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Original Studies |
Department of Internal Medicine III (A.W.v.d.B., F.H.d.J., H.A.P.P., S.W.J.L.), Erasmus University Rotterdam, 3015 GD Rotterdam; and Julius Center for Patient Oriented Research (A.W.v.d.B., D.E.G.), Utrecht University Hospital, Utrecht 3584 CX, The Netherlands
Address correspondence and requests for reprints to: Annewieke W. van den Beld, Department of Internal Medicine III, Room D433, University Hospital Dijkzigt, 40 Dr. Molenwaterplein, 3015 GD Rotterdam, The Netherlands. E-mail: vandenbeld{at}inw3.azr.nl
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Abstract |
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After exclusion of subjects with severe mobility problems and signs of dementia, 403 healthy men (age, 73–94 yr) were randomly selected from a population-based sample. Total T (TT), free T (FT), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were determined by RIA. Levels of non-SHBG-bound T (non-SHBG-T), FT (calc-FT), the TT/SHBG ratio, non-SHBG-bound E2, and free E2 were calculated. Physical characteristics of aging included muscle strength measured using dynamometry, total body bone mineral density (BMD), hip BMD, and body composition, including lean mass and fat mass, measured by dual-energy x-ray absorptiometry.
In this population of healthy elderly men, calc-FT, non-SHBG-T, E1, and E2 (total, free, and non-SHBG bound) decreased significantly with age. T (total and non-SHBG-T) was positively related with muscle strength and total body BMD (for non-SHBG-T, respectively, ß = 1.93 ± 0.52, P < 0.001 and ß = 0.011 ± 0.002, P < 0.001). An inverse association existed between T and fat mass (ß = -0.53 ± 0.15, P < 0.001). Non-SHBG-T and calc-FT were more strongly related to muscle strength, BMD, and fat mass than TT and were also significantly related to hip BMD. E1 and E2 were both positively, independently associated with BMD (for E2, ß = 0.21 ± 0.08, P < 0.01). Non-SHBG-bound E2 was slightly strongly related to BMD than total E2. The positive relation between T and BMD was independent of E2. E1 and E2 were not related with muscle strength or body composition.
In summary, bioavailable T, E1, total E2, and bioavailable E2 all decrease with age in healthy old men. In this cross-sectional study in healthy elderly men, non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T, which seems to play a direct role in the various physiological changes that occur during aging. A positive relation with muscle strength and BMD and a negative relation with fat mass was found. In addition, both serum E1 and E2 seem to play a role in the age-related bone loss in elderly men, although the cross-sectional nature of the study precludes a definitive conclusion. Non-SHBG-bound E2 seems to be the best parameter of serum bioactive E2 in describing its positive relation with BMD.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Recently it has been suggested that estrogens may play an important role in the development and maintenance of the male skeleton (11). Several studies have reported positive relations between serum estradiol (E2) concentrations and bone mineral density (BMD) or bone turnover markers in men (12).
Serum T as well as E2 are mainly bound to sex-hormone binding globulin (SHBG) and albumin. It has been suggested that the fraction of T bound to albumin has access to target tissues (13). It remains to be established whether total, non-SHBG-bound (albumin bound and free) or free T (FT) levels are the best representation of the bioactive hormone concentrations. The same holds true for serum E2 concentrations.
Therefore, in the present cross-sectional study of 403 independently living elderly men, we tested the hypothesis that the decreases in bone mass, body composition, and muscle strength with age are related to the fall in circulating endogenous T and estrogen concentrations. We compared various measures of the level of bioactive androgen to which tissues are exposed: total T (TT) and FT levels in serum, the TT/SHBG ratio, calculated free and non-SHBG-bound T levels and TT adjusted for SHBG. In addition, relationships with total, non-SHBG-bound, and free estradiol (fE2) were compared.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The study is a cross-sectional, single-center study in 403 independently living men, 70 yr of age and higher. Names and addresses of all male inhabitants 70 yr and older were drawn from the municipal register of Zoetermeer, a medium sized town in the midwestern part of The Netherlands. A total of 1567 men were invited, and after exclusion of subjects who did not live independently and subjects who were not physically or mentally able to visit the study center independently, eventually 403 men participated (25.7%). A total of 886 men did not respond to the mailed invitation in which it was already mentioned that subjects who did not live independently or with severe mobility problems would not be allowed to participate. The main reason not to participate among the respondents was because they were already being seen by a specialist or general practitioner at the moment (28%), whereas 16% were excluded on the basis of physical (10%) or mental (6%) problems. Participants signed an informed consent. The study has been approved by the Medical Ethics Committee of the Erasmus University Hospital Rotterdam. No additional health-related eligibility criteria were used. A number of participants were taking medications for chronic illnesses, like hypertension (n = 96) and mild congestive heart failure (n = 28). However, none of these medications, in retrospect, influenced the relations described in this study. Some of the illnesses, for example mild knee pain (n = 79), influenced the physical characteristics measured, but, in retrospect, they did not change the relations between the physical characteristics nor between the circulating hormone levels and the physical characteristics reported in this study.
Hormone measurements
Blood samples were collected in the morning after an overnight
fast. The period of storage at -40C varied from 0–5 months. Serum
concentrations of TT (nmol/L), FT (nmol/L), and SHBG (nmol/L) were all
measured by RIA using commercial kits (Diagnostic Systems Laboratories,
Webster, TX). The intra assay coefficients of variation (CV) for these
assays were 8.1%, 6.2%, and 3.0%, respectively. The interassay CV
were 10.5%, 9.7%, and 4.4%. The FT RIA uses an
[I-125]-labeled T analog, which has a low affinity for
SHBG and albumin. This analog competes with the unbound T in the test
sample for binding to specific anti-T polyclonal antibodies that have
been immobilized on the assay tube. This competitive binding format
allows direct estimation of unlabeled FT levels in unextracted samples.
Furthermore, as measures of biologically active T, the TT/SHBG ratios
were calculated, as well as FT (calc-FT, nmol/L) and non-SHBG-bound T
(non-SHBG-T, nmol/L, is calc-FT plus albumin-bound T) (Table 1
) (14). In these
calculations, the possible binding of other steroids to SHBG was
disregarded. Finally, TT adjusted for SHBG in a multiple regression
analysis was used as a measure of non-SHBG-bound T.
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Physical characteristics of aging
Muscle strength. Isometric grip strength (IGS) was measured using an adjustable hand held dynamometer (JAMAR dynamometer) at the nondominant hand (15). Each test was repeated three times, and the average was used in the analyses. Leg or knee extensor strength (LES) was measured as described previously (16, 17), using the Hoggan MicroFET hand-held dynamometer. To obtain one main outcome measurement for LES, "maximum LES" (maxLES) was defined as the maximum strength for the right or left leg, whichever is largest, in a position of 120-degree extension. Statistical analyses were based on the physical unit momentum (Nm), obtained by multiplying the maximum strength (in Newton) and the distance of the dynamometer to the knee joint (in meters).
BMD and body composition
Total body BMD (TBBMD) was measured using dual-energy x-ray absorptiometry (Lunar, Madison, WI), as were hip BMDs at the femoral neck, trochanter, and Ward’s triangle (18). In addition, total and trunk lean body mass and fat mass were measured (19, 20). Quality assurance for dual-energy x-ray absorptiometry, including calibration, was performed every morning, using the standard provided by the manufacturer.
Height and weight were measured in standing position without shoes. Body mass index (BMI) was calculated as the weight in kilograms divided by the square of the height in meters. The waist circumference was measured at the level of the umbilicus, and the hip circumference was measured at the level of the greater trochanter. The average of two readings was used in the analyses. Waist to hip ratio, which represents a measure of upper body adiposity, was calculated from these two measurements.
Data analyses. Results were expressed, unless otherwise stated, as mean and SD with the interquartile range. Comparisons between groups were made by using Student’s t test. Differences were given together with the 95% confidence interval. Relations between variables were assessed using linear regression for continuous variables and logistic regression for binary variables and described as the linear regression coefficient (ß) and its SE. Multiple regression analysis was used to adjust for age and BMI, as well as to assess the contribution of different independent variables to the dependent variable. To assess the contribution of different variables on the dependent parameter, we used standardized regression, described as the standardized regression coefficient (B). Bs are regression coefficients normalized by the ratio of the SD of the dependent variable. Correlations between variables were assessed by using Pearson’s correlation coefficient r. All analyses were done using STATA Statistical Software, Release 5.0 (Stata Corporation, Texas).
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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. Muscle
strength, BMD, lean body mass, and fat mass all decreased with age in
our study group (Table 3). Because
virtually all parameters were related with age, all further analyses
were done after adjustment for age. Descriptive data of the hormone
measurements are shown in Table 4.
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The relations of the hormone measurements with age are shown in
Table 5. In our population, all T
measurements, except TT, significantly decreased with age. The relation
between non-SHBG-bound T and age is illustrated in Fig. 1. Serum SHBG and percentages of
SHBG-bound T and E2 increased with age. E1 and
total E2 concentrations were inversely related with age.
Calculated fE2 and calculated non-SHBG-bound E2
(non-SHBG-E2) decreased relatively more with age compared
with total E2 (Bs were, respectively, -0.15, -0.15, and
-0.12).
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Lean mass, fat mass, and maxLES were all positively, independently related with TBBMD [respectively, ß = 0.0060 ± 0.0008 kg/(g/cm2), P < 0.001; ß = 0.0063 ± 0.0008 kg/(g/cm2), P < 0.001; and ß = 0.0011 ± 0.0002 Nm/(g/cm2), P < 0.001]. Lean mass and maxLES were both positively associated (ß = 0.12 ± 0.01 Nm/kg, P < 0.001).
Relations between hormone concentrations
Mean values of measured FT were significantly lower than calc-FT
(difference 0.16 ± 0.003 nmol/L, confidence interval =
0.156–0.166, P < 0.001). Results of the different T
measurements correlated well with each other (Table 6). Correlations between serum levels of
T, E1, and E2 are shown in Table 7. E1 and E2 were
positively related with each other, and with the various measures of
T.
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Because BMI was significantly related to levels of T, maxLES, IGS, and BMD, all analyses including these parameters were done after adjustment for BMI.
All T measurements were positively related to TBBMD after adjustment
for age (Table 8). Calc-FT, non-SHBG-T,
the TT/SHBG ratio, and TT adjusted for SHBG were also significantly
positively related to all regions of proximal femur BMD. As an example,
the relationships between the different T measures and BMD of the
Ward’s triangle are shown in Table 8.
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All measurements for T were positively related with maxLES (Table 8)
and with IGS and after adjustment for age (with the exception that FT
was not related with IGS). T was independently related to both muscle
strength and BMD.
The SHBG-bound fraction of T was not related to any of the physical characteristics, with the exception of fat mass (ß = -1.03 ± 0.18, P < 0.001). The strength of the relations of the albumin-bound fraction of T to the physical characteristics was equal to those for non-SHBG-T.
Serum SHBG concentrations were inversely related to lean mass [ß = -0.07 ± 0.02 kg/(nmol/L), P < 0.001], fat mass [ß = -0.08 ± 0.02 kg/(nmol/L), P < 0.001], and BMD [e.g. TBBMD; ß = -0.001 ± 0.0003 (g/cm2)/(nmol/L), P = 0.01].
Relations between estrogens and physical characteristics
Serum E1 and E2 concentrations were not
related to muscle strength. In this elderly male population, serum
E1 levels were positively associated with TBBMD [ß
= 0.36 ± 0.12 (g/cm2)/(nmol/L), P =
0.004, age adjusted]. Serum E2 concentrations (total,
free, and non-SHBG bound) were positively related to TBBMD as well as
to hip BMD (Table 9). Serum
E1 contributed slightly more to the variation in TBBMD, as
shown by the Bs (respectively, 0.10 for E2 and 0.13 for
E1). To investigate whether the above described effect of T
on BMD might be mediated through its aromatization to estrogens, a
multiple regression analysis was performed, including BMD as the
dependent variable and E2 and T as the independent
variables. E2 and TT remained independently related to
TBBMD and contributed equally to the variation of TBBMD, as shown by
the Bs (both 0.11). Again, serum E1 contributed to a
slightly greater variation in TBBMD compared with TT (Bs, respectively,
0.12 and 0.10). Furthermore, with regard to hip BMD, E2 and
non-SHBG-T remained independently, significantly related to BMD.
Similar results were obtained when non-SHBG-E2 was the
independent variable.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Serum T concentrations as found in this study seem to be relatively low. Furthermore, calc-FT concentrations were significantly higher than measured FT. It has to be questioned whether the FT assay provides a good method to measure the biologically active fraction of circulating T. Our findings that FT (both measured and calculated), non-SHBG-T, and the TT/SHBG ratio decrease with increasing age are in agreement with previous studies (2, 21, 22). TT levels did not decrease with age, but TT levels in this population were below the normal range for middle-aged adults, suggesting that T levels had already declined in comparison with younger men. To our knowledge, no reference values for percentage of SHBG bound, albumin bound and free fractions of T exist in the elderly. The decrease of bioavailable T is probably due to the increase of SHBG-bound T with age, in combination with the decrease of the albumin-bound fraction to a similar extent.
Until recently, not much attention has been paid to the role of estrogens in elderly men. The studies that have been reported so far show no change of total E2 levels with age in men (23, 24, 25) or a decrease of E2 levels only at old age (26). In the present study, serum total E2 was inversely associated with age. Bioavailable and fE2 concentrations decreased with age to an even greater extent than total E2. Two earlier studies also reported a decrease of bioavailable E2 (12, 25). We studied, however, an older and larger population compared with these studies. As with T, the SHBG-bound fraction of serum E2 increased with age, whereas the albumin fraction decreased. In addition, serum E1 concentrations decreased with age.
A number of clinical problems prevalent in older men may be related to androgen deficiency, including reduced muscle strength (27, 28), changes in body composition, and loss of BMD (1, 3, 4). It should be of interest to know whether the decrease in bone mass with age is causally related with the decrease in lean mass and/or in serum T or E2 concentrations. Also, it would be important to investigate whether the fall in lean mass with age is caused by the decrease in muscle strength and/or serum T or E2 concentrations. Finally, also the reverse could be the case, in which the decrease in muscle strength with age is caused by the fall in lean mass, and/or serum T levels or other factors. Unfortunately, the cross-sectional nature of our study does not allow a differentiation between cause and effect. All the factors are statistically related, making it impossible to differentiate which factor explains another. Therefore, no conclusions can be drawn concerning the physiological pathway(s). For example, also physical activity per se might be a factor contributing to the relationships found. A longitudinal study is necessary to answer these questions. From the results of our study, we can, however, confirm previous findings that serum T was, independent of age, positively related to both IGS and maxLES. In addition, we found a positive, age-independent relation between estimates of serum T levels and bone density. Furthermore, in agreement with previous findings, T was inversely associated with fat mass, but not with lean body mass (1). Serum non-SHBG-bound T concentrations are not only related to TBBMD, but also to all regions of the proximal femur BMD.
In this study, we established whether free T, the non- SHBG-bound fraction of T, or TT measured in plasma represent the bioactive hormone best. Pardridge (13) suggested that albumin-bound T is available for uptake by most tissues, whereas SHBG-bound T is not. Considering the fact that non-SHBG-T as well as the albumin-bound fraction were strongly related to the physical characteristics of aging, it is possible that the albumin-bound fraction of T is available for uptake by tissues and can exert biological effects. Furthermore, in agreement with the suggestion of Pardridge (13), SHBG-bound T was not related to any physical characteristic. Serum non-SHBG-T concentrations were stronger related to the physical characteristics than TT, as shown by the Bs, and slightly stronger than serum calc-FT concentrations. In addition, non-SHBG-T levels were related to proximal femur BMD, whereas TT levels were not.
There was a considerable difference in the relationships between non-SHBG-bound T calculated according to the method described by Södergård et al. (14), and the TT/SHBG ratio as a measurement of non-SHBG-bound T, on the one hand, and the physical characteristics, on the other hand. The TT/SHBG ratio probably reflects in part the non-T-dependent inverse association of SHBG with these characteristics (demonstrated in the relation with lean mass, fat mass, and BMD). Furthermore, use of the ratio obfuscates the absolute levels of the components of the quotient. TT adjusted for SHBG as a measure of non-SHBG-bound T is probably a better parameter than TT/SHBG, because the inverse associations of SHBG are not taken into account. However, as judged by the Bs, it shows no clear advantage compared to non-SHBG-T. Thus, the calculated bioavailable T concentration, according the method described by Södergård et al. (14), seems to be an easy, inexpensive, and informative measure in representing the bioactive fraction of circulating T.
Most of the E2 and about 20% of E1 produced in normal men is formed by extraglandular aromatization of circulating androgens. A smaller part of the circulating E2 is derived from a direct secretion by the testicles (29). Most of the E1 in elderly men is produced by the adrenals. Recently it has been demonstrated that estrogens play an important role in maintaining BMD in healthy older men (5, 30). Trabecular bone is generally thought to be more responsive to gonadal steroids than cortical bone. However, we did not measure spinal BMD, because degenerative arthritis influences the outcome of measurements too strongly. In our population, serum total E2 was independent of age, strongly positively related to BMD at all sites measured. Serum non-SHBG-bound E2 was slightly stronger related to BMD at all sites measured compared with total E2, as shown by the Bs. This suggests that the non-SHBG-bound fraction of E2 is the best representation of bioactive hormone, although to a lesser extent than is the case for T, possibly because E2 is more dissociable from SHBG than T. These findings are in agreement with those described by Khosla et al. (12). Also serum E1 concentrations were related to bone density, although to TBBMD only. However, this relation was independent of E2 and T and contributed to an even greater extent to the variation in TBBMD than E2 or T levels. This might imply that E1 has an effect on BMD directly, or that it is locally converted to E2. Serum T and E2 both contribute equally to the variation in BMD, suggesting that the effect of T on bone is not only attributed to the aromatization to estrogens (31).
Although it is generally accepted that estrogens and fat mass, especially trunk fat, are strongly related in postmenopausal women (32), we did not find a significant relation between E1 or E2 and (trunk) fat mass in these elderly men, before or after adjustment for T. This confirms other findings that aromatase activity is also present in other tissues apart from fat (33, 34, 35, 36).
In summary, together with a decline in muscle strength, bone density, and body composition, bioavailable T, E1, total E2, and bioavailable E2 all decrease with age in healthy old men. In this cross-sectional study in healthy elderly men, non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T, which seems to play a direct role in the various physiological changes that occur during aging through its positive relation with muscle strength and BMD and its negative relation with fat mass. In addition, both serum estrone and estradiol seem to play a role in the age-related bone loss in elderly men, although the cross-sectional nature of this study precludes definitive conclusion. Non-SHBG-bound E2 seems to be the best parameter for serum levels of bioactive E2 in describing its positive relation with BMD.
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Acknowledgments |
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Footnotes |
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Received July 21, 1999.
Revised December 29, 1999.
Revised May 15, 2000.
Accepted June 5, 2000.
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References |
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J. Chen, M. R. Sowers, F. M. Moran, D. S. McConnell, N. A. Gee, G. A. Greendale, C. Whitehead, S. E. Kasim-Karakas, and B. L. Lasley Circulating Bioactive Androgens in Midlife Women J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4387 - 4394. [Abstract] [Full Text] [PDF]
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A. Tivesten, J. Hulthe, K. Wallenfeldt, J. Wikstrand, C. Ohlsson, and B. Fagerberg Circulating Estradiol Is an Independent Predictor of Progression of Carotid Artery Intima-Media Thickness in Middle-Aged Men J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4433 - 4437. [Abstract] [Full Text] [PDF]
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 E. Orwoll, L. C. Lambert, L. M. Marshall, J. Blank, E. Barrett-Connor, J. Cauley, K. Ensrud, S. R. Cummings, and for the Osteoporotic Fractures in Men Study Group Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med, October 23, 2006; 166(19): 2124 - 2131. [Abstract] [Full Text] [PDF]
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M. Muller, A. W. van den Beld, Y. T. van der Schouw, D. E. Grobbee, and S. W. J. Lamberts Effects of Dehydroepiandrosterone and Atamestane Supplementation on Frailty in Elderly Men J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3988 - 3991. [Abstract] [Full Text] [PDF]
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