Age-related changes in testosterone and the role of replacement therapy in older men (original) (raw)
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EMAS position statement: Testosterone replacement therapy in the aging male
Maturitas, 2015
Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. Literature review and consensus of expert opinion. Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function a...
2000
We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40 -70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up. Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, sim-ilarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally.
Testosterone supplementation in older men: a rational idea whose time has not yet come
Journal of andrology
Forty years after the introduction of estrogens, the debate over the risks and benefits of estrogen replacement therapy in postmenopausal women is still not entirely settled. In contrast, the issues of testosterone replacement in older men are just beginning to be addressed. There is agreement that total, free, and bioavailable testosterone (ie, not bound by sex hormone-binding globulin) levels decline progressively with advancing age (
Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men
The Journal of Clinical Endocrinology and Metabolism, 2001
Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is the result of the aging process per se, as opposed to chronic illness, medication use, and other age-related factors, remains controversial. The frequency with which aging leads to T levels consistent with hypogonadism has also not been defined. These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat. We measured T and sex hormone-binding globulin (SHBG), by RIA, in stored samples from 890 men in the Baltimore Longitudinal Study on Aging. Using a mixed-effects model, we found independent effects of age and date of sampling to reduce T levels. After compensating for date effects, which investigation suggested was artifactual, we observed significant, independent, ageinvariant, longitudinal effects of age on both T and free T index (free T index ϭ T/SHBG), with an average change of Ϫ0.124 nmol/L⅐yr and Ϫ0.0049 nmol T/nmol SHBG⅐yr. T, but not free T index, also decreased with increasing body mass index. Use of Ϫblocking drugs was associated with higher T and higher free T index levels. Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed. Our observations of health factor independent, age-related longitudinal decreases in T and free T, resulting in a high frequency of hypogonadal values, suggest that further investigation of T replacement in aged men, perhaps targeted to those with the lowest serum T concentrations, are justified.
Testosterone and Dehydroepiandrosterone Treatment in Ageing Men: Are We All Set?
The World Journal of Men's Health, 2019
of the World Federation of the Societies of Biological Psychiatry (WFSBP) Although demographic statistics show that populations around the world are rapidly ageing, this rising life expectancy is accompanied by an increase in the number of people living with age-related chronic conditions, such as frailty, cognitive decline, depression, or sexual dysfunction. In men, a progressive decline in androgens occurs with increasing age, and low androgen levels are associated with age-related chronic conditions. However, androgen administration studies are inconclusive, showing differing results according to the androgen used (testosterone [T], dehydroepiandrosterone [DHEA]), the group of men examined (younger vs. older; eugonadal vs. hypogonadal) and the conditions studied (frailty, cognitive decline, depression, sexual dysfunction). In this review, the current state for the use of T and DHEA therapy in men for the age-related conditions is examined. Due to the progressive age-related decline in androgens leading to a higher rate of older men having low androgen levels, the effects of androgen treatment in elderly males will be of particular interest in this review. Doseresponse relationships, the role of potential moderators, and the androgen treatment-related risk for adverse events will be discussed. Studies have suggested that T treatment-more so than DHEA treatment-may be an effective therapy against agerelated chronic conditions in men with low T levels; especially older men. Such conditions include frailty, depression, or sexual dysfunction. However, T treatment does not emerge as an effective therapy against cognitive decline. Nevertheless, more high-quality, randomised controlled trials using T treatment for age-related chronic conditions are necessary if further conclusions are to be made.
Current Opinion in Endocrine and Metabolic Research, 2019
The T Trials were a coordinated set of seven double-blind, placebo-controlled trials to assess efficacy and safety of testosterone versus placebo gel treatment for one year in 788 older men 65 years or older with hypogonadism who had self-reported and objective impairment of sexual and physical function and/or vitality and an average of two morning serum testosterone concentrations < 275 ng/dL. Testosterone dose was adjusted to the mid-normal range for young men. Compared to placebo, testosterone treatment moderately improved sexual function, hemoglobin concentration and corrected anemia, and slightly improved walking distance, vitality, mood and depressive symptoms and bone density and strength, but did not improve cognitive function. Testosterone treatment slightly increased non-calcified and total plaque volume; while concerning, the clinical significance of this finding is not clear. Testosterone treatment also increased PSA levels and referral for urological evaluation, and caused erythrocytosis in some men. The T Trials provided definitive evidence for short-term clinically meaningful, albeit modest benefits and risks of testosterone treatment in older men with unequivocal age-related hypogonadism. Larger and longer-term placebo-controlled clinical trials are needed to assess the long-term benefits and risks of testosterone treatment on clinical outcomes such as frailty, depression, fractures, prostate cancer and cardiovascular events.
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.