| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Institute of Reproductive Medicine of the University, D-48129 Münster, Germany
Address all correspondence and requests for reprints to: Prof. E. Nieschlag, FRCP, Institute of Reproductive Medicine of the University, Domagkstr. 11, D-48129 Münster, Germany. E-mail: nieschl{at}uni-muenster.de.
Testosterone (T) substitution in hypogonadal men results in growth of the prostate gland. T effects are mediated via the androgen receptor (AR). The length of the (CAG)n polymorphism of the AR gene is negatively associated with transcriptional activity and might account for variations in prostate growth during substitution therapy. In 131 hypogonadal men aged 18–69 yr, we assessed prostate volume longitudinally by transrectal ultrasonography and determined AR (CAG)n, sex hormone levels, and anthropometric measures. Sixty-nine men with primary and 62 with secondary hypogonadism began substitution therapy with im injections of T enanthate (n = 81), transdermal T preparations (n = 19), sc injections of human chorionic gonadotropin (n = 17), or oral T undecanoate (n = 14) for 2.4 ± 0.8 yr. Average prostate size increased from 15.8 ± 6.1 ml to 23.0 ± 6.8 ml. ANOVA including covariates revealed initial prostate size to be dependent on age (P < 0.001) and baseline T levels (P = 0.01) but not on number of (CAG)n (ranging from 13–30; mean, 21.4 ± 3.5). Prostate growth per year and absolute prostate size under substituted T levels (6.1 ± 3.3 to 21.6 ± 10.3 nmol/liter) were strongly dependent on (CAG)n, with lower treatment effects in longer repeats (both P < 0.001). Other significant predictors were initial prostate size (negative for growth rate and positive for absolute size) and age (positive for both growth rate and absolute size). The odds ratio for men with (CAG)n less than 20, compared with those with (CAG)n of 20 or more to develop a prostate size of at least 30 ml under T substitution, was 8.7 (95% confidence interval, 3.1–24.3; P < 0.001). This observation was strongly age dependent with a more pronounced odds ratio in men older than 40 yr. This first pharmacogenetic study on androgen substitution in hypogonadal men demonstrates a marked influence of the AR gene (CAG)n polymorphism on prostate growth.
This work was supported by the Deutsche Forschungsgemeinschaft Confocal Research Group "The Male Gamete: Production, Maturation, Function."
Abbreviations: ANCOVA, Analysis of covariance; AR, androgen receptor; BPH, benign prostate hyperplasia; (CAG)n, CAG repeat; hCG, human chorionic gonadotropin; OR, odds ratio; PSA, prostate-specific antigen; T, testosterone.
This article has been cited by other articles:
 |
|
 |
|
  B. Kornmann, E. Nieschlag, M. Zitzmann, J. Gromoll, M. Simoni, and S. Von Eckardstein Body Fat Content and Testosterone Pharmacokinetics Determine Gonadotropin Suppression After Intramuscular Injections of Testosterone Preparations in Normal Men J Androl, September 1, 2009; 30(5): 602 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R D Stanworth, D Kapoor, K S Channer, and T H Jones Androgen receptor CAG repeat polymorphism is associated with serum testosterone levels, obesity and serum leptin in men with type 2 diabetes Eur. J. Endocrinol., December 1, 2008; 159(6): 739 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zitzmann and E. Nieschlag Androgen Receptor Gene CAG Repeat Length and Body Mass Index Modulate the Safety of Long-Term Intramuscular Testosterone Undecanoate Therapy in Hypogonadal Men J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3844 - 3853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Crabbe, V. Bogaert, D. De Bacquer, S. Goemaere, H. Zmierczak, and J. M. Kaufman Part of the Interindividual Variation in Serum Testosterone Levels in Healthy Men Reflects Differences in Androgen Sensitivity and Feedback Set Point: Contribution of the Androgen Receptor Polyglutamine Tract Polymorphism J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3604 - 3610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Borst, C. F. Conover, C. S. Carter, C. M. Gregory, E. Marzetti, C. Leeuwenburgh, K. Vandenborne, and T. J. Wronski Anabolic effects of testosterone are preserved during inhibition of 5{alpha}-reductase Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E507 - E514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zitzmann, S. Faber, and E. Nieschlag Association of Specific Symptoms and Metabolic Risks with Serum Testosterone in Older Men J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4335 - 4343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K Chandolia, C. M. Luetjens, J. Wistuba, C.-H. Yeung, E. Nieschlag, and M. Simoni Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus). Reproduction, August 1, 2006; 132(2): 355 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Zinn, P. Ramos, F. F. Elder, K. Kowal, C. Samango-Sprouse, and J. L. Ross Androgen Receptor CAGn Repeat Length Influences Phenotype of 47,XXY (Klinefelter) Syndrome J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5041 - 5046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zitzmann, M. Depenbusch, J. Gromoll, and E. Nieschlag X-Chromosome Inactivation Patterns and Androgen Receptor Functionality Influence Phenotype and Social Characteristics as Well as Pharmacogenetics of Testosterone Therapy in Klinefelter Patients J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6208 - 6217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Nieschlag, H.M. Behre, P. Bouchard, J.J. Corrales, T.H. Jones, G.K. Stalla, S.M. Webb, and F.C.W. Wu Testosterone replacement therapy: current trends and future directions Hum. Reprod. Update, September 1, 2004; 10(5): 409 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Heinlein and C. Chang Androgen Receptor in Prostate Cancer Endocr. Rev., April 1, 2004; 25(2): 276 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Field Fractures, Osteoporosis, and the Endocrinologist Arch Intern Med, December 8, 2003; 163(22): 2796 - 2796. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
