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

Kaufman, Jean; Vermeulen, A.

doi:10.1210/er.2004-0013

Cited by 950 publications

(840 citation statements)

References 467 publications

(342 reference statements)

Supporting

Mentioning

787

Contrasting

Unclassified

Order By: Relevance

“…Testosterone plays an indispensable role in the development of the male reproductive system during fetal life, triggers the development of secondary sexual characteristics at puberty, and maintains sexual function and bone and muscle health during adulthood 1. Low concentrations of testosterone can occur for a variety of reasons.…”

mentioning

confidence: 99%

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

Basit

Amory

Prasad

2018

Clinical Translational Sci

View full text Add to dashboard Cite

Development of an oral testosterone therapy has proven extremely challenging because of extensive and variable first‐pass metabolism. We investigated the in vivo metabolism of testosterone with increasing oral doses of testosterone, both alone and with the co‐administration of dutasteride (5α‐reductase inhibitor) by liquid‐chromatography tandem mass spectrometry (LC‐MS/MS). In eugonadal men prior to dosing, the circulating concentration of testosterone, androstenedione, etiocholanolone‐glucuronide, and androsterone‐glucuronide was 8.6, 20.9, 9.1, and 55.3%, respectively, of the total testosterone‐related species, whereas testosterone‐glucuronide was ∼1%. When testosterone was dosed orally to men with experimental hypogonadism, a proportion of testosterone‐glucuronide increased to 13%. Dutasteride treatment significantly decreased levels of androsterone and its metabolites. This work reveals extensive metabolism of orally dosed testosterone to androsterone glucuronide via androstenedione, with testosterone‐glucuronide appearing to be the second most important metabolite. This information is of importance in the development of an effective oral testosterone therapy and may have implications for testosterone doping research.

show abstract

mentioning

confidence: 99%

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

Basit

Amory

Prasad

2018

Clinical Translational Sci

View full text Add to dashboard Cite

show abstract

“…In humans, from the age of 50 years onwards, the plasma levels of T decrease progressively with age, whereas ageing has the opposite effect on the plasma concentration of steroid hormone binding globulin whose concentration increases 22, 28. Both changes severely curtail the levels of free plasma T and hence its bioavailability.…”

Section: Discussionmentioning

confidence: 99%

“…This finding has fuelled many trials in the use of TRT as a possible treatment for sarcopenia. However, in E men, TRT reverses some but not all the effects of sarcopenia 17, 22. It is also associated with several side effects including an increase in the risk of developing prostate cancer and gynecomastia, alterations in the composition of plasma lipids, and increased cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres

Wendowski

Redshaw

Mutungi

2016

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

BackgroundSarcopenia, the progressive decline in skeletal muscle mass and function with age, is a debilitating condition. It leads to inactivity, falls, and loss of independence. Despite this, its cause(s) and the underlying mechanism(s) are still poorly understood.MethodsIn this study, small skeletal muscle fibre bundles isolated from the extensor digitorum longus (a fast‐twitch muscle) and the soleus (a slow‐twitch muscle) of adult mice of different ages (range 100–900 days old) were used to investigate the effects of ageing and dihydrotestosterone (DHT) treatment on protein synthesis as well as the expression and function of two amino acid transporters; the sodium‐coupled neutral amino acid transporter (SNAT) 2, and the sodium‐independent L‐type amino‐acid transporter (LAT) 2.ResultsAt all ages investigated, protein synthesis was always higher in the slow‐twitch than in the fast‐twitch muscle fibres and decreased with age in both fibre types. However, the decline was greater in the fast‐twitch than in the slow‐twitch fibres and was accompanied by a reduction in the expression of SNAT2 and LAT2 at the protein level. Again, the decrease in the expression of the amino acid transporters was greater in the fast‐twitch than in the slow‐twitch fibres. In contrast, ageing had no effect on SNAT2 and LAT2 expressions at the mRNA level. Treating the muscle fibre bundles with physiological concentrations (~2 nM) of DHT for 1 h completely reversed the effects of ageing on protein synthesis and the expression of SNAT2 and LAT2 protein in both fibre types.ConclusionFrom the observations that ageing is accompanied by a reduction in protein synthesis and transporter expression and that these effects are reversed by DHT treatment, we conclude that sarcopenia arises from an age‐dependent reduction in protein synthesis caused, in part, by the lack of or by the low bioavailability of the male sex steroid, DHT.

show abstract

“…In younger men improvement of the symptoms of hypogonadism upon testosterone replacement has been convincingly proven. Presently, the statistical decline of serum testosterone in aging men is solidly documented [1,3]. So, it is tempting to associate the above described features of aging to the concurrent decline of androgen action in the elderly, and to assume that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of signs and symptoms of aging.…”

Section: Late Onset Hypogonadism (Loh) Vs Classical Hypogonadismmentioning

confidence: 99%

“…When Prof. Alex Vermeulen from Gent/Belgium in the 1970s started his pioneering work on the decline of testosterone levels in aging men, his work seemed to most professionals only of theoretical interest (for review: [1]). But further studies have substantiated that, with age, a significant percentage of men over the age of 60 years have serum testosterone levels below the lower limits of normal for young adult men (aged 20-30 years) [2,3].…”

Section: Introductionmentioning

confidence: 99%

Androgens and male aging: current evidence of safety and efficacy

Gooren¹

2010

Asian J Androl

View full text Add to dashboard Cite

Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment.

show abstract

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

Cited by 950 publications

References 467 publications

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres

Androgens and male aging: current evidence of safety and efficacy

Contact Info

Product

Resources

About