The estrogenic activity measured by RCUB [mean ± SD, 11.9 ± 10.9 pmol/liter (SI units, 3.23 ±2.96 pg/ml)] was significantly lower than estradiol levels measured by RIA [43.7 ± 44.0 pmol/liter (11.9 ± 12.0 pg/ml)] in our volunteer subjects (P < 0.00001). Nonetheless, plasma estradiol levels measured by bioassay were significantly correlated with the estrogenic activity measured by RIA (r = 0.84) and by gas chromatography/tandem mass spectrometry (r = 0.85). To obtain biological evidence of the validity of the RCUB, we related plasma estrogen levels to body weight and body mass index and found highly significant correlations (r = 0.54 and r = 0.53, respectively). Surprisingly, 28 of 30 postmenopausal women were found to have estrogen levels in the prepubertal range with the RCUB. The levels detected by RCUB were similar to those previously reported using an ultrasensitive but less practical yeast bioassay. These results provide validation for the RCUB in postmenopausal women and suggest that it might prove useful for selection of women for drug therapy to prevent breast cancer.

AB - A recent analysis of data from nine studies provided convincing evidence that plasma estradiol measurements predict the risk of breast cancer in normal postmenopausal women. However, the median values detected by the various assays used in this study varied by 5-fold. These and other published data in normal postmenopausal women suggest that assays measuring low plasma estradiol concentrations suffer from problems of sensitivity, specificity, and precision. Availability of a practical, low-cost, specific, precise, and ultrasensitive estrogen assay might allow enhanced prediction of the risk of breast cancer and provide an objective means of selecting postmenopausal women for breast cancer prevention. A recombinant cell ultrasensitive bioassay (RCUB) for estrogen was recently validated for use in prepubertal children. We postulated that the RCUB might also prove useful for measurement of postmenopausal levels and designed the present study to examine this possibility. Thirty normal postmenopausal volunteers provided blood samples for measurement of estrogen by RCUB and, for comparison, by RIA. The estrogenic activity measured by RCUB [mean ± SD, 11.9 ± 10.9 pmol/liter (SI units, 3.23 ±2.96 pg/ml)] was significantly lower than estradiol levels measured by RIA [43.7 ± 44.0 pmol/liter (11.9 ± 12.0 pg/ml)] in our volunteer subjects (P < 0.00001). Nonetheless, plasma estradiol levels measured by bioassay were significantly correlated with the estrogenic activity measured by RIA (r = 0.84) and by gas chromatography/tandem mass spectrometry (r = 0.85). To obtain biological evidence of the validity of the RCUB, we related plasma estrogen levels to body weight and body mass index and found highly significant correlations (r = 0.54 and r = 0.53, respectively). Surprisingly, 28 of 30 postmenopausal women were found to have estrogen levels in the prepubertal range with the RCUB. The levels detected by RCUB were similar to those previously reported using an ultrasensitive but less practical yeast bioassay. These results provide validation for the RCUB in postmenopausal women and suggest that it might prove useful for selection of women for drug therapy to prevent breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=15944423253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15944423253&partnerID=8YFLogxK

U2 - 10.1210/jc.2004-0766

DO - 10.1210/jc.2004-0766

M3 - Article

VL - 90

SP - 1407

EP - 1413

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -