| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Special Feature |
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (K.K.M., J.H., G.S., A.K.) Boston, Massachusetts 02114; College of Physicians and Surgeons, Columbia University and St. Luke’s-Roosevelt Hospital Center (W.R.), New York, New York 10019; MGH Biostatistics Center and the Clinical Research Center, Massachusetts General Hospital and Harvard Medical School (H.L., D.S.), Boston, Massachusetts 02114; and General Clinical Research Center, Massachusetts General Hospital and Harvard Medical School (G.N.), Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Karen K. Miller, M.D., Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: kkmiller{at}partners.org.
Androgen deficiency in women is increasingly recognized as a new clinical syndrome and has raised our awareness of the importance of accurate and well-validated measurements of serum free testosterone (T) concentrations in women. Therefore, we compared serum free T levels measured by equilibrium dialysis to those measured by a direct RIA (analog method) and to those calculated from the law of mass action (requires the measurement of total T and SHBG). We also calculated the free androgen index, 100 x T/SHBG, as a simple index known to correlate with free T. Subjects were 147 women with variable androgen and estrogen statuses. All were studied three times in 1 month and included women 1) with regular menses (estrogen positive, T positive), 2) more than 50 yr old and not receiving estrogen (estrogen negative, T positive), 3) receiving estrogen (estrogen positive, T negative), and 4) with severe androgen deficiency secondary to hypopituitarism (estrogen negative, T negative). Calculated values for free T using the laws of mass action correlated well with those obtained from equilibrium dialysis (r = 0.99; P < 0.0001). However, the agreement depended strongly on the specific assays used for total T and SHBG. In contrast, the direct RIA method had unacceptably high systematic bias and random variability and did not correlate as well with equilibrium dialysis values (r = 0.81; P < 0.0001). In addition, the lower limit of detection was higher for the direct RIA than for equilibrium dialysis or calculated free T. Free androgen index correlates well with free T by equilibrium dialysis (r = 0.93; P < 0.0001), but is a unitless number without reference to the physical reality of free T. We conclude that the mass action equation and equilibrium dialysis are the preferred methods for use in diagnosing androgen deficiency in women.
This work was supported in part by NIH Grants M01-RR-01066, M01-RR-01066-27S1, and R03-DK-59297 and FDA Grant FD-R-001981.
Abbreviations: CV, Coefficient of variation; FAI, free androgen index; IRMA, immunoradiometric assay; ROC, receiver operator characteristic.
This article has been cited by other articles:
 |
|
 |
|
  J.-N. Hugues, L. Theron-Gerard, C. Coussieu, M. Pasquier, D. Dewailly, and I. Cedrin-Durnerin Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels Hum. Reprod., November 6, 2009; (2009) dep378v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Zethraeus, L. Kocoska-Maras, T. Ellingsen, B. von Schoultz, A. L. Hirschberg, and M. Johannesson A randomized trial of the effect of estrogen and testosterone on economic behavior PNAS, April 21, 2009; 106(16): 6535 - 6538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. August, S. Caprio, I. Fennoy, M. Freemark, F. R. Kaufman, R. H. Lustig, J. H. Silverstein, P. W. Speiser, D. M. Styne, and V. M. Montori Prevention and Treatment of Pediatric Obesity: An Endocrine Society Clinical Practice Guideline Based on Expert Opinion J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4576 - 4599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B d'Alva, G. Abiven-Lepage, V. Viallon, L. Groussin, M. A. Dugue, X. Bertagna, and J. Bertherat Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess Eur. J. Endocrinol., November 1, 2008; 159(5): 641 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Utz, A. Yamamoto, P. Sluss, J. Breu, and K. K. Miller Androgens May Mediate a Relative Preservation of IGF-I Levels in Overweight and Obese Women Despite Reduced Growth Hormone Secretion J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 4033 - 4040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Martin, R. J. Chang, D. A. Ehrmann, L. Ibanez, R. A. Lobo, R. L. Rosenfield, J. Shapiro, V. M. Montori, and B. A. Swiglo Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1105 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Swerdloff and C. Wang Free Testosterone Measurement by the Analog Displacement Direct Assay: Old Concerns and New Evidence Clin. Chem., March 1, 2008; 54(3): 458 - 460. [Full Text] [PDF]
|
|
|
|
|
|
K. S. Fritz, A. J.S. McKean, J. C. Nelson, and R. B. Wilcox Analog-Based Free Testosterone Test Results Linked to Total Testosterone Concentrations, Not Free Testosterone Concentrations Clin. Chem., March 1, 2008; 54(3): 512 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Miller, E. A. Lawson, V. Mathur, T. L. Wexler, E. Meenaghan, M. Misra, D. B. Herzog, and A. Klibanski Androgens in Women with Anorexia Nervosa and Normal-Weight Women with Hypothalamic Amenorrhea J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1334 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Cappola, S. J. Ratcliffe, S. Bhasin, M. R. Blackman, J. Cauley, J. Robbins, J. M. Zmuda, T. Harris, and L. P. Fried Determinants of Serum Total and Free Testosterone Levels in Women over the Age of 65 Years J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 509 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Rosner, R. J. Auchus, R. Azziz, P. M. Sluss, and H. Raff Utility, Limitations, and Pitfalls in Measuring Testosterone: An Endocrine Society Position Statement J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 405 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Chang, S. M. Abdullah, T. Jain, H. G. Stanek, S. R. Das, D. K. McGuire, R. J. Auchus, and J. A. de Lemos Associations Among Androgens, Estrogens, and Natriuretic Peptides in Young Women: Observations From the Dallas Heart Study J. Am. Coll. Cardiol., January 2, 2007; 49(1): 109 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Azziz, E. Carmina, D. Dewailly, E. Diamanti-Kandarakis, H. F. Escobar-Morreale, W. Futterweit, O. E. Janssen, R. S. Legro, R. J. Norman, A. E. Taylor, et al. Criteria for Defining Polycystic Ovary Syndrome as a Predominantly Hyperandrogenic Syndrome: An Androgen Excess Society Guideline J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4237 - 4245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wierman, R. Basson, S. R. Davis, S. Khosla, K. K. Miller, W. Rosner, and N. Santoro Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3697 - 3710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. de Ronde, Y. T. van der Schouw, H. A.P. Pols, L. J.G. Gooren, M. Muller, D. E. Grobbee, and F. H. de Jong Calculation of Bioavailable and Free Testosterone in Men: A Comparison of 5 Published Algorithms Clin. Chem., September 1, 2006; 52(9): 1777 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Parsons, H. B. Carter, A. W. Partin, B. G. Windham, E. J. Metter, L. Ferrucci, P. Landis, and E. A. Platz Metabolic Factors Associated with Benign Prostatic Hyperplasia J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2562 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Bilezikian What's Good for the Goose's Skeleton is Good for the Gander's Skeleton. J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1223 - 1225. [Full Text] [PDF]
|
|
|
|
|
|
E. Orwoll, L. C. Lambert, L. M. Marshall, K. Phipps, J. Blank, E. Barrett-Connor, J. Cauley, K. Ensrud, S. Cummings, and for the Osteoporotic Fractures in Men Study Group Testosterone and Estradiol among Older Men J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1336 - 1344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Ding, Y. Song, V. S. Malik, and S. Liu Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis JAMA, March 15, 2006; 295(11): 1288 - 1299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Rosenfield Hirsutism N. Engl. J. Med., December 15, 2005; 353(24): 2578 - 2588. [Full Text] [PDF]
|
|
|
|
 |
|
 F Labrie, V Luu-The, A Belanger, S-X Lin, J Simard, G Pelletier, and C Labrie Is dehydroepiandrosterone a hormone? J. Endocrinol., November 1, 2005; 187(2): 169 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Parsons, H. B. Carter, E. A. Platz, E. J. Wright, P. Landis, and E. J. Metter Serum Testosterone and the Risk of Prostate Cancer: Potential Implications for Testosterone Therapy Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2257 - 2260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Davis, S. L. Davison, S. Donath, and R. J. Bell Circulating Androgen Levels and Self-reported Sexual Function in Women JAMA, July 6, 2005; 294(1): 91 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Pitteloud, V. K. Mootha, A. A. Dwyer, M. Hardin, H. Lee, K.-F. Eriksson, D. Tripathy, M. Yialamas, L. Groop, D. Elahi, et al. Relationship Between Testosterone Levels, Insulin Sensitivity, and Mitochondrial Function in Men Diabetes Care, July 1, 2005; 28(7): 1636 - 1642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Davison, R. Bell, S. Donath, J. G. Montalto, and S. R. Davis Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3847 - 3853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Lovering and W. A. Romani Effect of testosterone on the female anterior cruciate ligament Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R15 - R22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Pitteloud, M. Hardin, A. A. Dwyer, E. Valassi, M. Yialamas, D. Elahi, and F. J. Hayes Increasing Insulin Resistance Is Associated with a Decrease in Leydig Cell Testosterone Secretion in Men J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2636 - 2641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Davison, J. Thipphawong, J. Blanchard, K. Liu, R. Morishige, I. Gonda, J. Okikawa, J. Adams, A. Evans, B. Otulana, et al. Pharmacokinetics and Acute Safety of Inhaled Testosterone in Postmenopausal Women J. Clin. Pharmacol., February 1, 2005; 45(2): 177 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Van Uytfanghe, D. Stockl, J. M. Kaufman, T. Fiers, H. A. Ross, A. P. De Leenheer, and L. M. Thienpont Evaluation of a Candidate Reference Measurement Procedure for Serum Free Testosterone Based on Ultrafiltration and Isotope Dilution-Gas Chromatography-Mass Spectrometry Clin. Chem., November 1, 2004; 50(11): 2101 - 2110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.M. Rivera-Woll, M. Papalia, S.R. Davis, and H.G. Burger Androgen insufficiency in women: diagnostic and therapeutic implications Hum. Reprod. Update, September 1, 2004; 10(5): 421 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Matsumoto and W. J. Bremner Serum Testosterone Assays--Accuracy Matters J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 520 - 524. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
