The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males

Zitzmann, Michael; Brune, Maik; Kornmann, Britta; Gromoll, Jörg; Junker, Ralf; Nieschlag, Eberhard

doi:10.1046/j.1365-2265.2001.01391.x

Cited by 107Bone health and osteoporosis researchHormonal and reproductive studiesSexual Differentiation and Disorders

The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males

Zitzmann, Michael, Brune, Maik, Kornmann, Britta, Gromoll, Jörg, Junker, Ralf, Nieschlag, Eberhard·2001·Clinical Endocrinology

DOI 10.1046/j.1365-2265.2001.01391.x

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Abstract

OBJECTIVE Bone metabolism and bone density (BD) are influenced by sex hormones. Testosterone (T) action is exerted through the androgen receptor (AR). We investigated the potential impact of the CAG repeat (CAGR) polymorphism within the AR gene on BD and bone metabolism in healthy younger males. PATIENTS AND MEASUREMENTS The number of CAGRs in 110 healthy men aged 20–50 years was determined by sequence analysis. We assessed BD by the radiation‐free method of quantitative ultrasound (QUS) of the phalanges. Serum levels of bone‐specific alkaline phosphatase (BAP) and urine secretion of free deoxypyridinoline (DPD, corrected for creatinine), serum levels of sex hormones, body fat content and lifestyle factors were determined. RESULTS In stepwise multiple regression models controlling for age, body fat content and lifestyle factors, the number of CAGRs was an independent negative predictor of BD (partial r = − 0·286, P = 0·001), whereas it was positively associated with markers of bone turnover (for BAP: partial r = 0·32, P = 0·001; for DPD: partial r = 0·241, P = 0·013). Levels of free T and oestradiol showed an independent and positive association with BD; age contributed significantly to lower BD. Age and free T were negatively associated with markers of bone turnover, whereas oestradiol showed a positive correlation with BAP and DPD. anova in groups according to age and the CAGR length suggested an increased age‐dependent bone loss in subjects with a CAGR length of 22–31 compared with 14–21 CAGRs (overall P < 0·01). CONCLUSIONS A high number of CAG repeats within the androgen receptor gene attenuates testosterone effects on bone density and bone metabolism. This seems to be associated with accelerated age‐dependent bone loss.

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Studies of CAG repeats and hypogonadal symptoms found findings similar to those in men with low testosterone, including depressed mood, anxiety, impaired spermatogenesis, and loss of bone mineral density.
“Results demonstrated findings similar to those observed in men with low T, including depressed mood, anxiety, impaired spermatogenesis, and loss of bone mineral density (BMD), among others.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [32]

A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum
Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6079 · Cited by 3,824 · see citing works
The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function
Chamberlain, N. L., Driver, E. D., & Miesfeld, R. L. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.15.3181 · Cited by 1,149 · see citing works
Estimation of total body water by bioelectrical impedance analysis
Kushner, R., & Schoeller, D. (1986) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/44.3.417 · Cited by 772 · see citing works
STUDIES ON BODY COMPOSITION
Pace, N., & Rathbun, E. N. (1945) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)51345-x · Cited by 757 · see citing works
Long-term effect of testosterone therapy on bone mineral density in hypogonadal men
Behre, H. M., Kliesch, S., Leifke, E., Link, T. M., & Nieschlag, E. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.8.4163 · Cited by 559 · see citing works
Self-citation
Effect of Testosterone Treatment on Bone Mineral Density in Men Over 65 Years of Age
Snyder, P. J. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.6.1966 · Cited by 460 · see citing works
Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.
Bellido, T., Jilka, R. L., Boyce, B. F., Girasole, G., Broxmeyer, H. E., Dalrymple, S. A., Murray, R., & Manolagas, S. C. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117995 · Cited by 429 · see citing works
Castrated Men Exhibit Bone Loss: Effect of Calcitonin Treatment on Biochemical Indices of Bone Remodeling*
Stepan, J. J., Lachman, M., ZVĚŘINA, J., Pacovský, V., & Baylink, D. J. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-69-3-523 · Cited by 423 · see citing works
Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China.
Hsing, A. W., Gao, Y., Wu, G., Wang, X., Deng, J., Chen, Y., Sesterhenn, I. A., Mostofi, F. K., Bénichou, J., & Chang, C. (2000) · PubMed · Cited by 311 · see citing works
Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines
Beilin, J., Ball, E., Favaloro, J., & Zajac, J. D. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0250085 · Cited by 265 · see citing works
Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length
Irvine, R. A. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.2.267 · Cited by 263 · see citing works
Single- and multifrequency models for bioelectrical impedance analysis of body water compartments
Gudivaka, R., Schoeller, D. A., Kushner, R. F., & Bolt, M. J. G. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.3.1087 · Cited by 261 · see citing works
Racial Variation in Prostate Cancer Incidence and in Hormonal System Markers Among Male Health Professionals
Platz, E. A. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.24.2009 · Cited by 252 · see citing works
The Linkage of Kennedy's Neuron Disease to ARA24, the First Identified Androgen Receptor Polyglutamine Region-associated Coactivator
Hsiao, P., Lin, D., Nakao, R., & Chang, C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20229 · Cited by 221 · see citing works
The Contribution of Testosterone to Skeletal Development and Maintenance: Lessons from the Androgen Insensitivity Syndrome
Marcus, R., Leary, D., Schneider, D. L., Shane, E. J., Favus, M. J., & Quigley, C. A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.3.6428 · Cited by 213 · see citing works
Estrogen Suppression in Males: Metabolic Effects1
Mauras, N., O'Brien, K. O., Klein, K. O., & Hayes, V. Y. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.7.6676 · Cited by 201 · see citing works
Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women
Becherini, L. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.13.2043 · Cited by 191 · see citing works
Androgen receptor gene CAG repeat length varies in a race-specific fashion in men without prostate cancer
Sartor, O. A., Zheng, Q., & Eastham, J. A. (1999) · Urology · doi:10.1016/s0090-4295(98)00481-6 · Cited by 160 · see citing works
Significance of Mutations in the Androgen Receptor Gene in Males with Idiopathic Infertility1
Hiort, O., Holterhus, P., Horter, T., Schulze, W., Kremke, B., Bals‐Pratsch, M., Sinnecker, G. H. G., & Kruse, K. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6713 · Cited by 159 · see citing works
Estrogen Receptor α Gene Polymorphisms and Bone Mineral Density: Haplotype Analysis in Women from the United Kingdom
Albagha, O., McGuigan, F. E., Reid, D. M., & Ralston, S. H. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.1.128 · Cited by 154 · see citing works
Mechanical Strain Stimulates Osteoblast Proliferation Through the Estrogen Receptor in Males as Well as Females
Damien, E., Price, J. S., & Lanyon, L. E. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.11.2169 · Cited by 153 · see citing works
Androgen Deficiency Induces High Turnover Osteopenia in Aged Male Rats: A Sequential Histomorphometric Study
Erben, R. G., Eberle, J., Stähr, K., & Goldberg, M. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.6.1085 · Cited by 152 · see citing works
Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men
Leifke, E., Korner, H., Link, T. M., Behre, H. M., Peters, P., & Nieschlag, E. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1380051 · Cited by 150 · see citing works
Self-citation
Estrogen Replacement Therapy in a Man with Congenital Aromatase Deficiency: Effects of Different Doses of Transdermal Estradiol on Bone Mineral Density and Hormonal Parameters
Rochira, V., Faustini‐Fustini, M., Antonio, B., & Carani, C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.5.6583 · Cited by 142 · see citing works
Phenotypic manifestations associated with CAG-repeat expansion in the androgen receptor gene in male patients and heterozygous females: a clinical and molecular study of 30 families
Mariotti, C., Castellotti, B., Pareyson, D., Testa, D., Eoli, M., Antozzi, C. G., Silani, V., Marconi, R., Tezzon, F., Siciliano, G., et al. (2000) · Neuromuscular Disorders · doi:10.1016/s0960-8966(99)00132-7 · Cited by 135 · see citing works
Genetic Markers, Bone Mineral Density, and Serum Osteocalcin Levels
Sowers, M. R., Willing, M. C., Burns, T. L., Deschenes, S. P., Hollis, B. W., Crutchfield, M., & Jannausch, M. L. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.8.1411 · Cited by 113 · see citing works
A TA Repeat Polymorphism in the Estrogen Receptor Gene Is Associated with Osteoporotic Fractures but Polymorphisms in the First Exon and Intron Are Not
Langdahl, B. L., Løkke, E., Carstens, M., Stenkjær, L. L., & Eriksen, E. F. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.11.2222 · Cited by 110 · see citing works
Estrogen Suppression in Males: Metabolic Effects
Mauras, N. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.7.2370 · Cited by 107 · see citing works
Altered Bone Mineral Density in Patients with Complete Androgen Insensitivity Syndrome
Bertelloni, S., Baroncelli, G. I., Federico, G., Cappa, M., Lala, R., & Saggese, G. (1998) · Hormone Research in Paediatrics · doi:10.1159/000023296 · Cited by 92 · see citing works
Effects of Androgens on the Insulin-Like Growth Factor System in an Androgen-Responsive Human Osteoblastic Cell Line
Gori, F., Hofbauer, L. C., Conover, C. A., & Khosla, S. (1999) · Endocrinology · doi:10.1210/endo.140.12.7213 · Cited by 85 · see citing works
Significance of Mutations in the Androgen Receptor Gene in Males with Idiopathic Infertility
Hiort, O. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.8.2810 · Cited by 60 · see citing works
Ultrasound Measurements at the Proximal Phalanges in Healthy Women and Patients with Hip Fractures
Alenfeld, F. E., Wüster, C. C., Funck, C., Pereira‐Lima, J. F. S., Fritz, T., Meeder, P. J., & Ziegler, R. (1998) · Osteoporosis International · doi:10.1007/s001980050081 · Cited by 49 · see citing works
Phalangeal US velocity discriminates between normal and vertebrally fractured subjects
Guglielmi, G., Cammisa, M., Serio, A., Scillitani, A., Chiodini, I., Carnevale, V., & Fusilli, S. (1999) · European Radiology · doi:10.1007/s003300050899 · Cited by 49 · see citing works
Longitudinal Evaluation of Perimenopausal Femoral Bone Loss: Effects of a Low-Dose Oral Contraceptive Preparation on Bone Mineral Density and Metabolism
Gambacciani, M., Ciaponi, M., Cappagli, B., Benussi, C., & Genazzani, A. R. (2000) · Osteoporosis International · doi:10.1007/s001980070099 · Cited by 47 · see citing works
PvuII Polymorphisms of the Estrogen Receptor α and Bone Mineral Density in Healthy Southern Chinese Women
Ho, A. Y. Y., Yeung, S. S. C., & Kung, A. W. C. (2000) · Calcified Tissue International · doi:10.1007/s002230010082 · Cited by 46 · see citing works
The relation between bone density, free androgen index, and estradiol in men 60 to 70 years old
Scopacasa, F., Horowitz, M., Wishart, J. M., Morris, H. A., Chatterton, B. E., & Need, A. G. (2000) · Bone · doi:10.1016/s8756-3282(00)00299-4 · Cited by 44 · see citing works
Quantitative ultrasonometry (QUS) for the evaluation of osteoporosis risk: Reference data for various measurement sites, limitations and application possibilities*
Wüster, C., Heilmann, P., Pereira-Lima, J., Schlegel, J., Anstätt, K., & Soballa, T. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1211986 · Cited by 43 · see citing works
Androgen receptor polymorphisms and mutations in male infertility
Yong, E., Lim, L. S., Wang, Q., Mifsud, A., Lim, J. L., Ong, Y. C., & Sim, K. S. (2000) · Journal of Endocrinological Investigation · doi:10.1007/bf03343778 · Cited by 43 · see citing works
Alleles of the Estrogen Receptor α-Gene and an Estrogen Receptor Cotranscriptional Activator Gene, Amplified in Breast Cancer-1 (AIB1), Are Associated with Quantitative Calcaneal Ultrasound
Patel, M. S., Cole, D. E. C., Smith, J. D., HAWKER, G. A., Wong, B. Y. L., Trang, H., Vieth, R., Meltzer, P. S., & Rubin, L. A. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.11.2231 · Cited by 38 · see citing works
Androgens and bone metabolism
Finkelstein, J. S. (1998) · Springer eBooks · doi:10.1007/978-3-642-72185-4_6 · Cited by 35 · see citing works
Quantitative Ultrasound of Phalanges and Dual-Energy X-ray Absorptiometry of Forearm and Hand in Patients with End-Stage Renal Failure Treated with Dialysis
Przedlacki, J., Pluskiewicz, W., Wieliczko, M., Drozdzowska, B., Matuszkiewicz‐Rowińska, J., Bogdańska-Straszyńska, B., Włodarczyk, D., & Ostrowski, K. (1999) · Osteoporosis International · doi:10.1007/s001980050186 · Cited by 34 · see citing works
Analysis of the CAG repeat region of the androgen receptor gene in a kindred with X-linked spinal and bulbar muscular atrophy
Belsham, D. D., Yee, W.-C., Greenberg, C. R., & Wrogemann, K. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90142-8 · Cited by 32 · see citing works
Effects of Orchidectomy on Bone Metabolism in Beagle Dogs.
Fukuda, S., & Iida, H. (2000) · Journal of Veterinary Medical Science · doi:10.1292/jvms.62.69 · Cited by 28 · see citing works
Sex steroids and bone metabolism: Comparison of in vitro effects of 17β-estradiol and testosterone on human osteosarcoma cell lines of various gender and differentiation
Fohr, B., Schulz, A., & Battmann, A. (2000) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2000-8400 · Cited by 26 · see citing works
Effects of long-term testosterone substitutive therapy on bone mineral content in men with hypergonadotrophic hypogonadism
Medraś, M., Jankowska, E. A., & Rogucka, E. (2001) · Andrologia · doi:10.1046/j.1439-0272.2001.00417.x · Cited by 18 · see citing works
Correlation of Quantitative Ultrasound of Bone with Biochemical Markers of Bone Resorption in Women with Osteoporotic Fractures
Fiore, C. E., Pennisi, P., Gibilaro, M., Fazzio, S. D., Impellizzieri, D., & Ramirez, M. G. (1999) · Journal of Clinical Densitometry · doi:10.1385/jcd:2:3:231 · Cited by 9 · see citing works
Quantitative ultrasound at the hand phalanges: comparison with quantitative computed tomography of the lumbar spine in postmenopausal women
Feltrin, G., Nardin, M., Marangon, A., Khadivi, Y., Calderone, M., & Conti, G. (2000) · European Radiology · doi:10.1007/s003300051013 · Cited by 8 · see citing works
Der Knochen und seine Erkrankungen – Teil II: Der Dialog zwischen Osteoblasten und Osteoklasten
Ziegler, R. (2009) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/s-0029-1234201 · Cited by 4 · see citing works
[Bone ultrasound and diagnosis of osteoporosis: correlation of 2 quantitative ultrasound methods with bone density].
Goerres, G. W., Altermatt, M., Müller‐Brand, J., Tyndall, A., & Theiler, R. (1998) · PubMed · Cited by 3 · see citing works
[Bone ultrasound and diagnosis of osteoporosis: correlation of 2 quantitative ultrasound methods with bone density].
Thurnheer, U. (1998) · PubMed · Cited by 2 · see citing works

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The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications
Kaufman, J. M., & Vermeulen, A. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0013 · Cited by 1,079 · see citing works
“As to the LH levels, which might be expected to vary according to differences in androgen sensitivity at the hypothalamic-pituitary level, there are no consistent findings with lack of association between AR CAG-repeat length and LH levels in some studies (140, 141), weak positive associations between repeat length an…”
BackgroundResult
Androgens and Cardiovascular Disease
Liu, P. Y., Death, A. K., & Handelsman, D. J. (2003) · Endocrine Reviews · doi:10.1210/er.2003-0005 · Cited by 690 · see citing works
“as well as bone (62) and sperm production (63) within the”
X-Chromosome Inactivation Patterns and Androgen Receptor Functionality Influence Phenotype and Social Characteristics as Well as Pharmacogenetics of Testosterone Therapy in Klinefelter Patients
Zitzmann, M., Depenbusch, M., Gromoll, J., & Nieschlag, E. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1424 · Cited by 231 · see citing works
“(18, 19); mood/cognition (20, 21); and sperm concentrations”
MethodSelf-citation
The CAG repeat polymorphism within the androgen receptor gene and maleness1
Zitzmann, M., & Nieschlag, E. (2003) · International Journal of Andrology · doi:10.1046/j.1365-2605.2003.00393.x · Cited by 228 · see citing works
Self-citation
Testosterone for the aging male; current evidence and recommended practice
Jones, H. (2008) · Clinical Interventions in Aging · doi:10.2147/cia.s190 · Cited by 204 · see citing works
“A receptor with a short CAG sequence produces greater activity when androgens attach, and men with shorter CAG polymorphisms exhibit androgenic traits, such as preserved bone density (Zitzmann et al 2001) and prostate growth during testosterone treatment (Zitzmann et al 2003).”
Androgen Receptor Gene CAG Repeat Polymorphism in the Development of Ovarian Hyperandrogenism
Ibáñez, L., Ong, K. K., Mongan, N. P., Jääskeläinen, J., Marcos, M. V., Hughes, I. A., de Zegher, F., & Dunger, D. B. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021791 · Cited by 179 · see citing works
The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men
Zitzmann, M., Gromoll, J., von Eckardstein, A., & Nieschlag, E. (2003) · Diabetologia · doi:10.1007/s00125-002-0980-9 · Cited by 173 · see citing works
“As clinical consequences, the number of CAGr was shown to be inversely associated with the risk of prostate cancer [27, 28, 31, 32, 33], benign prostatic hyperplasia [34, 35], sperm production [36, 37], bone density [38], endothelial function and HDL-cholesterol concentrations [39] as well as depression [40].”
BackgroundMethodResultSelf-citation
Phenotypic heterogeneity of mutations in androgen receptor gene
Rajender, S., Singh, L., & Kumarasamy Thangaraj, K. (2007) · Asian Journal of Andrology · doi:10.1111/j.1745-7262.2007.00250.x · Cited by 158 · see citing works
Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats
Huhtaniemi, I. T., Pye, S. R., Limer, K. L., Thomson, W., O’Neill, T. W., Platt, H., Payne, D., John, S., Jiang, M., Boonen, S., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0848 · Cited by 141 · see citing works
Testosterone treatment comes of age: new options for hypogonadal men
Nieschlag, E. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02618.x · Cited by 137 · see citing works
Self-citation
How Strong Is the Association Between CAG and GGN Repeat Length Polymorphisms in the Androgen Receptor Gene and Prostate Cancer Risk?
Zeegers, M. P., Kiemeney, L. A. L. M., Nieder, A. M., & D, H. O. M. (2004) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.1765.13.11 · Cited by 132 · see citing works
“Third, AR repeat polymorphisms have been shown to be associated with the incidence of other androgen-related clinical conditions; specifically, a high number of repeats seem to adversely influence fertility and spermatogenesis (60) and bone density (61), and fewer repeats are associated with increased risk of baldness…”
Background
Androgen Receptor CAGnRepeat Length Influences Phenotype of 47,XXY (Klinefelter) Syndrome
Zinn, A. R., Ramos, P., Elder, F. F. B., Kowal, K., Samango‐Sprouse, C. A., & ROSS, J. L. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0432 · Cited by 125 · see citing works
Voice in female‐to‐male transsexual persons after long‐term androgen therapy
Cosyns, M., Borsel, J. V., Wierckx, K., Dedecker, D., de Peer, F. V., Daelman, T., Laenen, S., & T'Sjoen, G. G. (2013) · The Laryngoscope · doi:10.1002/lary.24480 · Cited by 120 · see citing works
Salivary testosterone and a trinucleotide (CAG) length polymorphism in the androgen receptor gene predict amygdala reactivity in men
Manuck, S. B., Marsland, A. L., Flory, J. D., Gorka, A. X., Ferrell, R. E., & Hariri, A. R. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.04.013 · Cited by 114 · see citing works
“…1997; Zmuda et al., 1997; Choong and Wilson, 1998; Hsing et al., 2000; Ellis et al., 2001; Mifsud et al., 2001; Van Pottelbergh et al., 2001; Wallerand et al., 2001; Zitzmann et al., 2001a,b, 2002, 2003a,b; Van Golde et al., 2002; Walsh et al., 2005; Campbell et al., 2007; Lapauw et al., 2007).”
Diagnosis of hypogonadism in the aging male
Vermeulen, A., & Kaufman, J. (2002) · The Aging Male · doi:10.1080/tam.5.3.170.176 · Cited by 116 · see citing works
Prostate Volume and Growth in Testosterone-Substituted Hypogonadal Men Are Dependent on the CAG Repeat Polymorphism of the Androgen Receptor Gene: A Longitudinal Pharmacogenetic Study
Zitzmann, M., Depenbusch, M., Gromoll, J., & Nieschlag, E. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021947 · Cited by 112 · see citing works
“This refers to bone density (15), endothelial”
Self-citation
Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials
Trost, L. W., & Mulhall, J. P. (2016) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2016.04.068 · Cited by 98 · see citing works
Association of polymorphisms of the androgen receptor and klotho genes with bone mineral density in Japanese women
Yamada, Y., Ando, F., Niino, N., & Shimokata, H. (2004) · Journal of Molecular Medicine · doi:10.1007/s00109-004-0578-4 · Cited by 91 · see citing works
“Although the CAG repeat polymorphism of AR was shown to be associated with BMD in women or in men in some studies [11, 21, 22, 23, 24], other studies have failed to detect an effect of this polymorphism on BMD or fracture risk [25, 26].”
BackgroundResult
Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution
Zitzmann, M., Brune, M., & Nieschlag, E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020504 · Cited by 86 · see citing works
Self-citation
Intrinsic imperfections of endocrine replacement therapy
Romijn, J., Smit, J., & Lamberts, S. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1490091 · Cited by 85 · see citing works
“Presence of a high number of CAG repeats within the androgen receptor gene attenuates the effects of testosterone on bone density and bone metabolism ( 23 ), whereas a decreased number of CA repeats in the IGF-I gene is associated with a lower birth weight, lower body height and serum IGF-I concentrations at the lowes…”
Background
Androgen receptor CAG repeat polymorphism is associated with serum testosterone levels, obesity and serum leptin in men with type 2 diabetes
Stanworth, R. D., Kapoor, D., Channer, K. S., & Jones, T. H. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0266 · Cited by 84 · see citing works
“Shorter AR CAG are associated with prostate cancer (16, 17), benign prostatic hypertrophy (18, 19), prostate growth during testosterone treatment (20), semen parameters of fertility (21–23) and bone mineral density (24).”
Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action
Tirabassi, G., Cignarelli, A., Perrini, S., Muti, N. D., Furlani, G., Gallo, M., Pallotti, F., Paoli, D., Giorgino, F., Lombardo, F. P., et al. (2015) · International Journal of Endocrinology · doi:10.1155/2015/298107 · Cited by 81 · see citing works
“In healthy elderly men, the AR gene CAG repeat polymorphism was shown to have a neutral effect on the determination of bone turnover and bone mineral density [68].”
Background
Contribution of Gender‐Specific Genetic Factors to Osteoporosis Risk
Karasik, D., & Ferrari, S. (2008) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2008.00447.x · Cited by 79 · see citing works
“The few studies of the AR in men are not well-powered (Van Pottelbergh et al., 2001; Zitzmann et al., 2001), thus their results are inconclusive for male-specific associations.”
Result
Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification
Zhu, D., Hadoke, P. W. F., Wu, J., Vesey, A. T., Lerman, D. A., Dweck, M. R., Newby, D. E., Smith, L. B., & MacRae, V. E. (2016) · Scientific Reports · doi:10.1038/srep24807 · Cited by 79 · see citing works
Low free testosterone levels are associated with prevalence and incidence of depressive symptoms in older men
Joshi, D., Van Schoor, N. M., De Ronde, W., Schaap, L. A., Comijs, H. C., Beekman, A. T. F., & Lips, P. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03641.x · Cited by 78 · see citing works
The Role of the CAG Repeat Androgen Receptor Polymorphism in Andrology
Zitzmann, M. (2008) · Frontiers of hormone research · doi:10.1159/000175843 · Cited by 74 · see citing works
Self-citation
Aerobic exercise and bone mineral density in middle-aged finnish men: a controlled randomized trial with reference to androgen receptor, aromatase, and estrogen receptor α gene polymorphisms
Remes‐Pakarinen, T., Väisänen, S., Mahonen, A., Huuskonen, J., Kröger, H., Jurvelin, J. S., Penttilä, I., & Rauramaa, R. (2003) · Bone · doi:10.1016/s8756-3282(03)00032-2 · Cited by 74 · see citing works
“Furthermore, a high number of CAG repeats associates with the lower BMD in men [19] and women [20].”
BackgroundResultInfluential
Drug Insight: testosterone preparations
Srinivas-Shankar, U., & Wu, F. C. W. (2006) · Nature Clinical Practice Urology · doi:10.1038/ncpuro0650 · Cited by 72 · see citing works
“Thus, shorter CAG repeats are associated with higher androgenicity and longer CAG repeats with lower androgenicity”
Background
Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men
Aminorroaya, A., Kelleher, S., Conway, A. J., Ly, L. P., & Handelsman, D. J. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01920 · Cited by 68 · see citing works
Mechanisms of Disease: pharmacogenetics of testosterone therapy in hypogonadal men
Zitzmann, M. (2007) · Nature Clinical Practice Urology · doi:10.1038/ncpuro0706 · Cited by 67 · see citing works
Self-citation
Genotype and phenotype in Klinefelter syndrome - impact of androgen receptor polymorphism and skewed X inactivation
Bojesen, A., Hertz, J. M., & Gravholt, C. H. (2011) · International Journal of Andrology · doi:10.1111/j.1365-2605.2011.01223.x · Cited by 67 · see citing works
“Our study corroborates some of the findings by Zitzmann et al. (2004), especially the positive correlation Figure 3 A negative correlation in Klinefelter syndrome, between mean CAG repeat lengths and haematocrit, spearman’s q = )0.”
BackgroundResult
Osteoporosis in Klinefelter's syndrome
Ferlin, A., Schipilliti, M., Mambro, A. D., Vinanzi, C., & Foresta, C. (2010) · Molecular Human Reproduction · doi:10.1093/molehr/gaq026 · Cited by 67 · see citing works
“…outcome and response to testosterone therapy was found, with a statistically significant negative correlation between bone density evaluated by phalangeal ultrasound and the X-weighted biallelic mean of CAG repeats (Zitzmann et al., 2004), as previously shown in normal men (Zitzmann et al., 2001).”
Background
The Genetics of Bone Loss: Challenges and Prospects
Mitchell, B. D., & Yerges‐Armstrong, L. M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2865 · Cited by 61 · see citing works
“Associations have been reported between BMD and polymorphisms in the androgen receptor gene (AR) in some (75, 76), but not all, (77, 78) studies.”
Background
Current topics in testosterone replacement of hypogonadal men
Nieschlag, E. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.09.008 · Cited by 55 · see citing works
Self-citation
Role of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Polycystic Ovary Syndrome (PCOS)
Schüring, A. N., Welp, A., Gromoll, J., Zitzmann, M., Sonntag, B., Nieschlag, E., Greb, R. R., & Kiesel, L. (2011) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0031-1291343 · Cited by 53 · see citing works
Self-citation
The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes
Herbert, A. J., Williams, A. G., Hennis, P. J., Erskine, R. M., Sale, C., Day, S. H., & Stebbings, G. K. (2018) · European Journal of Applied Physiology · doi:10.1007/s00421-018-4007-8 · Cited by 53 · see citing works
Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics
Giwercman, A., Rylander, L., Rignell-Hydbom, A., Jönsson, B., Pedersen, H., Ludwicki, J., Lesovoy, V., Zvyezday, V., Spanô, M., Manicardi, G., et al. (2007) · Pharmacogenetics & Genomics · doi:10.1097/01.fpc.0000236329.26551.78 · Cited by 55 · see citing works
Polymorphisms in the CYP19 and AR Genes?Relation to Bone Mass and Longitudinal Bone Changes in Postmenopausal Women With or Without Hormone Replacement Therapy: The Danish Osteoporosis Prevention Study
Tofteng, C. L., Kindmark, A., Br�ndstr�m, H., Abrahamsen, B., Petersen, S., Stiger, F., Stilgren, L. S., Jensen, J. B., Vestergaard, P., Langdahl, B. L., et al. (2003) · Calcified Tissue International · doi:10.1007/s00223-002-2158-3 · Cited by 53 · see citing works
“In a study of young men, long repeats [(CAG)n>21] were associated with lower phalangeal BMD, higher bone turnover, and increased bone loss when comparing age groups [13].”
Background
Pharmacogenetics of Testosterone Replacement Therapy
Zitzmann, M. (2009) · Pharmacogenomics · doi:10.2217/pgs.09.58 · Cited by 49 · see citing works
Self-citation
CAG repeat length in the androgen receptor gene affects the risk of male infertility
Asatiani, K., von Eckardstein, S., Simoni, M., Gromoll, J., & Nieschlag, E. (2003) · International Journal of Andrology · doi:10.1046/j.1365-2605.2003.00420.x · Cited by 46 · see citing works
Self-citation
Monitoring bone density in hypogonadal men by quantitative phalangeal ultrasound
Zitzmann, M., Brune, M., Vieth, V., & Nieschlag, E. (2002) · Bone · doi:10.1016/s8756-3282(02)00831-1 · Cited by 41 · see citing works
Self-citation
Is the androgen receptor CAG repeat length significant for prostate cancer?
Giovannucci, E. L. (2002) · PubMed · Cited by 41 · see citing works
A CAG Repeat Polymorphism in the Androgen Receptor Gene is Associated with Reduced Bone Mass and Increased Risk of Osteoporotic Fractures
Carstens, M., Tofteng, C. L., Eriksen, E. F., Langdahl, B. L., & Stenkj�r, L. (2003) · Calcified Tissue International · doi:10.1007/s00223-002-0019-8 · Cited by 38 · see citing works
“demonstrated to be associated with reduced bone mass in both women and men [33, 34], however, other studies”
BackgroundResult
Association Between Androgen Receptor Gene CAG Repeat Polymorphism and Plasma Testosterone Levels in Postmenopausal Women
Brum, I. S., Spritzer, P. M., Paris, F., Maturana, M. A., Audran, F., & Sultan, C. (2005) · Journal of the Society for Gynecologic Investigation · doi:10.1016/j.jsgi.2004.11.003 · Cited by 37 · see citing works
CAG Repeat Testing of Androgen Receptor Polymorphism: Is This Necessary for the Best Clinical Management of Hypogonadism?
Francomano, D., Greco, E. A., Lenzi, A., & Aversa, A. (2013) · The Journal of Sexual Medicine · doi:10.1111/jsm.12268 · Cited by 34 · see citing works
Bone density and risk of osteoporosis in Klinefelter syndrome
Ferlin, A., Schipilliti, M., & Foresta, C. (2011) · Acta Paediatrica · doi:10.1111/j.1651-2227.2010.02138.x · Cited by 33 · see citing works
Androgen Receptor Gene CAG Repeat Polymorphism Regulates the Metabolic Effects of Testosterone Replacement Therapy in Male Postsurgical Hypogonadotropic Hypogonadism
Tirabassi, G., Muti, N. D., Corona, G., Maggi, M., & Balercia, G. (2013) · International Journal of Endocrinology · doi:10.1155/2013/816740 · Cited by 31 · see citing works
“Hindawi Publishing Corporation International Journal of Endocrinology Volume 2013, Article ID 816740, 7 pages http://dx.doi.org/10.1155/2013/816740”
BackgroundInfluential
Testosterone metabolism, dose–response relationships and receptor polymorphisms: selected pharmacological/toxicological considerations on benefits versus risks of testosterone therapy in men
Oettel, M. (2003) · The Aging Male · doi:10.1080/13685530312331309772 · Cited by 31 · see citing works
Steroid hormone receptor gene polymorphisms and osteoporosis: a pharmacogenomic review
Gennari, L., Paola, V. D., Merlotti, D., Martini, G., & Nuti, R. (2007) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.8.5.537 · Cited by 29 · see citing works
“Similar studies examining the association between these polymorphisms and BMD or fracture risk in different male and female populations yielded conflicting results [125-129].”
Result
Osteoporosis
Stock, H., Schneider, A. E., & Strauss, E. (2004) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000136842.75487.e2 · Cited by 29 · see citing works
“shows diminished action as the number of CAG repeat polymorphisms in exon 1 of the AR gene increases.(50,51)”
BackgroundInfluential
The androgen receptor CAG repeat polymorphism as a risk factor of low serum testosterone and its cardiometabolic effects in men
Haring, R., Ernst, F. D., Schurmann, C., Homuth, G., Völker, U., Völzke, H., Nauck, M. A., & Wallaschofski, H. (2011) · International Journal of Andrology · doi:10.1111/j.1365-2605.2011.01220.x · Cited by 27 · see citing works
“…parameters, based on small cross-sectional samples from selected or patient-based populations limiting their ability to detect a true relationship (Zitzmann et al., 2001a,b; Hersberger et al., 2005; Walsh et al., 2005; Stanworth et al., 2008, 2011; Guadalupe-Grau et al., 2010a,b; Nielsen et al.,…”
BackgroundMethodResultInfluential
The contributions of deficient androgen action in spermatogenic disorders
Ochsenkühn, R., & de Kretser, D. M. (2003) · International Journal of Andrology · doi:10.1046/j.1365-2605.2003.00381.x · Cited by 27 · see citing works
Gene polymorphisms involved in the regulation of bone quality
Thijssen, J. H. H. (2006) · Gynecological Endocrinology · doi:10.1080/09513590600629043 · Cited by 27 · see citing works
“The presence of long alleles has been related to low BMD in both sexes [120,121].”
Background
CAG Polymorphic Repeat Length in Androgen Receptor Gene Combined with Pretreatment Serum Testosterone Level as Prognostic Factor in Patients with Metastatic Prostate Cancer
Shimbo, M., Suzuki, H., Kamiya, N., Imamoto, T., Komiya, A., Ueda, T., Watanabe, M., Shiraishi, T., & Ichikawa, T. (2004) · European Urology · doi:10.1016/j.eururo.2004.10.016 · Cited by 26 · see citing works
The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: TIMES2 sub-study
Stanworth, R. D., Akhtar, S., Channer, K. S., & Jones, T. H. (2013) · European Journal of Endocrinology · doi:10.1530/eje-13-0703 · Cited by 25 · see citing works
Genetic Variation in Sex Hormone Genes Influences Heel Ultrasound Parameters in Middle-Aged and Elderly Men: Results From the European Male Aging Study (EMAS)
Limer, K. L., Pye, S. R., Thomson, W., Boonen, S., Borghs, H., Vanderschueren, D., Huhtaniemi, I. T., Adams, J. E., Ward, K. A., Platt, H., et al. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080912 · Cited by 24 · see citing works
“AR CAG repeat length has been tested for association with BMD in men in 10 studies; of these, two report longer repeat lengths associating with increased bone loss,((44,45)) and the other studies found no association.”
Background
The androgen receptor gene CAG repeat polymorphism does not predict increased risk of heart disease: longitudinal results from the Massachusetts Male Ageing Study
Page, S. T., Kupelian, V. A., Bremner, W. J., & McKinlay, J. B. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02598.x · Cited by 24 · see citing works
Bone Mass and the CAG and GGN Androgen Receptor Polymorphisms in Young Men
Guadalupe‐Grau, A., Rodríguez-González, F. G., Ponce‐González, J. G., Dorado, C., Olmedillas, H., Fuentes, T., Pérez‐Gómez, J., Sanchis‐Moysi, J., Díaz-Chico, B. N., & Calbet, J. A. L. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011529 · Cited by 23 · see citing works
“Additional studies carried out in elders showed no relationship between CAG repeat length and C-terminal telopeptide of the type I collagen, osteocalcin, BSAP and urinary deoxypirindoline [18,25].”
Background
The latest options and future agents for treating male hypogonadism
Edelstein, D. L., Sivanandy, M. S., Shahani, S., & Basaria, S. S. (2007) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.8.17.2991 · Cited by 23 · see citing works
“The finding that shorter CAG repeats are associated with higher androgenicity and longer CAG repeats with lower androgenicity has been seen in both hypogonadal and normal men [96-101] .”
Background
Association Between Repeat Length of Exon 1 CAG Microsatellite in the Androgen Receptor and Bone Density in Men is Modulated by Sex Hormone Levels
Stiger, F., Brändström, H., Gillberg, P., Melhus, H., Wolk, A., Michaëlsson, K., & Kindmark, A. (2008) · Calcified Tissue International · doi:10.1007/s00223-008-9128-3 · Cited by 23 · see citing works
Cardiovascular disease genetics: a long and winding road
Ordovás, J. M. (2003) · Current Opinion in Lipidology · doi:10.1097/00041433-200302000-00009 · Cited by 23 · see citing works
The complications of male hypogonadism: is it just a matter of low testosterone?
Munari, E. V., Amer, M., Amodeo, A., Bollino, R., Federici, S., Goggi, G., Giovanelli, L., Persani, L., Cangiano, B., & Bonomi, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1201313 · Cited by 22 · see citing works
Testosterone replacement therapy in male hypogonadism
Byrne, M. M., & Nieschlag, E. (2003) · Journal of Endocrinological Investigation · doi:10.1007/bf03345206 · Cited by 22 · see citing works
Self-citation
Age-related influence of common aromatase gene polymorphisms on bone mass of healthy men
Zarrabeitia, A., Zarrabeitia, M. T., Valero, C., González-Macı́as, J., & Riancho, J. A. (2004) · Bone · doi:10.1016/j.bone.2004.02.013 · Cited by 21 · see citing works
“[22] found a negative correlation between CAG repeat number and BMD in males of 20–50 years.”
Background
Androgen receptor polyglutamine repeat number: models of selection and disease susceptibility
Ryan, C. P., & Crespi, B. J. (2012) · Evolutionary Applications · doi:10.1111/j.1752-4571.2012.00275.x · Cited by 20 · see citing works
“In healthy men, AR CAGn is a negative predictor of BMD, and the effect of age on bone loss is greater in subjects with longer repeat length (22–31 repeats) compared to those with shorter repeat lengths (14 –21 repeats; Zitzmann et al. 2001b).”
BackgroundInfluential
Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism
Tirabassi, G., Muti, N. D., Gioia, A., Biagioli, A., Lenzi, A., & Balercia, G. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0052-2 · Cited by 20 · see citing works
“Accordingly, data in the literature show that TRT is particularly effective in those patients with a marked baseline deficit of bone density [20].”
Lack of Association Between Androgen Receptor Polymorphisms and Bone Mineral Density or Physical Function in Older Men
Kenny, R. A., McGee, D., Joseph, C. M., Covault, J., Abreu, C., & Raisz, L. G. (2005) · Endocrine Research · doi:10.1080/07435800500406221 · Cited by 20 · see citing works
The relation of the Xbal and Pvull polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene to peak bone mass and bone turnover rate among young healthy men
Välimäki, V., Piippo, K., Välimäki, S., Löyttyniemi, E., KONTULA, K. K., & Välimäki, M. J. (2005) · Osteoporosis International · doi:10.1007/s00198-005-1889-1 · Cited by 19 · see citing works
“Consequently, the finding of the number of CAG repeats as a negative indicator of bone density in men aged 20 to 50 years might imply that the CAG polymorphism determines the development of peak bone mass in men [28].”
Background
Osteoporosis and Low Bone Mineral Density in Men with Testosterone Deficiency Syndrome
Gaffney, C., Pagano, M. J., Kuker, A. P., Stember, D. S., & Stahl, P. J. (2015) · Sexual Medicine Reviews · doi:10.1002/smrj.63 · Cited by 18 · see citing works
CAG Repeat Polymorphism in the Androgen Receptor Gene in Women with Rheumatoid Arthritis
Dziedziejko, V., Kurzawski, M., Safranow, K., Ossowski, A., PIATEK, J., Parafiniuk, M., Chlubek, D., & Pawlik, A. (2011) · The Journal of Rheumatology · doi:10.3899/jrheum.110894 · Cited by 16 · see citing works
Endobiogeny: A Global Approach to Systems Biology (Part 2 of 2)
Lapraz, J.-C., Hedayat, K. M., & Pauly, P. (2013) · Global Advances in Health and Medicine · doi:10.7453/gahmj.2013.013 · Cited by 16 · see citing works
Bone benefits of testosterone replacement therapy in male hypogonadism.
Tirabassi, G., Biagioli, A., & Balercia, G. (2014) · PubMed · Cited by 15 · see citing works
Androgen receptor CAG repeat polymorphism and hypothalamic‐pituitary‐gonadal function in Filipino young adult males
Ryan, C. P., McDade, T. W., Gettler, L. T., Eisenberg, D. T. A., Rzhetskaya, M., Hayes, M. G., & Kuzawa, C. W. (2016) · American Journal of Human Biology · doi:10.1002/ajhb.22897 · Cited by 15 · see citing works
“…hypogonadism or other kinds American Journal of Human Biology 2017;29:e22897. https://doi.org/10.1002/ajhb.22897 wileyonlinelibrary.com/journal/ajhb VC 2016 Wiley Periodicals, Inc. | 1 of 9 of androgen insensitivity (Nieschlag, Behre, & Nieschlag, 2004; Walsh et al., 2005; Zitzmann et al., 2001).”
BackgroundInfluential
Androgen Receptor CAG Repeat Size is Associated with Stress Fracture Risk: A Pilot Study
Yanovich, R., Milgrom, R., Friedman, E., & Moran, D. S. (2011) · Clinical Orthopaedics and Related Research · doi:10.1007/s11999-011-1805-2 · Cited by 14 · see citing works
“[43] reported a similar relationship between BMD and CAG repeat size in men, whereby men with longer CAG repeat sizes (range, 22–31) had lower BMD and age-dependent bone loss than men with repeat sizes in the 14 to 21 range.”
Background
Polymorphisms in androgen and estrogen receptor genes: effects on male aging
Jiang, M., & Huhtaniemi, I. T. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.06.017 · Cited by 14 · see citing works
Testosterone Substitution: Current Modalities and Perspectives
Zitzmann, M., & Nieschlag, E. (2006) · Journal für Kardiologie (Krause & Pachernegg GmbH) · Cited by 12 · see citing works
Self-citation
[Physiology of androgens in adult men].
Tostain, J.-B., Rossi, D., & Martin, P. (2004) · PubMed · Cited by 12 · see citing works
Molecular psychogenetics of deviant aggressive behavior in humans
Vasilyev, V. A. (2011) · Russian Journal of Genetics · doi:10.1134/s1022795411080163 · Cited by 11 · see citing works
“The majority of researchers believe that the blood test osterone level in males is independent the length of the CAG microsatellite cluster [86], but the CAG repeat number proved to correlate with clinical manifesta tions of androgen dependent reactions [87].”
Background
The androgen receptor gene CAG repeat in relation to 4-year changes in androgen-sensitive endpoints in community-dwelling older European men
Eendebak, R. J. A. H., Huhtaniemi, I. T., Pye, S. R., Ahern, T., O’Neill, T. W., Bártfai, G., Casanueva, F. F., Maggi, M., Forti, G., Alston, R. D., et al. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0447 · Cited by 10 · see citing works
Androgen receptor CAG repeat length as a moderator of the relationship between free testosterone levels and cognition
Tan, S., Porter, T., Bucks, R. S., Weinborn, M., Milicic, L., Brown, A., Rainey‐Smith, S. R., Taddei, K., Ames, D. J., Masters, C. L., et al. (2021) · Hormones and Behavior · doi:10.1016/j.yhbeh.2021.104966 · Cited by 10 · see citing works
A Rationale for the Use of Testosterone “Salvage” in Treatment of Men With Erectile Dysfunction Failing Phosphodiesterase Inhibitors
Aversa, A., Bruzziches, R., & Spera, G. (2005) · The Endocrinologist · doi:10.1097/01.ten.0000157887.08246.5a · Cited by 9 · see citing works
Analysis of diurnal variation in serum testosterone levels in men with symptoms of testosterone deficiency
Novaes, L. F., Flores, J. M., Benfante, N. E., Schofield, E., Katz, D. J., Nelson, C. J., & Mulhall, J. P. (2024) · The Journal of Sexual Medicine · doi:10.1093/jsxmed/qdae026 · Cited by 8 · see citing works
CAG polymorphism of the androgen receptor gene in azoospermic and oligozoospermic men from Ukraine
Фесай, О. А., Kravchenko, S. A., Tyrkus, M., Makuh, G. W., Zinchenko, V. M., Strelko, G. V., & Лившиц, Л. А. (2009) · Cytology and Genetics · doi:10.3103/s0095452709060061 · Cited by 7 · see citing works
“This causes a high degree of association in the hormonereceptor complex, leading to transcription activation [13].”
Background
Pathophysiology of the androgen receptor
Hiort, O., Werner, R., & Zitzmann, M. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9781139003353.004 · Cited by 7 · see citing works
Self-citation
Hearts and bones
Qi, L., Shen, H., & Ordovás, J. M. (2003) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/s0939-4753(03)80176-x · Cited by 7 · see citing works
Aging in the Hypothalamic-Pituitary-Testicular Axis
Handelsman, D. J. (2006) · Elsevier eBooks · doi:10.1016/b978-012515400-0/50054-3 · Cited by 6 · see citing works
A new approach to biological modeling: Introduction to the biology of functions
Hedayat, K. M., & Lapraz, J.-C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816903-2.00015-x · Cited by 5 · see citing works
Sex Hormones and Immunosenescence
Gómez, C. R., Nomellini, V., & Kovacs, E. J. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_42 · Cited by 4 · see citing works
Androgens in male senescence
Kaufman, J., T'Sjoen, G. G., & Vermeulen, A. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9781139003353.017 · Cited by 3 · see citing works
Polymorphisms and Male Ageing
Jiang, M., & Huhtaniemi, I. T. (2004) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-662-07019-2_5 · Cited by 3 · see citing works
Molecular genetic polymorphism of androgen receptor gene (AR) in African populations of Hadza and Datoga
Shibalev, D. V., Васильев, В. А., Лазебный, О. Е., Suchodolskaya, E. M., Куликов, А. М., Dronova, D. A., Butovskaya, M., & Рысков, А. П. (2013) · Russian Journal of Genetics · doi:10.1134/s1022795413120119 · Cited by 2 · see citing works
“However, it was demonstrated that the number of CAG repeats correlated with clinical manifestation of androgen dependent reactions [4].”
Background
Osteoporosis
Vigorita, V. J. (2006) · Techniques in Foot & Ankle Surgery · doi:10.1097/01.btf.0000247179.93072.2a · Cited by 1 · see citing works
“For example, the CAG repeat polymorphism (CAGR) in the androgen receptor gene has been associated with decreased bone mineral density and the increased incidence of vertebral fractures in males.(4)”
Background
Physiopathologie du déficit androgénique lié à l'âge
Shakespeare, W. (2004) · Cited by 1 · see citing works
[Occurrence of androgen receptor gene CAG trinucleotide sequence polymorphism in the metropolitan population of Polish men].
Filus, A., Medraś, M., Kuliczkowska-Płaksej, J., Trzmiel-Bira, A., Łaczmański, Ł., & Jędrzejuk, D. (2009) · PubMed · Cited by 1 · see citing works
Influence of androgen receptor on bone health in transgender adults: insights from the COMET study
Ceolin, C., Scala, A., Rocca, M. S., Scagnet, B., Marton, M., Simonato, C., Ziliotto, C., RUI, M. D., Camozzi, V., Giannini, S., et al. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-024-02522-z · Cited by 1 · see citing works
“In certain studies, longer CAG repeats have been demonstrated to be linked with decreased bone mass in both cisgender women and men [27, 29, 30].”
Treatment of Hypogonadism in Men
Mehta, A., Paduch, D. A., & Goldstein, M. (2012) · Springer eBooks · doi:10.1007/978-1-4471-4405-2_5 · Cited by 1 · see citing works
Genetic causes of sex differentiation abnormalities in males with normal testosterone level: role of androgen receptors
Kazakov, R. E., Rozhivanov, R. V., & Ших, Е. В. (2019) · Andrology and Genital Surgery · doi:10.17650/2070-9781-2019-20-1-13-21 · Cited by 1 · see citing works
CAG Repeat Polymorphism in Relation to Bone Mass, Metabolism, and Fractures
Joseph, C., & Kenny, A. M. (2005) · The Endocrinologist · doi:10.1097/01.ten.0000152724.77172.7b · Cited by 1 · see citing works
Giornale Italiano di MEDICINA SESSUALE e RIPRODUTTIVA
Pescatori, E. S., Gentile, V., Franco, G., Farina, F. P., & Salonia, A. (2007) · Cited by 1 · see citing works
Osteoporosi maschile: il ruolo degli estrogeni
Madeo, B., Rochira, V., & Carani, C. (2009) · L Endocrinologo · doi:10.1007/bf03344641

Association Between Repeat Length of Exon 1 CAG Microsatellite in the Androgen Receptor and Bone Density in Men is Modulated by Sex Hormone Levels
Stiger, F., Brändström, H., Gillberg, P., Melhus, H., Wolk, A., Michaëlsson, K., & Kindmark, A. (2008) · Calcified Tissue International · doi:10.1007/s00223-008-9128-3 · Cited by 23 · see citing works
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Pottelbergh, I. V., Lumbroso, S., Goemaere, S., Sultan, C., & Kaufman, J. (2001) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2001.01403.x · Cited by 95 · see citing works
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Hussein, Z., Ellis, J. A., LaMantia, A., Greenland, K. J., Yeung, S., Wong, Z. W., Zajac, Z., Harrap, S. B., & Ebeling, P. R. (2003) · Bone
Bone Mass and the CAG and GGN Androgen Receptor Polymorphisms in Young Men
Guadalupe‐Grau, A., Rodríguez-González, F. G., Ponce‐González, J. G., Dorado, C., Olmedillas, H., Fuentes, T., Pérez‐Gómez, J., Sanchis‐Moysi, J., Díaz-Chico, B. N., & Calbet, J. A. L. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011529 · Cited by 23 · see citing works
The (CAG)n repeat polymorphism of the androgen receptor gene is associated with bone mineral density in menopausal women
Markatseli, A. E., Lazaros, L. A., Kostoulas, H., Markoula, S., Tigas, S. K., Georgiou, I. A., & Tsatsoulis, A. A. (2015) · Endocrine Abstracts · doi:10.1530/endoabs.37.gp.10.06

Authors: Zitzmann, M., Brune, M., Kornmann, B., Gromoll, J., Junker, R., & Nieschlag, E.
Affiliations: University of Münster (DE)
ORCID: Zitzmann, Michael
Gromoll, Jörg
Nieschlag, Eberhard
Venue: Clinical Endocrinology
Publisher: Wiley
Published: 2001-11
Volume: 55
Issue: 5
Pages: 649-657
ISSN: 0300-0664 (ISSN-L)
1365-2265
DOI: 10.1046/j.1365-2265.2001.01391.x
OpenAlex: W2017076191
Cited by: 107
References: 51
Citations by year: 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 4
FWCI: 9.61
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2603 d)
Locations: Clinical Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords: androgen receptor gene, CAG repeat polymorphism, bone mineral density, bone metabolism, bone turnover markers, bone-specific alkaline phosphatase, deoxypyridinoline, testosterone, estradiol, age-related bone loss, healthy young men
MeSH terms: Adult, Aging, Alkaline Phosphatase, Amino Acids, Analysis of Variance, Body Constitution, Bone and Bones, Estradiol, Humans, Male, Middle Aged, Polymorphism, Genetic, Receptors, Androgen, Sex Hormone-Binding Globulin, Testosterone, Biomarkers, Bone Density, Trinucleotide Repeats

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The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males

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