Therapeutic dilemmas for androgen deficiency in aging males (original) (raw)
Related papers
The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications
Endocrine Reviews, 2005
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 agerelated 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. (Endocrine Reviews 26: 833-876, 2005) III. Clinical Significance of the Age-Associated Decrease in Androgen Levels A. Introduction B. Similarities between symptoms of aging and hypogonadism in young men C. Associations between clinical manifestations of aging and sex steroid status D. Summary IV. Diagnosis of Androgen Deficiency in the Aging Male A. Introduction B. Clinical evaluation C. Biochemical evaluation D. Practical approach to diagnosis V. Androgen Treatment in Elderly Men A. Introduction B. Clinical trials with intervention to increase androgen exposure C. Risks of androgen treatment D. DHEA treatment VI. Summary and Conclusions
Androgen deficiency in the aging man
Australian family physician, 2010
Androgen deficiency in the aging man is an area of considerable debate because a gradual decline in testosterone may simply be part of the normal aging process. However, there is an alternative view that androgen deficiency in the aging man may constitute a valid and underdiagnosed disorder. To discuss the aetiology, clinical features, diagnosis and management of androgen deficiency in the aging man. Late onset hypogonadism has clinical features that overlap with both normal aging and some pathological conditions. It can only be diagnosed on the basis of both suggestive clinical features and clear biochemical evidence of testosterone deficiency. In this group of patients medication may play a role.
Best Practice & Research Clinical Endocrinology & Metabolism, 2004
Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-speci®c and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term`andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove bene®cial in some elderly males with low±normal testosterone levels. However, at this point in time, widespread use of testosterone in an elderly male population outside controlled clinical trials seems inappropriate.
Testosterone and Andropause: The Feasibility of Testosterone Replacement Therapy in Elderly Men
Pharmacotherapy, 1999
Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that include weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia, memory impairment, and reduced cognitive function. Free testosterone levels begin to decline at a rate of 1% per year after age 40 years. It is estimated that 20% of men aged 60-80 years have levels below the lower limit of normal. Although the causal relationship between declining testosterone levels and development of andropause symptoms is not firmly established, administration of testosterone to this population resulted in improvements in many areas. Most studies to date focused on physical benefits of testosterone replacement and failed to assess psychologic symptoms rigorously. Preliminary data suggest that therapy may benefit elderly men with new-onset depression. Testosterone administration is not without problems, the most worrisome being the potential for increased prostate cancer risk. Despite this concern, a limited number of studies administered the hormone weekly for up to 2 years, with only mild increases in prostate-specific antigen over control values. Currently, insufficient evidence, primarily regarding psychologic safety and efficacy, exists to warrant general administration of testosterone to elderly hypogonadal men. Further clinical investigations of this therapy in men with low testosterone levels and andropause symptoms are justified and necessary. (Pharmacotherapy 1999;19(8):951-956)
The Journal of Clinical Endocrinology & Metabolism, 2004
Epidemiological studies indicate that normal male aging is associated with a gradual and variable decline in blood testosterone concentrations and unfavorable changes in muscle, bone, and fat that mimic those of androgen deficiency in young men. These age-related reductions in muscle and bone mass and increased fat mass may be responsible for other age-related changes, including decreased muscle strength and physical function, changes in metabolic function, and increased falls, fractures, and disability. Whether age-related relative androgen deficiency truly causes any of these features requires interventional studies specifically in older men, because aged tissues may not remain androgen sensitive nor is such treatment necessarily safe. A Medline search (years 1966 through January 2004, using search terms random and androgen), supplemented by subsequent reference searches of retrieved articles, identified randomized placebocontrolled studies of androgen therapy. These studies show Abbreviations: DHT, Dihydrotestosterone; PSA, prostate-specific antigen; T, testosterone. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community.
Experimental Gerontology, 1993
Androgen levels decrease with aging in men. Androgen deficiency in elderly men may lead to asthenia, decrease in muscle mass, osteoporosis, decrease in sexual activity, and, in some cases, changes in mood and cognitive function. Combination of these factors may result in impaired quality of life in the elderly male. Androgen replacement therapy may increase bone and muscle mass, enhance muscle and cardiovascular function, and improve sexual function and general well-being. These potential benefits of androgens have to be weighed against the possible adverse effects on prostate and cardiovascular diseases. Careful long-term studies will be required to assess the risk-to-reward ratios of androgen or other hormone replacement therapy before the development of treatment strategies similar to estrogen and progestagen substitution therapy for the postmenopausal female.
Relative Testosterone Deficiency in Older Men: Clinical Definition and Presentation
Endocrinology and Metabolism Clinics of North America, 2005
The increased longevity observed in many communities worldwide has created a need to foster healthy aging. Devising safe and effective medical approaches that prolong healthy, independent, and enjoyable living is therefore a priority for health care providers. Androgen replacement therapy for older men holds promise in this regard, because systemic levels of testosterone fall by 1% to 2% each year, creating a state of relative (compared with young men) androgen deficiency [1,2]. Furthermore, many aspects of aging resemble features of organic androgen deficiency in younger men in whom testosterone replacement is an accepted therapy and widely regarded as safe, affordable, and effective [3,4] (Table 1). In contrast, androgen replacement therapy in older men remains controversial for numerous reasons [5,6]. First, rigorous data confirming agespecific benefits over potential long-term adverse effects are limited. Second,
Testosterone for the aging male; current evidence and recommended practice
Clinical Interventions in Aging, 2008
An international consensus document was recently published and provides guidance on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men. The diagnosis of LOH requires biochemical and clinical components. Controversy in defi ning the clinical syndrome continues due to the high prevalence of hypogonadal symptoms in the aging male population and the non-specifi c nature of these symptoms. Further controversy surrounds setting a lower limit of normal testosterone, the limitations of the commonly available total testosterone result in assessing some patients and the unavailability of reliable measures of bioavailable or free testosterone for general clinical use. As with any clinical intervention testosterone treatment should be judged on a balance of risk versus benefi t. The traditional benefi ts of testosterone on sexual function, mood, strength and quality of life remain the primary goals of treatment but possible benefi cial effects on other parameters such as bone density, obesity, insulin resistance and angina are emerging and will be reviewed. Potential concerns regarding the effects of testosterone on prostate disease, aggression and polycythaemia will also be addressed. The options available for treatment have increased in recent years with the availability of a number of testosterone preparations which can reliably produce physiological serum concentrations.