The Journal of Steroid Biochemistry and Molecular Biology
Androgen treatment of male hypogonadism in older males☆
Section snippets
Effects of aging on the hypothalamic–pituitary–testicular axis
Baker et al. [12] were the first to clearly show a decline in testosterone with aging. Their study, however, included a number of persons with systemic illness. Four longitudinal studies have shown a decline in testosterone with aging [13], [14], [15], [16]. These studies also demonstrated an increase in SHBG with aging, resulting in an even more marked decline in free or bioavailable testosterone with aging. Total testosterone levels decline at approximately the rate of 1% per annum and
How to measure testosterone
Classically, testosterone levels have been measured by radioimmunoassay. The validity of this method is dependent on the quality of the available antibodies. Over recent years variability in the quality of antibodies has become fairly common. In addition, when new antibodies are introduced, normal ranges with healthy young persons need to be established. Validity of these assays should be confirmed by mass spectroscopy, the true gold standard.
However, a greater problem is whether the true
The androgen receptor, androgen action and aging
A single 99KD androgen receptor binds both testosterone and dihydrotestosterone. The best characterized abnormality of the androgen receptor is Kennedy’s syndrome, a condition associated with spinal and bulbar muscular dystrophy [34]. This condition has an increase in trinucleotide CAG repeats leading to androgen insensitivity. These CAG repeats encode variable length glutamine repeats in the N-terminal of the androgen receptor. The normal CAG repeat lengths range from 6 to 39, with a mean of
Positive effects of testosterone therapy in older persons
Overall, there are limited studies on the effects of testosterone replacement therapy in older persons. Table 3 provides a summary of the findings to date, based on a recent review by us [32]. The majority of studies have found that testosterone increases libido and improves the quality of erections. Morley and Tariq [42] have reported that testosterone will restore erections in persons who originally failed sildenafil. This would appear to be due to the ability of testosterone to enhance the
Frailty, sarcopenia and testosterone
Loss of muscle mass with aging is associated with sarcopenia and frailty [56], [57], [58], [59], [60]. Loss of muscle mass with aging and declining muscle strength is associated with a reduction in free or bioavailable testosterone levels [61], [62], [63]. This decline in testosterone has also been associated with a reduction in function [63]. Testosterone appears to increase lean mass, but the effects on muscle strength are less clearcut [32]. In a small group of frail men receiving
Adverse effects of testosterone
A major side effect of testosterone replacement therapy in older men is the ability of testosterone to stimulate erythropoeisis to produce polycythemia. This occurs in between 6 and 25% of older men [19]. The associated increase in blood viscosity can result in a significant risk of thrombotic events.
In most older men testosterone produces a small increase in prostate specific antigen [19]. No clear relationship between testosterone therapy and the development of benign prostatic hypertrophy or
Symptom screening tests for hypogonadism in older males
Three screening tests for hypogonadism in older males have been developed viz the ADAM [69], the Massachusetts Male Aging Survey (MMAS) Questionnaire [70] and the Aging Male Survey (AMS) [71]. The ADAM has been translated into multiple different languages and is widely utilized throughout the world (Table 4). It was revalidated in French and Belgium [72]. It has excellent sensitivity but in general populations it has a sensitivity around 30%. This can be improved by excluding persons with
Conclusion
Low bioavailable testosterone levels associated with a variety of symptoms are fairly common in middle aged and older men. It is suggested that the appropriate diagnostic approach to the andropause is to utilize one of the symptom screening questionnaires and if it is positive, this should be followed up by the measurement of at least two bioavailable testosterone measurements a week apart. The combination of symptoms and a low bioavailable testosterone level makes the diagnosis of the
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Sex Hormone Binding Globulin: A Review of its Interactions With Testosterone and Age, and its Impact on Mortality in Men With Type 2 Diabetes
2019, Sexual Medicine ReviewsCitation Excerpt :Albumin-bound testosterone may also be bioavailable because binding is weak and interactions with the vascular wall may allow dissociation of steroid during flow through capillaries.42,43 Bioavailable may be a more useful measure of hormone status than total testosterone; for example, its fall during male aging is steeper and associated with features of adult onset TD.44−47 Determination of free or bioavailable testosterone experimentally or using algorithms is relatively demanding because of inter- and intra-laboratory imprecision of available methods and different values for binding parameters.
Sex difference in the relationship between salivary testosterone and inter-temporal choice
2015, Hormones and BehaviorCitation Excerpt :On the basis of these findings, one might think that male participants with high testosterone levels exhibited a reduced preference for immediate rewards because their anxiety was ameliorated by testosterone. Consistent with this interpretation, previous studies have verified the anxiolytic effect of androgens when administered in low therapeutic doses in human males with hypogonadal condition (Morley and Perry, 2003; Wang et al., 1996). However, we think that the anxiolytic effect of testosterone has exerted only limited effect on the participants in the present study for the following reasons.
Comparative determinations of non SHBG-bound serum testosterone, using ammonium sulfate precipitation, Concanavalin A binding or calculation in men
2012, SteroidsCitation Excerpt :Bioavailable testosterone (BT) was reported to be the best in vitro measure of the testosterone availability for tissues and gives a more accurate view of testosterone status [17] than total testosterone (TT). During aging, BT decreases more steeply than TT [18,19], and is associated with various physiological changes, such as a loss of muscle strength [20], decrease of cognitive function [21–24], coronary heart disease, decrease of bone density and hypogonadism [17]. Most of the described BT assays are based upon precipitation of SHBG-bound T by ammonium sulfate, after equilibrating with minute doses of tritiated testosterone [1,7,25] and measuring of TT by radioimmunoassay.
Androgen deficiency in aging and metabolically challenged men
2012, Urologic Clinics of North AmericaCitation Excerpt :Few small studies have examined treatment of men with mild cognitive impairment and/or Alzheimer disease; although 2 show some benefit with T therapy in visuospatial cognition and overall cognitive ability,79,80 another showed no significant difference between cases and controls.81 Once more, disparate findings convey the probable interplay between multiple observed and unobserved factors that contribute to the complex pathophysiology governing AD and cognition, as well as divergent methods in the studies themselves, including differing treatment duration, differing cognitive domains tested, and differing subject characteristics.72,82 For most urologists, the primary contact with hypogonadism is made through men presenting with low libido, ED, or the side effects of androgen deprivation therapy (ADT) as treatment of prostate cancer.
Antiaging Medicine
2010, Brocklehurst's Textbook of Geriatric Medicine and GerontologyThe effect of Tulbaghia violacea extracts on testosterone secretion by testicular cell cultures
2010, Journal of Ethnopharmacology
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Presented at the 11th International Congress on Hormonal Steroids and Hormones and Cancer, ICHS and ICHC, Fukuoka, Japan, 21–25 October 2002.