Category Archives: Testosterone

Testosterone treatment after prostate cancer

Source

Department of Urology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
Abstract

PURPOSE:

A history of prostate cancer has been an absolute contraindication for testosterone supplementation. We studied a cohort of hypogonadal patients treated with radical retropubic prostatectomy (RRP) for organ confined prostate cancer to determine if testosterone replacement therapy (TRT) could be efficacious and administered safely without causing recurrent prostate tumor.
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Low testosterone predicts increased mortality and testosterone replacement therapy improves survival in men with type 2 diabetes

Barnsley Hospital NHS Foundation Trust, Barnley, UK; 2University of Sheffield, Sheffield, UK.
Background: Low testosterone in men is associated with increase in all-cause and cardiovascular mortality. There is a high prevalence of hypogonadism in men with type 2 diabetes and testosterone replacement therap) (TRT) improves cardiovascular risk. However there is no published data regarding mortality in these patients in relation to testosterone levels, and the long term effect of TRT on mortality.

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Low Testosterone Levels Linked to Increased Male Mortality CME/CE

News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD, FAAFP

Disclosures

To earn CME credit, read the news brief along with the CME information that follows and answer the test questions.

Release Date: August 28, 2006Valid for credit through August 28, 2007

Physicians – maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians – up to 0.25 AAFP Prescribed credit(s) for physicians;
Nurses – 0.3 nursing contact hours (None of these credits is in the area of pharmacology)
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Testosterone therapy increases sex drive of postmenopausal women

Testosterone therapy is an effective treatment for low libido in postmenopausal women, suggest results of an international study of more than 800 women.

Previous research has shown that testosterone therapy is useful for restoring libido in women when used in conjunction with estrogen replacement therapy. However, this study is the first to show that testosterone by itself can enhance sexual wellbeing in postmenopausal women.
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Canadian Society for the Study of the Aging Male: response to health Canada’s position paper on testosterone treatment.

Bain J, Brock G, Kuzmarov I; International Consulting Group.
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Progression of Atherosclosis in Menopausal Women not on Hormones

The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 1 131-138
Copyright © 2008 by The Endocrine Society
Relationship between Serum Levels of Sex Hormones and Progression of Subclinical Atherosclerosis in Postmenopausal Women
Roksana Karim, Howard N. Hodis, Frank Z. Stanczyk, Rogerio A. Lobo and Wendy J. Mack

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Endogenous testosterone and mortality

Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study.
Circulation. 2007 Dec 4;116(23):2694-701. Epub 2007 Nov 26. Links

Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N.

Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. kk101@medschl. cam.ac.uk

BACKGROUND: The relation between endogenous testosterone concentrations and health in men is controversial. METHODS AND RESULTS: We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone ( approximately 1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years. CONCLUSIONS: In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease. PMID: 18040028 [PubMed - in process]

Testosterone Supplementation Therapy for Older Men: Potential Benefits and Risks

Journal of the American Geriatrics Society
Volume 51 Issue 1 Page 101-115, January 2003
To cite this article: David A. Gruenewald MD, Alvin M. Matsumoto MD (2003)

Journal of the American Geriatrics Society 51 (1), 101–115.
doi:10.1034/j.1601-5215.2002.51018.x
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Abstract
Testosterone Supplementation Therapy for Older Men: Potential Benefits and Risks

  • David A. Gruenewald, MD*†‡, and
  • Alvin M. Matsumoto, MD*†‡
  • *Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, and †Division of Gerontology and Geriatric Medicine, Department of Medicine, and ‡Population Center for Research in Reproduction, University of Washington School of Medicine, Seattle, Washington.

Address correspondence to David A. Gruenewald, MD, Veterans Affairs Puget Sound Health Care System, S-182-GRECC, 1660 South Columbian Way, Seattle, WA 98108. E-mail: david.gruenewald@med.va.gov.

Abstract

Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded.

In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased.

Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials. J Am Geriatr Soc 51:101–115, 2003.

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•Bum Sik Hong and Tai Young Ahn. (2007) Recent trends in the treatment of testosterone deficiency syndrome. International Journal of Urology 14:11, 981–985
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• Luis Reyes-Vallejo, MD, Stephen Lazarou, MD, and Abraham Morgentaler, MD. (2007) Subjective Sexual Response to Testosterone Replacement Therapy Based on Initial Serum Levels of Total Testosterone. The Journal of Sexual Medicine 4:6, 1757–1762
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• Bu B. Yeap, Osvaldo P. Almeida, Zoë Hyde, S. A. Paul Chubb, Graeme J. Hankey, Konrad Jamrozik and Leon Flicker. Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health In Men Study. Clinical Endocrinology doi: 10.1111/j.1365-2265.2007.03055.x
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• Han M. Hanafy, MD. (2007) Testosterone Therapy and Obstructive Sleep Apnea: Is There a Real Connection?. The Journal of Sexual Medicine 4:5, 1241–1246
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• Kevin R Scott, Anna M Barrett. (2007) Dementia syndromes: evaluation and treatment. Expert Review of Neurotherapeutics 7:4, 407
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• Cheryl A Frye, Kassandra Edinger, Kanako Sumida. (2007) Androgen Administration to Aged Male Mice Increases Anti-Anxiety Behavior and Enhances Cognitive Performance. Neuropsychopharmacology ,
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• Kunihiro Matsushita, Hiroshi Yatsuya, Koji Tamakoshi, Pei Ou Yang, Rei Otsuka, Keiko Wada, Hirotsugu Mitsuhashi, Yo Hotta, Takahisa Kondo, Toyoaki Murohara. (2007) High-Sensitivity C-Reactive Protein is Quite Low in Japanese Men at High Coronary Risk. Circulation Journal 71:6, 820
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• Kenneth J. Ottenbacher, PhD, Margaret E. Ottenbacher, MS, APRN, Allison J. Ottenbacher, BS, Ana Alfaro Acha, MD, and Glenn V. Ostir, PhD. (2006) Androgen Treatment and Muscle Strength in Elderly Men: A Meta-Analysis. Journal of the American Geriatrics Society 54:11, 1666–1673
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• Pieter J. Swart, Walter J. J. Krauwinkel, Ronald A. Smulders and Neila N. Smith. (2006) Pharmacokinetic Effect of Ketoconazole on Solifenacin in Healthy Volunteers. Basic & Clinical Pharmacology & Toxicology 99:1, 33–36

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• D. Finas, M. Bals-Pratsch, J. Sandmann, R. Eichenauer, D. Jocham, K. Diedrich, P. Schmucker & M. Hüppe. (2006) Quality of life in elderly men with androgen deficiency. Andrologia 38:2, 48–53
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• Guy G T??Sjoen, Jean-Marc Kaufman. (2006) Androgen deficiency in aging men. Current Opinion in Endocrinology and Diabetes 13:3, 254???261
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• Laura H. Schopp, Mary Clark, Micah O. Mazurek, Kristofer J. Hagglund, Michael E. Acuff, Ashley K. Sherman, Martin K. Childers. (2006) Testosterone Levels Among Men with Spinal Cord Injury Admitted to Inpatient Rehabilitation. American Journal of Physical Medicine & Rehabilitation 85:8, 678
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• Salvatore Alesci, Massimo U. De Martino, Ioannis Ilias, Philip W. Gold, George P. Chrousos. (2005) Glucocorticoid-Induced Osteoporosis: From Basic Mechanisms to Clinical Aspects. NeuroImmunoModulation 12:1, 1
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• Emily Darby, Bradley D Anawalt. (2005) Male Hypogonadism. Treatments in Endocrinology 4:5, 293
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• J OBRIEN, S LAZAROU, L DEANE, K JARVI, A ZINI. (2005) ERECTILE DYSFUNCTION AND ANDROPAUSE SYMPTOMS IN INFERTILE MEN. The Journal of Urology 174:5, 1932
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• DENNIS H. SULLIVAN, PAULA K. ROBERSON, LARRY E. JOHNSON, OSAMA BISHARA, WILLIAM J. EVANS, EUGENE S. SMITH, J ALLEN PRICE. (2005) Effects of Muscle Strength Training and Testosterone in Frail Elderly Males. Medicine & Science in Sports & Exercise 37:10, 1664
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• T. Diemer, E. W. Hauck, V. Rohde, W. Weidner. (2005) Therapie des „Aging male“. Der Urologe 44:10, 1173
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• Carolyn A. Allan and Robert I. McLachlan. (2004) Age-related changes in testosterone and the role of replacement therapy in older men. Clinical Endocrinology 60:6, 653–670
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• Arvind Modawal, Saba Ansari, Shazia Fazili. (2004) Management of Geriatric endocrine disorders. Comprehensive Therapy 30:1, 10
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• Joel M. Kaufman. (2004) Evolution of delivery systems for testosterone administration. Current Sexual Health Reports 1:3, 109
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• Pär Stattin, Sonja Lumme, Leena Tenkanen, Henrik Alfthan, Egil Jellum, Göran Hallmans, Steinar Thoresen, Timo Hakulinen, Tapio Luostarinen, Matti Lehtinen. (2004) High levels of circulating testosterone are not associated with increased prostate cancer risk: A pooled prospective study. International Journal of Cancer 108:3, 418
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• Michael R Deschenes. (2004) Effects of Aging on Muscle Fibre Type and Size. Sports Medicine 34:12, 809
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• Joshua Blum, R. Hill Harris. (2003) Diagnosis and Treatment of Hypogonadism With Emphasis on Erectile Dysfunction and Osteoporosis. Primary Care Case Reviews 6:3, 97
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• (2003) Anti-Aging Medicine LiteratureWatch. Journal of Anti-Aging Medicine 6:2, 149

The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications

Jean M. Kaufman and Alex Vermeulen
Department of Endocrinology, Ghent University Hospital, Ghent B-9000, Belgium

Correspondence: Address all correspondence and requests for reprints to: Prof. Dr. Jean M Kaufman, Department of Endocrinology 9K12, De Pintelaan 185, Ghent, B-9000, Belgium. E-mail: jean.kaufman@ugent.be

Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum levels below the range for young men. Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established. In fact, minimal androgen requirements for elderly men remain poorly defined and are likely to vary between individuals. Consequently, borderline androgen deficiency cannot be reliably diagnosed in the elderly, and strict differentiation between “substitutive” and “pharmacological” androgen administration is not possible. To date, only a few hundred elderly men have received androgen therapy in the setting of a randomized, controlled study, and many of these men were not androgen deficient. Most consistent effects of treatment have been on body composition, but to date there is no evidence-based documentation of clinical benefits of androgen administration to elderly men with normal or moderately low serum testosterone in terms of diminished morbidity or of improved survival or quality of life. Until the long-term risk-benefit ratio for androgen administration to elderly is established in adequately powered trials of longer duration, androgen administration to elderly men should be reserved for the minority of elderly men who have both clear clinical symptoms of hypogonadism and frankly low serum testosterone levels.

The Effect of Testosterone Replacement on Endogenous Inflammatory Cytokines and Lipid Profiles in Hypogonadal Men

Chris J. Malkin, Peter J. Pugh, Richard D. Jones, Dheeraj Kapoor, Kevin S. Channer and T. Hugh Jones

Department of Cardiology, Royal Hallamshire Hospital (C.J.M., P.J.P., K.S.C.), Sheffield, United Kingdom S10 2JF; Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield (R.D.J., D.K., T.H.J.), Sheffield, United Kingdom S10 2RX; and Center for Diabetes and Endocrinology, Barnsley District General Hospital (D.K., T.H.J.), Barnsley, United Kingdom S75 2EP

Address all correspondence and requests for reprints to: Dr. Chris J. Malkin, Cardiology Department, Royal Hallamshire Hospital, Sheffield, United Kingdom S10 2JF. E-mail: chris.malkin@sth.nhs.uk .

Testosterone has immune-modulating properties, and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNF , IL-1ß, and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10. We report a randomized, single-blind, placebo-controlled, crossover study of testosterone replacement (Sustanon 100) vs. placebo in 27 men (age, 62 ± 9 yr) with symptomatic androgen deficiency (total testosterone, 4.4 ± 1.2 nmol/liter; bioavailable testosterone, 2.4 ± 1.1 nmol/liter). Compared with placebo, testosterone induced reductions in TNF (–3.1 ± 8.3 vs. 1.3 ± 5.2 pg/ml; P = 0.01) and IL-1ß (–0.14 ± 0.32 vs. 0.18 ± 0.55 pg/ml; P = 0.08) and an increase in IL-10 (0.33 ± 1.8 vs. –1.1 ± 3.0 pg/ml; P = 0.01); the reductions of TNF and IL-1ß were positively correlated (rS = 0.588; P = 0.003). In addition, a significant reduction in total cholesterol was recorded with testosterone therapy (–0.25 ± 0.4 vs. –0.004 ± 0.4 mmol/liter; P = 0.04). In conclusion, testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol. Twenty of these men had established coronary disease, and because total cholesterol is a cardiovascular risk factor, and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque, these properties may have particular relevance in men with overt vascular disease.

This work was supported by the Central Sheffield University Hospitals Pilot Research Fund.