Androgen Replacement Therapy

Wang, Christina; Swerdloff, Ronald S.

doi:10.3109/07853899708999363

Cited by 38 publications

(21 citation statements)

References 16 publications

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“…Androgen deficiency in men leads to a significant decrease in bone mineral density (BMD) [2], which can be improved by testosterone supplementation [3][4][5][6][7][8][9]. Although it is known that BMD may be decreased in patients with KS, data on the effect of androgen treatment on BMD in KS are limited and contradictory [3,[9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Bone Mineral Density and Quantitative Ultrasound Parameters in Patients with Klinefelter's Syndrome after Long-Term Testosterone Substitution

Bergh¹,

Hermus²,

Spruyt³

et al. 2001

Osteoporosis International

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Klinefelter's syndrome (KS) is a common sex chromosomal disorder associated with androgen deficiency and osteoporosis. Only few bone mineral density (BMD) and no quantitative ultrasound (QUS) data are available in these patients after long-term testosterone replacement therapy. We examined in a cross-sectional study 52 chromatin-positive KS patients aged 39.1 +/- 12.4 years (mean +/- SD). Patients had been treated with oral or parenteral androgens for 9.2 +/- 8.2 years (range 1-32 years). Areal BMD and bone mineral apparent density (BMAD, i.e., estimated volumetric BMD) at the lumbar spine, total hip and femoral neck were determined by dual-energy X-ray absorptiometry. BMD T-scores in the patient group were calculated based on three different North American reference databases. The QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus using an ultrasound imaging device (UBIS 3000) and were compared with QUS results in a sex-, age- and height-matched control group. QUS T-scores were calculated based on the results of QUS measurements in 50 normal Dutch men between the ages of 20 and 30 years. QUS and BMD results in the KS patient group were compared. Overall, based on the three reference databases, 46% and 63% of the KS patients had a T-score between -1 and -2.5 and a further 10% and 14% had a T-score < or = -2.5 at the total hip and/or lumbar spine, as measured by areal BMD or BMAD, respectively. Thirty-nine percent of the KS patients had a T-score between -2.5 and -1, while 2% had a T-score < or = -2.5 for BUA and/or SOS. BUA (77.7 +/- 15.0 dB/MHz) and SOS (1518.8 +/- 36.5 m/s) were significantly lower in the KS patients than in age- and height-matched controls (87.1 +/- 17.8 dB/MHz, p < 0.005, and 1536.5 +/- 42.5 m/s, p < 0.05). Correlation coefficients between the QUS parameters and areal BMD (0.28 to 0.37) or BMAD (0.27 to 0.46) were modest. ROC analysis showed that discrimination of a BMD or BMAD T-score < or = -2.5 with either BUA or SOS was not statistically significant. Although a limitation of our study is that direct comparison of BMD and QUS T-scores is not possible because in the control group in which QUS parameters were determined no BMD measurements were performed, we conclude that despite long-term testosterone replacement therapy, a considerable percentage of patients with KS had a BMD T-score < -1 or even < or = -2.5, based on different North American reference databases. This percentage was even higher for BMAD. QUS parameters were also low in the KS patient group when compared with Dutch control subjects. QUS parameters cannot be used to predict BMD or BMAD in KS patients.

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Section: Introductionmentioning

confidence: 99%

Bone Mineral Density and Quantitative Ultrasound Parameters in Patients with Klinefelter's Syndrome after Long-Term Testosterone Substitution

Bergh¹,

Hermus²,

Spruyt³

et al. 2001

Osteoporosis International

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“…Testosterone, the main male sex hormone, is one of the structurally similar steroid hormones. Measurement of serum testosterone levels is important in the evaluation of conditions associated with hyperandrogenism in women (1,2) and to diagnose hypogonadism, impotence, and problems in spermatogenesis and pubertical development in men (3,4). Development of monoclonal antibodies that would fulfill the high affinity and selectivity requirements needed for the accurate measurement of testosterone levels in serum samples has not been successful with the use of hybridoma technology.…”

mentioning

confidence: 99%

Structural Insights into Steroid Hormone Binding

Valjakka¹,

Takkinenz²,

Teerinen³

et al. 2002

Journal of Biological Chemistry

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The monoclonal anti-testosterone antibody (3-C 4 F 5 ) has a relatively high affinity (3 ؋ 10 8 M ؊1 ) with an overall good specificity profile. However, the earlier characterized binding properties have shown that both the affinity and specificity of this antibody must be improved if it is intended for use in clinical immunoassays. In this paper, the crystal structures of the recombinant antitestosterone (3-C 4 F 5 ) Fab fragment have been determined in the testosterone-bound and free form at resolutions of 2.60 and 2.72 Å, respectively. The high affinity binding of the (3-C 4 F 5 ) Fab is mainly determined by shape complementarity between the protein and testosterone. Only one direct hydrogen bond is formed between the hydroxyl group of the testosterone D-ring and the main-chain oxygen of Gly100 J H. The testosterone is deeply bound in a hydrophobic pocket, and the close shape complementarity is mainly formed by the third complementarity-determining regions ( The number of different, closely related steroid hormones in human serum is high, and their relative concentrations, which usually are very low, can vary greatly even between normal healthy individuals. Testosterone, the main male sex hormone, is one of the structurally similar steroid hormones. Measurement of serum testosterone levels is important in the evaluation of conditions associated with hyperandrogenism in women (1, 2) and to diagnose hypogonadism, impotence, and problems in spermatogenesis and pubertical development in men (3, 4). Development of monoclonal antibodies that would fulfill the high affinity and selectivity requirements needed for the accurate measurement of testosterone levels in serum samples has not been successful with the use of hybridoma technology. Rabbit polyclonal antibodies are used in most current immunoassays of steroid hormones. However, the supply of polyclonal reagents with consistent quality is a severe problem for the immunodiagnostic industry and requires continuous immunization of many animals. The inherent batch-to-batch variation of the polyclonal sera makes it necessary to optimize the assay parameters for each new serum batch.The three-dimensional structures of steroid binding Fab fragments are important for a general understanding of the molecular basis of specific interactions between antibodies and hydrophobic molecules such as steroids. The molecular basis of steroid antibody interactions has been studied in detail by determining the structures of a progesteronebinding antibody (DB3) in its free and bound form and with different high affinity cross-reactive progesterone derivatives (5-7). The binding site of the DB3 antibody is a hydrophobic pocket, and the binding affinity and specificity are determined by van der Waals interactions and a few hydrogen bonds formed with the progesterone hapten (5). The high affinity binding mode of a number of progesterone derivatives is due to two alternate docking orientations for the steroid skeleton (6). In the cases of the anti-digoxin 26-10 and 40-50 antibodies, the h...

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“…As to why peripheral muscle mass distribution associated with serum testosterone levels, it is well known that androgens have been used to increase muscle size and strength [17][18][19][20]. Testosterone increases muscle fibers.…”

Section: Discussionmentioning

confidence: 99%

Relationships among Serum Testosterone Levels, Body Fat and Muscle Mass Distribution in Women with Polycystic Ovary Syndrome.

2001

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Abstract.We investigated the relationships among serum testosterone levels, body fat and muscle mass distribution in women with polycystic ovary syndrome (PCOS).Subjects were 67 women with PCOS (mean age±standard deviation, 28.8±6.6 years). Baseline characteristics included age and height. Trunk-leg fat ratio and trunk-leg muscle ratio were assessed with dual-energy x-ray absorptiometry.Serum testosterone and dehydroepiandrosterone sulfate levels were measured with radioimmunoassays. Relationships among serum testosterone levels, body fat and muscle mass distribution were investigated using Pearson and partial correlation tests. Serum testosterone levels were positively correlated with trunk-leg fat ratio (r=0.398, P<0.01), but were inversely correlated with trunk-leg muscle ratio (r= -0.332, P<0.05).Trunk-leg muscle ratio was inversely correlated with trunk-leg fat ratio (r= -0.360, P<0.01).Serum testosterone levels were still correlated with trunk-leg fat ratio (r=0.500, P<0.001) and trunk-leg muscle ratio (r= -0.286, P <0.05), after adjusting for age and height. Trunk-leg fat ratio was still correlated with trunk-leg muscle ratio, after adjusting for age, height, and serum testosterone levels. Based on these results, we concluded that higher serum testosterone levels may contribute to the upper body fat distribution and peripheral muscle mass distribution.In addition, peripheral muscle mass distribution may also contribute to the upper body fat distribution.

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Androgen Replacement Therapy

Cited by 38 publications

References 16 publications

Bone Mineral Density and Quantitative Ultrasound Parameters in Patients with Klinefelter's Syndrome after Long-Term Testosterone Substitution

Bone Mineral Density and Quantitative Ultrasound Parameters in Patients with Klinefelter's Syndrome after Long-Term Testosterone Substitution

Structural Insights into Steroid Hormone Binding

Relationships among Serum Testosterone Levels, Body Fat and Muscle Mass Distribution in Women with Polycystic Ovary Syndrome.

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