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Hormonal
Changes in the Aging Male
The
aging of the world's population
During recent decades, the world population's birth and death rates have
undergone a remarkable decline. Consequently, the increasing proportion
of older persons is becoming a major concern. Today, one out of every
ten persons is age 60 or more; by 2050, the proportion is expected to
be one out of five (Figure 1). In the twenty-first century, human beings
are expected to break the 100-year barrier and reach their biological
limit—their longest possible lifespan—of almost 120 years. The socioeconomic
impact on society that may result from an increasing old-age dependency
ratio is an area of growing research and public debate.
Figure
1. Aging of the world's population.
Aging
can refer to the progressive deterioration of cells, tissues and organs
associated with increased age. A distinction must be made between biological
and chronological aging because the primary objective is not only to prolong
life but to allow aging in a state of good health. Starting at middle
age, the death rate doubles every 7 to 10 years as a result of degenerative
geriatric conditions such as cardiac disease, cancer, osteoporosis, arthropathy,
diabetes, dementia and autoimmune disease. One hundred million Americans
are currently being treated for one or more degenerative diseases at a
healthcare cost of more than $700 billion per year. Ninety percent of
all healthcare dollars are spent on extraordinary care in the last two
to three years of life.
The
aging male
Due to genetic predisposition, typical "male" lifestyle, and emotional
and social factors, men in the Western world die on average seven years
earlier than women. Female menopause has been known for centuries, but
only recently has it been discovered that males go through a similar phenomenon,
with analogous symptoms. Names for this phenomenon include male climacteric
and andropause. Menopause represents a landmark in the female chronobiology
and indicates the end of reproductive capacity. In contrast to this clearly
defined event for women, aging of the male endocrine system, beginning
in middle-aged or elderly men, is a less abrupt, less clearly demarcated
and highly variable process (Figure 2). A gradual decrease in nearly all
physiological functions accompanies aging and is reflected clinically
by a decrease in muscle mass and strength, sexual function and activity,
cognitive functions, and the feeling of well-being; and by the development
of abdominal obesity, insulin resistance and atherosclerosis.
Figure
2. General patterns of age-related decline in estradiol levels in
women and total testosterone levels in men.
Hormonal
changes and replacement therapies
The most potent androgen in man is testosterone. It is released by the
testes under the control of LH, which, in turn, is secreted in a pulsatile
manner by the pituitary gland. As men age, the testes may become less
responsive to these LH pulses. Serum total testosterone and calculated
free and non-SHBG-bound testosterone decrease with age; SHBG is reported
to increase. Serum LH and FSH exhibit a mild associated increase. Cortisol
and insulin also increase with age. Both sexes experience similar declines
in DHEA and DHEA-SO4, hGH, IGF-I and melatonin, with a general
reduction in sense of well-being, libido and cognitive abilities. TSH,
another hormone secreted from the pituitary, declines slightly with age,
whereas the concentrations of T3 and T4 do not appear to be affected.
To
follow up these alterations and their clinical and physiological effects,
a knowledge of the hormonal profile is mandatory. Hormone measurements
allow detection of pathological states and provide the necessary information
for proper therapeutic monitoring in such contexts as testosterone replacement
therapy and DHEA intake. Additionally, supplemental hGH, estradiol, melatonin,
vitamin complexes and antioxidants are administered in specific conditions.
Replacing
the hormones that decline with age can help give both women and men longer
and healthier lives. As hormone levels vary widely from one individual
to another, hormone replacement must be carefully balanced and monitored
by measuring the hormonal status of the patient for optimal results.
The
IMMULITE® Aging Male Study
The aim of the study was to verify age-dependent hormonal changes in males
and to establish age-related male reference ranges for these parameters.
Venous blood samples were collected from 300 apparently healthy German
males aged 20 to 86 years, divided into the following age groups of 50
individuals each: 21 - 30, 31 - 40, 41 - 50, 51 - 60, 61 - 70, and > 70
years. Total testosterone, SHBG, DHEA-SO4, estradiol, LH, FSH, TSH, free
T4 and free T3 were measured using the IMMULITE system. The total testosterone
and SHBG results were used to generate free androgen index (FAI) and calculated
free testosterone (cFT) values.1 Medians and central 95% ranges were determined
for all parameters and age groups.
Median
testosterone declined from 18 (21 - 30 y) to 11 nmol/L (> 70 y), the median
FAI from 60 to 22.5, and the median cFT from 0.43 to 0.18 nmol/L; whereas
SHBG increased from 31 to 46 nmol/L. Table 1 shows the percentage of subjects
by age group with testosterone, FAI and cFT values lower than the 2.5th
percentile of the 21 - 30 year age group.
Median
DHEA-SO4 declined from 9.2 (21 - 30 y) to 2.4 µmol/L (> 70 y) and median
estradiol from 107 to 68 pmol/L. Gonadotropin medians increased from 4.2
to 5.0 IU/L for LH, and from 3.7 to 11.2 IU/L for FSH. TSH levels declined
only slightly from 1.4 to 1.0 mIU/L. There was no significant change in
the median free T4 (16.7 to 15.4 pmol/L) or in the median free T3 (4.9
to 4.5 pmol/L). (See Figures 3 and 4.)
Table
1. Percentage of healthy men with testosterone, FAI and cFT values
lower than the 2.5th percentile of the 21-31 year age group.
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