Category Archives: Androgen

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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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.

Journal of Alzheimer’s Disease

Issue: Volume 5, Number 4 / 2003
Pages: 267 – 269

Relationship between testosterone, sex hormone binding globulin and plasma amyloid beta peptide 40 in older men with subjective memory loss or dementia
M.J. Gillett A1, R.N. Martins A2, R.M. Clarnette A3, S.A.P. Chubb A4, D.G. Bruce , B.B. Yeap
A1 Department of Endocrinology and Diabetes, Fremantle Hospital, Western Australia, Australia
A2 Sir James McCusker Alzheimer’s Disease Research Unit, Hollywood Private Hospital and School of Psychiatry and Clinical Neurosciences, University of Western Australia, Australia
A3 Department of Community and Geriatric Medicine, Fremantle Hospital, Australia
A4 Biochemistry Department, Fremantle Hospital, Australia
A5 School of Medicine and Pharmacology, University of Western Australia, Australia
Abstract:
In a group of 28 older men with either subjective memory loss or dementia, serum total testosterone and sex hormone binding globulin (SHBG) correlated inversely with plasma levels of amyloid beta peptide 40 (Ag40, r=-0.5, P=0.01 and r=-0.4, P=0.04, respectively). Calculated free testosterone was also inversely correlated (r=-0.4, P=0.03), and all three relationships remained statistically significant after allowing for age. A similar but non-significant trend was seen with dehydroepiandrosterone sulphate (DHEAS), and neither luteinising hormone (LH) nor estradiol correlated with Ag40. These data demonstrate that lower androgen levels are associated with increased plasma Ag40 in older men with memory loss or dementia, suggesting that subclinical androgen deficiency enhances the expression of Alzheimer’s disease-related peptides in vivo. An inverse correlation exists between SHBG and Ag40, warranting further investigation.

Testosterone and Depression in Aging Men

Testosterone and Depression in Aging Men
Stuart N. Seidman, M.D., and B. Timothy Walsh, M.D.
Received September 29, 1997; accepted February 24, 1998. From the Department of Psychiatry, College of Physicians and Surgeons of Columbia University; and the New York State Psychiatric Institute. Address correspondence to Dr. Seidman, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 722 West 168th St. Unit 98, New York, NY 10032.
In men, testosterone secretion affects neurobehavioral functions such as sexual arousal, aggression, emotional tone, and cognition. Beginning at approximately age 50, men secrete progressively lower amounts of testosterone; about 20% of men over age 60 have lower-than-normal levels. The psychiatric sequelae are poorly understood, yet there is evidence of an association with depressive symptoms. The authors reviewed 1) the physiology of the hypothalamic-pituitary-gonadal axis and its changes with age in men; and 2) the evidence linking testosterone level and major depression in men. Data on this relationship are derived from two types of studies: observational studies comparing testosterone levels and secretory patterns in depressed and nondepressed men, and treatment studies using exogenous androgens for male depression. The data suggest that some depressed older men may have state-dependent low testosterone levels and that some depressed men may improve with androgen treatment.