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Original Studies |
Laboratory for Hormonology and Department of Endocrinology, University Hospital Ghent, 9000 Ghent, Belgium
Address all correspondence and requests for reprints to: Dr. J. M. Kaufman, University Hospital, 9K12 IE Endocrinology, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: jean.kaufman{at}rug.ac.be
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Abstract |
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The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index of bioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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T bound to albumin represents the nonspecifically bound T fraction (1) and is linearly related to free T (FT): AT = KaCa x FT, where AT is the albumin-bound T, Ka is the association constant of albumin for T, Ca is the albumin concentration, and FT is the free T fraction. The sum of FT and AT (i.e. the non-SHBG-bound T) is for convenience often referred to as bioavailable fraction in plasma. As the total serum T concentration is subject to variations in the concentration of the binding proteins, it is not a reliable index of bioavailable T. For example, in hyperthyroidism T levels are high, whereas bioavailable T levels are normal (2). Hence, there is a clinical need for a reliable index of bioavailable androgens.
Several methods have been used to estimate free or bioavailable T in plasma. FT can be measured by equilibrium dialysis [apparent FT concentration (AFTC)] (2), the method of choice for measurement of the free fraction of steroids in vivo (3). Alternatively, the non-SHBG-bound, biologically readily available fraction may be obtained by precipitation of SHBG-bound T with ammonium sulfate (non-SHBG-T) (4, 5). As both are rather time-consuming procedures, many researchers use an indirect parameter of FT, the free androgen index (FAI), which is obtained as the quotient 100 T/SHBG (6). FT can also be estimated directly by an immunoassay method involving an analog ligand (aFT). The latter technique is often considered the easiest and fastest method for measuring FT (3), but the values obtained with this analog ligand immunoassay are substantially lower than values obtained by dialysis (7, 8).
At equilibrium, binding of T to plasma proteins can be represented by
Eq I: T = FT + P1T +
P2T + P3T... . .
+PnT (). For each protein, applying the law
of mass action, we have: [FT] + [P] 
[PT] or [FT] =
([PT]/(K x [P])), and in the presence of several binding
proteins: [FT] =
([P1T]/(K1 x
[P1])) =
[P2T]/(K2 x
[P2])) = . . . . . =
([PnT]/(Kn x
[Pn])) (Eq II), where
[P1T], [P2T], . . .
[PnT] are the concentrations of T bound to
proteins 1, 2, . . . n, respectively; K1,
K2, . . . Kn are the
association constants of proteins 1, 2, . . . n, respectively, for
T; and [P1], [P2], . .
. [Pn] are the free binding sites on protein 1,
2, . . . n, respectively. As the binding capacity of albumin is
very high with respect to the concentration of T, the following
equation holds true for the ratio of albumin-bound T (AT) to unbound T:
(AT/FT) = KaCa or
AT = (FT x KaCa)
(Eq III), where Ka equals 3.6 x
104 L/Mol (9, 10); Ca is
the albumin concentration, i.e. ± 43 g/L or (mol wt,
69,000) ± 6.2 x 10-4 mol/L; and
KaCa is ± 22.
The only other protein that binds T is SHBG; binding of T to transcortin or orosomucoid is negligible (2). As the binding of other steroid hormones normally present in plasma can be omitted from the calculation (9), it follows: FT = ([T] - (N x [FT]))/(Kt{SHBG - [T] + N[FT]}) (Eq IV), where Kt is the association constant of SHBG for T, and N = KaCa + 1. This yields a second degree equation that can be solved either for FT or SHBG (2, 7, 9).
Several immunoassay methods are available for measurement of serum SHBG levels. If the concentration of immunoassayable SHBG (iSHBG) is a reliable measure of SHBG binding capacity (11), a reliable value of FT can thus easily be calculated. Conversely, when the AFTC is determined by equilibrium dialysis, the SHBG binding capacity (cSHBG) can be calculated.
It is surprising that whereas calculation of free T from total T and iSHBG is a simple and rapid procedure, the reliability of the calculated FT has never been extensively studied by comparing these values to those obtained by dialysis (AFTC). Indeed, Södergaard et al. (11) calculated FT from SHBG and albumin concentrations, but did not validate the method, whereas Wilke and Utley (7) compared calculated FT values in women to data obtained by direct analog ligand immunoassay of FT (aFT), but not to AFTC. The manufacturer of a kit for aFT measurement claims that aFT corresponds to 0.42 AFTC + 9.8 pg/mL (r = 0.67) in males and to 0.79 AFTC + 1.07 pg/mL (r = 0.75) in women, but values obtained in clinical routine appear to be substantially lower (7, 8).
It is thus not surprising that there are substantial discrepancies in the literature concerning the free or non-SHBG-bound bioavailable T levels obtained by a variety of only partially validated methods, as has recently been illustrated (8). We decided therefore to compare the AFTC values, generally considered as the index of choice for evaluation of free T levels, to calculated FT and aFT levels as well as to the FAI in sera from subjects with normal, low, and high SHBG binding capacities, respectively. Finally, we also compared the non-SHBG-T obtained by the ammonium sulfate precipitation technique with the FT levels as well as the nonspecifically bound T levels, calculated from T and iSHBG (i.e., FT x N).
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Total serum T was measured by RIA using a commercial kit (Biosource Technologies, Inc., Fleurus, Belgium). Concentrations are given in nanomoles per L; for conversion to nanograms per dL, multiply by 28.84. The interassay coefficient of variation (CV) is below 10% for the whole concentration range.
Serum concentrations of SHBG were measured by immunoradiometric assay (IRMA), using a commercial kit (Orion Dignostica, Espoo, Finland) and are referred to as iSHBG; the interassay CV is 8%.
In our reference procedure for estimation of free T, AFTC is obtained from serum total T and the free T fraction determined by equilibrium dialysis on diluted serum at 37 C with use of [3H]T as described previously (2, 9); the SHBG binding capacity is calculated from AFTC using the above-mentioned second degree equation (see introduction; Eq IV), taking a value of 1 x 109 L/mol for the association constant of SHBG for T at 37 C and a value of 3.6 x 104 L/mol for that of albumin for T (10); this value is corrected for serum dilution, and AFTC in undiluted serum is then calculated. The interassay CV is 7.8%. The SHBG binding capacities thus calculated from AFTC are further referred to as cSHBG.
The same second degree equation (introduction; Eq IV) is used for calculation of FT from serum total T and serum iSHBG measured by IRMA. The FAI is calculated from total T and iSHBG: FAI = (100 x T)/SHBG (Eq V), with both T and SHBG expressed in nanomoles per L (6).
Direct estimation of serum free T by an analog ligand RIA (aFT) was performed using a commercial kit from Diagnostic Products (Los Angeles, CA); the binding capacity of SHBG calculated from aFT using the above-mentioned second degree equation is further referred to as aSHBG.
Non-SHBG-T was obtained from serum total T and determination of the non-SHBG-bound T fraction by ammonium sulfate precipitation, the method involving incubation with a tracer dose of [3H]T at 37 C, and precipitation of SHBG-bound hormone with ammonium sulfate at a final concentration of 50%, followed by centrifugation and counting of radioactivity in the supernatant (5).
Serum samples
Sera from men were obtained from a randomly selected subgroup of sera from healthy, ambulant men participating in a population study on the influence of age on plasma T levels.
Sera from postmenopausal women were obtained from women consulting the menopause clinic for check-up. Pregnancy sera were obtained in third trimester pregnancy. Sera were also obtained from hyperthyroid subjects; hyperthyroidism was confirmed on the basis of suppressed TSH with elevated FT4 and FT3 levels. Finally, sera were also obtained from a small group of women investigated for mild clinical hyperandrogenism.
Statistics
Correlation of results obtained by different methods was estimated using the method of least square regression.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In a first series of experiments we compared the FT values calculated from serum T using the iSHBG and the actual measured albumin serum concentration to the AFTC determined by equilibrium dialysis in a group of ambulant men (n = 28), aged 25–80 yr, with serum T concentrations varying between 1.63–31.0 nmol/L.
As can be seen in Fig. 1a
, AFTC and FT
values differed very little; the mean values (±SEM) were
330 ± 36.4 and 332 ± 37.1 pmol/L for AFTC and FT (FT =
1.002 AFTC + 0.877 pmol/L), respectively, with a correlation
coefficient of 0.987.
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).
A similar study was performed with sera from 32 postmenopausal
women with T concentrations ranging from 461-1553 pmol/L. The FT
concentrations (mean ± SEM, 11.4 ± 1.04 pmol/L)
were almost identical to AFTC concentrations (11.1 ± 1.04 pmol/L;
FT = 0.949 AFTC + 1.14 pmol/L; r = 0.966; Fig. 1c). To assess
whether the close correlation between FT and AFTC persisted in subjects
with high SHBG, we performed a similar study using sera (n = 18)
from patients of either sex with hyperthyroidism (SHBG, 41–204
nmol/L). Again, similar values were obtained by both methods; mean
(±SEM) FT and AFTC were 142 ± 30.5 and 146 ±
31.6 pmol/L, respectively (FT = 0.951 AFTC + 3.16
pMol/L; r = 0.982; Fig. 1d). A similar study was
performed on sera from a small group of women with mild clinical
hyperandrogenism (n = 12); the mean (±SE) AFTC and FT
were 25.0 ± 3.12 and 22.9 ± 2.77 pmol/L, respectively
(FT = 0.850 AFTC + 1.56 pmol/L), with a correlation coefficient of
0.979.
Finally, we compared FT levels to AFTC levels obtained for third
trimester (weeks 24–37) pregnancy sera (n = 16). As the mean
albumin concentration was only 32 ± 1 g/L (4.6 ± 0.14
x 10-4 mol/L), we used the actual albumin
concentration in the calculation. The mean (±SEM) value
for AFTC (14.6 ± 1.73 pmol/L) was significantly higher than that
for FT (10.06 ± 1.39 pmol/L; FT = 0.713 AFTC - 0.217
pmol/L; r = 0.926; Fig. 1e).
Comparison of aFT and AFTC
In the next series of experiments we compared the aFT levels as
measured directly by analog ligand RIA to AFTC levels. In a group of 28
men, mean (±SEM) aFT values (65.5 ± 7.28 pmol/L)
were only a fraction (one fifth) of AFTC values (303 ± 34.0
pmol/L; aFT = 0.186 AFTC + 4.38 pmol/L), albeit there was a
significant correlation between these values (r = 0.937; Fig. 2a). In sera from women (n = 8), aFT
(mean ± SEM, 4.85 ± 0.832 pmol/L) was around
30% of AFTC values (15.95 ± 4.27 pmol/L). Our data furthermore
suggest that there exists a positive correlation (P <
0.05) between the specific binding capacity for T (i.e.
cSHBG) and the aFT/AFTC ratio (Fig. 2b).
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Comparison of FAI and AFTC
We next evaluated the reliability of the FAI (FAI = 100
T/iSHBG) as a parameter of bioavailable T. This parameter,
obtained in 28 healthy subjects, was highly significantly correlated
with AFTC (r = 0.848; FAI = 0.132 AFTC + 7.273; Fig. 3a). However, the ratio FAI/AFTC varied
from 0.12–0.26, indicating that in the individual case FAI is a rather
unreliable index of bioavailable T. In 18 hyperthyroid subjects, the
correlation coefficient was 0.946 (Fig. 3b), whereas the FAI/AFTC ratio
varied between 0.17–0.39. The FAI/AFTC ratio is negatively correlated
with the number of free binding sites on SHBG (cSHBG -
cSHBG-T; Fig. 3c).
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As iSHBG concentrations are not necessarily identical to the concentrations of binding sites (cSHBG), we compared iSHBG to cSHBG values calculated assuming an albumin concentration of 43g/L. In 28 normal men, the mean (±SEM) cSHBG was 56.1 ± 5.06 nmol/L compared to 48.04 ± 4.48 nmol/L for iSHBG (SHBG = 1.09 iSHBG + 3.64 nmol/L; r = 0.963). In our series of hyperthyroid subjects (n = 18), the mean iSHBG concentration was 96.6 ± 11.58 nmol/L in comparison with a cSHBG of 93.9 ± 10.98 nmol/L (0.962 cSHBG + 6.238 nmol/L; r = 0.912). A close correlation between iSHBG (mean ± SEM, 54.25 ± 5.30 nmol/L) and cSHBG (49.96 ± 6.32 nmol/L) was also observed in sera from women with clinical hyperandrogenism (r = 0.977; iSHBG = 0.820 cSHBG + 13.273 nmol/L), whereas in a group of 32 postmenopausal women, at low T levels the correlation coefficient was only 0.806. In the third trimester pregnancy sera, for which AFTC values were higher than FT values, cSHBG values calculated from AFTC were correspondingly significantly lower (mean ± SEM, 161.7 ± 7.09 nmol/L) than iSHBG (198.0 ± 2.6 nmol/L).
Comparison of non-SHBG-T and FT
As at least part of the albumin-bound T is bioavailable, we
compared non-SHBG-T determined by the ammonium sulfate precipitation
technique to FT and to the calculated nonspecifically bound T
(i.e. non-SHBG-bound T) in 24 subjects of either sex with T
concentrations varying between 0.485–25.2
nMol/L. As shown in Fig. 4, the correlation coefficient for
non-SHBG-T vs. FT was 0.974, with non-SHBG-T corresponding
to approximately 20 times FT, whereas the nonspecifically bound T
calculated from T and iSHBG, assuming a fixed albumin concentration of
6.12 x 10-4 mol/L, was ±23 times FT, with
a similar correlation coefficient as for FT, nonspecifically bound T
being a multiple of FT.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Direct measurement of the FT concentration by an analog ligand immunoassay procedure is an attractive and simple alternative. Our study indicates, however, that the direct measurement of aFT by analog ligand RIA, although showing a generally good correlation with AFTC, is not a reliable index of FT; the aFT represents a variable fraction (20–60%) only of AFTC. This is confirmed by the fact that calculation of the SHBG binding capacity from aFT (aSHBG) yields values that are multiples of all values previously reported in the literature. Similar findings were reported by Wilke and Utley (7) as well as by Rosner (8). Our data show, moreover, that the aFT/AFTC ratio is SHBG dependent. Winters et al. (13) arrived at a similar conclusion.
The FAI also appears not to be a reliable index of FT. Indeed, the
ratio FAI/AFTC, which should be constant if FAI reflects AFTC, varies
in fact by as much as a factor of 2.5. Combining Eq III, IV, and V (see
introduction and Materials and Methods), one obtains:
FAI/FT = (100[(SHBG - SHBG-T)-K + N])/SHBG. From the
latter equation it follows that the FAI/AFTC ratio is correlated to the
number of free binding sites on SHBG (Fig. 3c). The FAI/AFTC ratio will
be high when the number of occupied binding sites is small related to
the SHBG binding capacity (e.g. in women), whereas the ratio
will, conversely, be low when a substantial proportion of the binding
sites is occupied (e.g. in adult men). Based on a similar
calculation, Kapoor et al. (14) came to the conclusion that
the FAI is not valid for adult males.
The overall excellent correspondence between FT and AFTC levels indicates that FT is a reliable index of unbound T. Calculation of FT from total T and immunoassayable SHBG represents a simple and rapid method that under all conditions studied, except for pregnancy serum, yielded values very close, if not identical, to those obtained by equilibrium dialysis (AFTC).
Whereas our data show that within the physiological range of 40–50 g/L (5.8–7.2 x 10-4 mol/L), the albumin concentration does not significantly affect FT values, it should be realized that this is only valid for these physiological concentrations. Moreover, there is good evidence that at least part of the albumin-bound T might be bioavailable (1). Hence, when the albumin concentration is expected to deviate significantly from normalcy, the actual albumin concentration should be determined, and FT and albumin-bound T calculated accordingly.
Such a situation exists during pregnancy. In our third trimester sera, the mean albumin concentration was 32 ± 1 g/L. Hence, the actual albumin concentration had to be used to calculate FT and cSHBG, and although the AFTC is higher than that in nonpregnant women, the nonspecifically bound T concentration is in the normal range. Bammann et al. (15) as well as Wilke and Utley (7) observed increased AFTC as well as FT levels in pregnancy serum, although, as they pointed out, increased androgenicity is not a normal clinical feature of pregnancy. The normal concentrations for the bioavailable, albumin-bound T may explain the absence of virilization in the presence of increased FT and AFTC.
As to the observed differences between AFTC and FT concentrations, and thus between cSHBG and iSHBG concentrations in pregnancy serum, this is the consequence of the occupation of a substantial fraction of the SHBG-binding sites by estradiol. Indeed, AFTC as determined by dialysis is dependent upon the number of binding sites available for T. In the presence of competing steroids in concentrations corresponding to a substantial fraction of the T concentration, cSHBG will be significantly lower than iSHBG, as the latter measures all SHBG molecules regardless of whether they are available for T binding. Knowing the estradiol concentration as well as the association constants of estradiol for albumin and SHBG, the concentration of estradiol bound to SHBG can be calculated. For term pregnancy, with an estradiol concentration around 20 ng/ml (73.4 nmol/L), it can be calculated that about 50 nmol/L SHBG is occupied by estradiol and not available for T binding; this explains why the calculated cSHBG is significantly lower than the iSHBG value measured by IRMA, whereas FT is falsely lower than AFTC as a consequence of inclusion of the binding sites actually occupied by estradiol in the calculation of FT.
The excellent correlation of non-SHBG-T with FT and with the calculated nonspecifically bound T, which is a multiple of FT, respectively, is a strong argument in support of the validity of the calculated nonspecifically bound T as a parameter of the bioavailable fraction of T. Non-SHBG-T measured by ammonium sulfate precipitation was around 20 times the FT, whereas the calculated nonspecifically bound T, using an association constant of albumin for T of 3.6 x 104 L/mol, was around 23 times the FT. The value for the association constant, which is obtained using pure human albumin, might be slightly lower in serum due to the presence of lipids, in which case N (KaCa + FT) might be closer to 20. In any case, the calculated nonspecifically bound T reliably reflects the non-SHBG-T.
In conclusion, this study shows that neither aFT nor FAI is a reliable parameter of FT. The similar values of FT and AFTC as well as iSHBG and cSHBG obtained under various physiopathological conditions, provided no competing steroids are present in a high concentration, show that the calculated FT is a reliable index of FT, that calculated nonspecifically bound T reflects reliably non-SHBG-T (bioavailable T), and that immunoassayable SHBG is a reliable measure of SHBG-binding sites.
Received April 5, 1999.
Revised July 7, 1999.
Accepted July 12, 1999.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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J. S. Lee, A. Z. LaCroix, L. Wu, J. A. Cauley, R. D. Jackson, C. Kooperberg, M. S. Leboff, J. Robbins, C. E. Lewis, D. C. Bauer, et al. Associations of Serum Sex Hormone-Binding Globulin and Sex Hormone Concentrations with Hip Fracture Risk in Postmenopausal Women J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1796 - 1803. [Abstract] [Full Text] [PDF]
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 J. A. Talbot, R. Sheldrick, H. Caswell, and S. Duncan Sexual function in men with epilepsy: How important is testosterone? Neurology, April 15, 2008; 70(16): 1346 - 1352. [Abstract] [Full Text] [PDF]
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M. Mohlig, M. O Weickert, E. Ghadamgahi, A. M Arafat, J. Spranger, A. F H Pfeiffer, and C. Schofl Retinol-binding protein 4 is associated with insulin resistance, but appears unsuited for metabolic screening in women with polycystic ovary syndrome. Eur. J. Endocrinol., April 1, 2008; 158(4): 517 - 523. [Abstract] [Full Text] [PDF]
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L. J. Shaw, C. N. Bairey Merz, R. Azziz, F. Z. Stanczyk, G. Sopko, G. D. Braunstein, S. F. Kelsey, K. E. Kip, R. M. Cooper-DeHoff, B. D. Johnson, et al. Postmenopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health--National Heart, Lung, and Blood Institute Sponsored Women's Ischemia Syndrome Evaluation J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1276 - 1284. [Abstract] [Full Text] [PDF]
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A. Mueller, L. J. Gooren, S. Naton-Schotz, S. Cupisti, M. W. Beckmann, and R. Dittrich Prevalence of Polycystic Ovary Syndrome and Hyperandrogenemia in Female-to-Male Transsexuals J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1408 - 1411. [Abstract] [Full Text] [PDF]
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K. Allvin, C. Ankarberg-Lindgren, H. Fors, and J. Dahlgren Elevated Serum Levels of Estradiol, Dihydrotestosterone, and Inhibin B in Adult Males Born Small for Gestational Age J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1464 - 1469. [Abstract] [Full Text] [PDF]
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E. Elaut, G. De Cuypere, P. De Sutter, L. Gijs, M. Van Trotsenburg, G. Heylens, J.-M. Kaufman, R. Rubens, and G. T'Sjoen Hypoactive sexual desire in transsexual women: prevalence and association with testosterone levels Eur. J. Endocrinol., March 1, 2008; 158(3): 393 - 399. [Abstract] [Full Text] [PDF]
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M. Das, O. Djahanbakhch, B. Hacihanefioglu, E. Saridogan, M. Ikram, L. Ghali, M. Raveendran, and A. Storey Granulosa Cell Survival and Proliferation Are Altered in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 881 - 887. [Abstract] [Full Text] [PDF]
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 O. P. Almeida, B. B. Yeap, G. J. Hankey, K. Jamrozik, and L. Flicker Low Free Testosterone Concentration as a Potentially Treatable Cause of Depressive Symptoms in Older Men Arch Gen Psychiatry, March 1, 2008; 65(3): 283 - 289. [Abstract] [Full Text] [PDF]
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 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]
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