ANTIAGEING_AF2 - page 12

Monographic special issue:
Agro FOOD Industry Hi Tech
- vol. 28(2) - March/April 2017
KEYWORDS: Testosterone, Testosterone Replacement Therapy (TRT), Late Onset Hypogonadism (LOH), testofen, re-partitioning, healthy ageing.
Age-related changes in levels of testosterone and the symptoms associated with these changes have
created growing interest in testosterone replacement therapy (TRT). The epidemiology of the andropause
is reviewed, together with the rationale, uses and limitations of classical TRT, and new developments in testosterone re-partitioning
utilising a natural (food-derived) product.
Testosterone and healthy ageing
Total testosterone concentrations decrease in men as part of the
normal ageing process at a rate of 1% -2% per year after the age
of 40 (1-4). This decrease varies considerably between individuals,
and while the cause of declining testosterone is unclear, it is likely
due to a combination of reduced hypothalamic gonadotropin
releasing hormone outflow, alterations in androgenic negative
feedback and decreased responsiveness of testicular tissue (5).
This decline in testosterone is associated with decreased albumin
and increased sex hormone-binding globulin (SHBG), resulting in
higher levels of serum testosterone binding to SHBG and causing
an additional decrease in free (bioavailable) testosterone (6). The
adverse effects of low free testosterone are diverse, potentially
serious and – once recognised – relatively easily addressed.
While testosterone is a pluripotent hormone with a wide range
of biological functions, the clinical significance of a low or low-
normal testosterone level in men is incompletely understood (7).
Notwithstanding, declining testosterone is frequently associated
with loss of stamina and lean musclemass, increased abdominal
fat, reduced libido, anxiety, irritability, fatigue, depression and loss of
drive and focus – a constellation of symptoms sometimes referred
to as the andropause – which impact negatively on quality of life
and relationships (7, 8). As testosterone levels fall further, there is
loss of bone density progressing to osteoporosis and further loss of
muscle progressing to sarcopenia, which confers an increased
risk of obesity, diabetes, osteoporosis, frailty syndrome, cognitive
decline / dementia, cardio-vascular disease and death (9, 10).
For these reasons, low testosterone is associated with increased
morbidity and mortality from all causes (ie 11-15).
The wide range of symptoms reported in middle-aged and
older males has created a significant market for testosterone-
replacement therapy (TRT). It is unfortunate that much of this has
focused on, and been driven by, testosterone’s anabolic and pro-
libidinous effects; because while these are undoubtedly relevant
to some males, the overall effects of TRT on male health are wider
and more valuable. A 2007 review summarized: ‘
Based on current
knowledge, testosterone replacement therapy is unlikely to pose
major health risks in patients without prostate cancer and may
offer substantial health benefits.’
The use of TRT is rapidly becoming a public health issue, due to
the large and increasing numbers of ageing males presenting
with the symptoms of andropause or more accurately late-
onset hypogonadism (LOH). The proportion of men fulfilling a
biochemically-defined diagnosis of LOH increases with aging.
Twenty percent of men aged over 60 have total testosterone
levels below the normal range and the figure rises to 50% in
those aged over 80. The numbers of men presenting with low
free testosterone are even higher, as would be expected in view
of the concurrent increase in SHBG levels (17). This was formally
recognized in 2005:
‘A clinical and biochemical syndrome
associated with advancing age and characterised by typical
symptoms and a deficiency in serum testosterone levels. It [late-
onset hypogonadism] may result in significant detriment in the
quality of life and adversely affect the function of multiple organ
This provides the baseline for current ISA, ISSAM, and
EAU recommendations, and is reflected in the fact that medical
prescribing of TRT has increased by over 300% in the last decade
(19), with continuing strong growth predicted (20).
There are disagreements about who should qualify for TRT, largely
because the numbers of patients presenting with the symptoms
of andropause are undoubtedly greater than those who qualify
as LOH on strict biochemical grounds. This discrepancy has
several probable causes, one of which is the emerging concept
of testosterone-resistance (functionally similar but mechanistically
different from insulin resistance), whereby low / borderline normal
levels of testosterone are rendered hypo-functional due to
postulated second messenger inadequacy (21, 22).
TRT is not a panacea for the ageing male, and there are safety
issues that must be taken into account when considering this
Fellow, Institute of Food, Brain and Behavior,
Oxford, United Kingdom
Paul R. Clayton
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