There is disagreement among
professionals in the medical community regarding the clinical
significance of the age related decline of Male Testosterone Levels.
As a result of this uncertainty with regard to the nature of Low
Testosterone and the aging man, guidelines have been updated
suggesting the Adult-Onset Hypogonadism be regarded as a quantifiable
medical condition that occurs as a result of changes in biochemistry
that occur during the aging process.
Adult-Onset Hypogonadism is now
characterized with a slate of specific symptoms, and the diagnosis of
this syndrome is the result of a diagnosis of clinically low
Testosterone Levels combined with the experience of those symptoms.
The problem is that since Adult-Onset Hypogonadism has only recently
been fully quantified as a medical disorder, there is a lack of
clinical data which considers Testosterone Deficiency in lieu of all
of the symptoms that have now been scientifically linked to Low T.
Data is especially slim among patients who suffer from this form of
natural Testosterone Deficiency rather than a pathological form of
Testosterone decline which is not directly correlated with age.
Testosterone Deficiency Linked to
Many Disorders
Even though there is a well known
list of symptoms that are associated with a severe deficiency of
Testosterone in younger males, the symptoms which are displayed in
older men are not specific only to Low Testosterone and there are
many other relatively common disorders which can produce many similar
symptoms.
Low Testosterone in younger patients
in considered less than 6 to 8 nanomolars per liter. Because of the
large gray area that exists in which Adult-Onset Hypogonadism shares
many symptoms with other disorders, the exact Testosterone levels
which are associated with Testosterone Deficiency and the precise
negative health risks that are associated with the disorder are no
well delineated. At this point, the threshold for Low-Testosterone is
relatively arbitrary, and there is a movement to discover this
threshold with greater accuracy.
The participants of this study come
entirely from two age groups. The first group of patients is
middle-aged, and the second group is elderly. The goal of the study
was to characterize the medical symptoms related with Testosterone
Deficiency and to distinguish the various thresholds which can be
associated with different levels of symptomatic severity. The
ultimate goal of the study was to demarcate a more exact set of
criteria for the diagnosis of Adult-Onset Hypogonadism based upon the
experience of symptoms and their severity and various rates of
Testosterone Deficiency.
Testosterone Research Methods
Participant Pool
In this study, the researchers
selected a random assortment of men to investigate, organized by age.
These men were participants in a study known as the European Male
Aging Study (EMAS). This clinical study involved eight different
medical centers across Europe. Individual cases were selected from
clinics in Spain, Italy, Hungary, Poland, Estonia, Sweden, Belgium,
and the United Kingdom. The participants in this investigation ranged
in age from forty to seventy-nine years of age. Each participant
selected for the EMAS study was tested in a number of different ways.
Each patient completed a
questionnaire in which they self-reported their current health
condition. In addition to this, each participant completed mental and
physical aptitude tests. Each patient also provided a blood sample
which was diagnostically evaluated in order to ascertain hormone and
biochemical measurements.
8416 participants were encouraged to
join the study, and 3369 of these men were chosen. The mean age of
the subjects was 59.7 years of age. There were no particular
exclusionary criteria by which potential participants were
disregarded. The response rate at each medical center averaged 43%,
with the lowest response rate 24% and the highest response rate 60%.
Although we will not go into detail regarding the specifics of the
original study, the study was sufficiently peer reviewed and the
methods, recruitment criteria, and study design were considered
completely scientifically sound.
Testosterone Medical
Questionnaires
The questionnaires used in this study
posed a variety of questions regarding the general and specific
health of each individual patients. Participants were asked questions
regarding their perception of their overall health. They were asked
what medications they currently used. Additionally, subjects were
asked about particular details regarding their lifestyle and also
provided information concerning their demographic and socioeconomic
status. Certain questionnaires were answered with the assistance of a
interviewer. The three most notable were the Beck Depression
Inventory, a 36 question health survey, and a questionnaire developed
specifically for EMAS regarding sexual ability and function.
Laboratory and Clinical
Assessments
After patients filled out the various
medical questionnaires, they were physically analyzed. The weight and
height of each patient was recorded. In addition to this, the
Body-Mass Index of each patient was calculated based upon biometric
data as well. Waist size was also recorded. Each subject also
consented to an intravenous blood sample drawn from the vein after a
single period of fasting. This blood sample was drawn relatively
early in the day, before In addition to these measurements, each
participant also had his Total Testosterone Levels analyzed via a
method known as gas chromatography-mass spectrometry, abbreviated
GC-MS.
GC-MS is a method of separating
individual molecules in a sample from one another, make it possible
to measure exceedingly small amounts of substances from a small
sample. The participant with the lowest Testosterone Level produced a
measurement of 0.17 nanograms per liter. GC-MS measurements were
accurate to within 2.9%-3.4%. Globulin levels were also assessed via
an immunoassay. Globulins are a type of blood protein that has the
ability to bind with sexual hormones such as Testosterone. Levels of
Free Testosterone were deduced from the measurements of albumin,
globulin, and Total Testosterone, providing a precise yet indirect
measurement.
Validation and Training Sets
The complete group of participants
was randomly separated into two subdivisions. One group was analyzed
as a training set, and the other group represented a validation set.
In order to accomplish the ultimate goal of the study, to delineate
the biochemical and clinical criteria for Adult-Onset Hypogonadism,
researchers monitored a variety of potential symptoms recorded the
rate at which they occurred and the severity of the symptoms in
relation to various Endogenous Testosterone Levels. The links between
Testosterone Deficiency and particular symptoms that were perceived
within the training set were later evaluated independently among
those in the validation set.
As the researchers reviewed the
training set, they selected thirty two items from the EMAS
questionnaires in order to evaluate the perceived symptoms in regard
to their correlation with Testosterone Levels. These thirty two items
were chosen based on the results and outcomes of a number of previous
studies and also particular scientific recommendations. Each of the
items was investigated in order to deduce which of the symptoms were
highly correlated with a Deficiency of either Free or Total
Testosterone Levels. The correlations were statistically analyzed
with the use of regression modeling.
Only items that displayed a high
level of correlation with rates of Free and Total Testosterone were
chosen. In the end, the patients were further divided into two more
groups: Those who experienced a particular symptom, and those who did
not experience a particular symptom. Another form of statistical
analysis known as the Mann-Whitney test was utilized in order to
prove statistical significance between the two participant groups.
Testosterone Study Statistical
Analysis
When analyzing the participants
grouped within the training set, the researchers made use of a
weighted linear regression in order to accurately identify the
Testosterone Level at which the odds of developing a particular
symptom became significant in comparison to the average prevalence of
all subject of the study. Each analysis was weighted in regard to the
age of the participant and the individual center in which a
particular portion of the study was conducted.
Weighting the results of each
individual center is necessary in order to account for any potential
variation that may be the result of imperfections associated with a
particular clinical environment. All of these statistical models were
selected and utilized in order to produce more accurate results and
more precisely pinpoint the threshold at which particular
Testosterone levels were associated with increased risk of developing
a particular Low-T Symptom.
After gathering, controlling, and
smoothing data, the researchers set out to create a visual
representation based upon the correlation of Testosterone Level and
Symptom Presence. These charts were designed in order to show which
symptoms seem to appear in correlation with particular levels of
Testosterone Deficiency. After the charts were outlaid, further
statistical analysis was performed in order to determine with high
accuracy whether each graphical grouping of symptoms truly
represented a cluster of related data points and not a semi-random
array of such points.
In order to more accurately quantify
the relationship between symptom prevalence and Testosterone level,
the researchers made use of further regression models in order to
provide a statistical measurement of the correlation between the
experience of multiple symptoms and particular Low-T levels. After
these statistical measurements were quantified in the Training set,
they were measured for validity by comparing the results found in the
training set to the data within the validation set. If the
symptomatic correlations matched between the two groups, then the
thresholds are independently validated by a different and unique set
of data.
After discovering which symptomatic
correlations were independently verifiable, this data was used in
order to delineate specific minimum criteria for the diagnosis of
Adult-Onset Hypogonadism. Further statistical techniques were used in
order to further validate the accuracy of the obtained results. After
all of this statistical modeling, the last issue in order to provide
the most diagnostically useful results was to statistically control
the data for confounding effects such as BMI, age, and comorbid
illness which could increase the prevalence of certain symptoms or
cause them to occur independently of Low-Testosterone levels.
Testosterone Study Results
Out of the 3360 individuals who
participated in the study, 150 were rejected from this analysis as a
result of primary hypogonadism, known pituitary disorders, or the
usage of medicines which had the ability to alter testicular or
pituitary function or increase the rate at which androgens are
cleared from the body. After the exclusion of these 150 subjects
there were 3219 males whose data was utilized in this
scientific study.
Correlation between Testosterone
Levels and Particular Symptoms
From the initial selection of thirty
two potential symptoms of Low-Testosterone which were analyzed in the
training set, nine of those symptoms were proven to be correlated
with Levels of Free of Total Testosterone Level. These nine symptoms
displayed a significantly unique difference between asymptomatic
participants and symptomatic participants.
Three of these symptoms were directly
related to sexual function. Individuals with abnormally low
testosterone were found to have a higher incidence of erectile
dysfunction, decreased libido, and lower than average frequency of
early morning erection. Three of the statistically significant
symptoms were physical in nature. Participants with comparatively Low
Levels of Testosterone were more likely to be unable to stoop, kneel
or bend. In addition to this, these patients also considered
themselves unable to walk a distance greater than a single kilometer.
The last physical symptom was that
subjects with Low-T were more likely to be unable to engage in
strenuous physical activity without experiencing fast and
overwhelming fatigue. The final three symptoms which were considered
clinically significant were psychological in nature. Patients with
comparably Low Testosterone were more likely to experience fatigue
easily in their daily life. In addition to this, they lacked energy
and motivation. Third, these patients were more likely to experience
symptoms of depression and sadness.
Minimum Testosterone Deficiency
Thresholds
As the researchers hypothesized, the
severity of these nine symptoms all become greater as Testosterone
Levels declined. Below are the exact data points for each symptom.
The minimum threshold for:
Reduced libido - 8 nanomolars
per liter Total Testosterone
Erectile Dysfunction - 8.5
nanomolars per liter Total Testosterone
Reduced Frequency of Early
Morning Erection - 11 nanomolars per liter Total Testosterone
Hindered Overall Well-Being -
13 nanomolars per liter Total Testosterone
The Threshold for Free Testosterone
Deficiency for the three sexually related symptoms of Low-T were 160,
280, and 280 picomoles per liter. The threshold for both fatigue and
sadness was 160 picomoles per liter.
There were no thresholds discovered
regarding the association of Free Testosterone and Physical symptoms,
nor Total Testosterone and Psychological Symptoms. Although
symptomatic probability was around 25%, testosterone levels were
located in what would undoubtedly be considered the normal range for
endogenous Testosterone production. Only seven subjects analyzed
displayed Testosterone Levels greater than thirty five nanomolars per
liter. This may have caused there to be an ultimately statistically
insignificant correlation between erectile dysfunction and high
levels of Total Testosterone.
Lower Testosterone Strongly Linked
to Higher Prevalence of Symptoms
Statistical regression analysis shows
that Lower Levels of Testosterone are strongly correlated with the
increased prevalence of physical and sexual symptoms. The further
below the normal threshold, the more likely the patient was to become
symptomatic. In the case of reduced frequency of early morning
erection, having Total Testosterone levels a single nanomolar below
threshold (11) increased the odds of suffering from this symptom by a
ratio of 1.1 to 1. Having Total Testosterone Levels above 11
nanomolars per liter was not correlated with increased or decreased
prevalence of the symptom. This means that if an individual has an
above-threshold Total Testosterone rate for this symptom that the
incidence plateaus. All individuals with greater than 11 nanomolars
of Free Testosterone per liter have a statistically similar chance of
experiencing decreased frequency of morning erections.
For the other two sexual symptoms,
reduced libido and erectile dysfunction, different values were
obtained regarding distance from threshold. Total Testosterone levels
one nanomolar per liter below threshold resulted in an increased risk
of the symptom by a ratio of 1.48 to 1. In regard to erectile
dysfunction, the same drop from threshold was correlated by a ratio
of 1.23 to 1. The threshold for decreased capacity for strenuous
activity was pinpointed at 13 nanomolars per liter. A similar
reduction of a single nanomolar in the group increased the the
prevalence ratio by 1.11 to 1.
The threshold for reduced libido and
increased depression in regard to Free Testosterone was 160 picomoles
per liter. For reduced frequency of morning erection and erectile
dysfunction, the value was 280 picomoles per liter Free Testosterone.
Finally, the Threshold for amplified fatigue was also 160 picomoles
per liter Free Testosterone.
Symptom Clustering and Low
Testosterone
Employing the data in the training
set, statistical analysis allowed the researchers to correlated
significant symptoms with one another. The analysis also allowed the
researchers to correlate these symptoms with both Normal and Low
Testosterone. Through this strategy of analysis, the researchers were
able to find two significant symptom clusters. The majority of
completely asymptomatic participants had Total Testosterone Rates
greater than 8 nanomolars per liter and a Free Testosterone rate of
at least 220 picomoles per liter.
The majority of patients that
suffered from sexual symptoms of Low-T have Total Testosterone Rates
below 8 nanmolars per liter, and a Free Testosterone Rate lower than
220 picomoles per liter. For the purposes of this particular study,
physiological symptoms that were not clustered together were not
considered to be the result of Low-T but the result of some other
underlying health malfunction. When these same hypotheses were
compared to the validation set, similar results occurred, proving
that the clustering effect was not a fluke.
Hypogonadism Criteria
The analysis of the data shows that
the greater the deficiency in Testosterone, the higher the prevalence
of the particular sexual symptom. This relationship was inverse and
incredibly consistent. Low Testosterone was considered clinically
diagnosable in this study if all three sexual side effects of Low-T
were present and Total Testosterone Levels were below 11 nanomolars
per liter. Free Testosterone levels below 220 picomoles per liter
further increased the risk of sexual side effects of Testosterone
Deficiency.
Based on the data provided in this
study is is safe to conclude that patients with Free Testosterone
Levels under 220 picomoles per liter and Total Testosterone Levels
under 11 nanomolars per liter have clinically low levels of
Testosterone. In order for Low-T to be properly medically diagnosed,
however, Testosterone levels should both be beneath these thresholds
while the patient also displays multiple symptoms of Testosterone
Deficiency.
Approximate Prevalence of
Hypogonadism
Within the group of patients analyzed
in this study, 4.1% of participants experienced a Total Testosterone
Rate beneath 8.0 nanomolars per liter. 17% of subjects had Total
Testosterone Rates beneath 11 nanomolars per liter. If Adult-Onset
Hypogonadism is defined as the experience of three symptoms of sexual
dysfunction combined with a Free Testosterone Level lower than 220
picomoles per liter, Total Testosterone Rate beneath 11 nanomolars
per liter, this would mean that 2.1% of individuals suffer from
Adult-Onset Hypogonadism.
Based on these criteria, the rate
increases at a steady pace. 0.1% of patients in their forties, 0.6%
of patients in their fifties, 3.2% of patients in their sixties, and
5.1% of patients in their seventies experience significant
Testosterone Deficiency. These percentages are controlled to
represent and otherwise healthy population, however. Increased body
fat and BMI can increase the percentages significantly, and many
comorbid illnesses also enhance the risk of Testosterone Deficiency.
Testosterone Study Discussion
As a result of this large and
systematic analysis of male patients with regard to potential
underlying Testosterone Deficiency, the researchers were able to
produce a tentative set of guidelines with which to undoubtably
diagnose a certain subset of patients with Adult-Onset Hypogonadism.
In this analysis it was observed that a number of symptoms associated
with non-age related hypogonadism were not correlated with the
Decline in Testosterone Rates in older males. When analyzing the data
based on the 9 statistically significant symptoms, differences in
Average Testosterone Rates among asymptomatic and symptomatic
patients was only modest. The researchers conclude that this reflects
a weak total correlation between Testosterone Levels and Testosterone
Symptoms among this group.
Continued analysis showed that there
existed definite hard thresholds in regard to Testosterone levels and
various forms of sexual dysfunction. These negative symptoms occurred
near or beneath the lower threshold for adult hypogonadism in young
males.
Sexual Dysfunction Most Important
Measure of Testosterone Deficiency
For this reason, the sexual symptoms
of Testosterone Deficiency are incredibly important for the proper
diagnosis of elderly males, but suggest that Testosterone Deficiency
should only be diagnosed in Testosterone Levels are obviously below
normal. Low Testosterone was tightly correlated with reduced overall
physical energy and endurance. This corroborates with other studies
regarding Testosterone Levels and the elderly. Psychological
Testosterone Deficiency Symptoms produced no clustering effect in
regard to demarcating a clear threshold, although there are many
studies which disagree with this evidence.
The existence of multiple Low-T
Thresholds provides evidence for the concept that different symptoms
are correlated with different thresholds because Testosterone is
bio-available and biologically functional at different concentrations
dependent upon the location and biology of different receptor sites.
Although the three primary sexual symptoms of Adult-Onset
Testosterone Deficiency are loosely correlated in terms of threshold,
it is possible to clearly separate the clustering of these three
symptoms, showing a different base level of Testosterone associated
with each individual symptom.
The outer boundaries that led these
researchers to conclude a significant correlation between Low-T and
the symptoms of the disorder are considered by the researchers to be
the minimal criteria in order to diagnose Adult-Onset Hypogonadism
with near 100% accuracy. The Threshold Testosterone levels discovered
in this study (11 nanomoles per liter Total Testosterone and 220
picomoles per liter Free Testosterone) are very similar to minimum
diagnosis criteria suggested by general medical guidelines.
Again, there are a number of
confounding factors which increase the risk and prevalence of
Testosterone Deficiency, making it more common than the percentages
listed earlier imply. The symptoms of Adult-Onset Hypogonadism are
complicated significantly be the presence of other medical issues. In
addition to this, endogenous Testosterone levels become suppressed by
a number of physiological factors such as obesity as well.
Previous EMAS Testosterone Study
In a previous medical study released
by the authors of this journal article, the researchers again used
the data from the EMAS study in order to learn more about the complex
physiological pathology of Adult-Onset Hypogonadism. In this previous
study, the researchers simply evaluated the participants of the EMAS
study based upon Biochemical Testosterone Deficiency, categorizing
such deficiency as compensated, primary, or secondary.
In this study, the researchers
ignored physiological symptoms of Low Testosterone and simply grouped
patients dependent upon the form of hypogonadism they experienced. If
one ignores symptoms and only considered Biologically Low
Testosterone, 23.3% of males could be clinically diagnosed with
Testosterone Deficiency. The purpose of the initial study was simply
theoretical knowledge seeking, whereas this study is an attempt to
apply that scientific knowledge in an attempt to greater understand
and streamline medical diagnosis and treatment of Testosterone
Deficiency.
Counterpoint to Clinical Study
This study claims with seemingly
unwavering confidence that only 2.1% of males experience Adult-Onset
Hypogonadism. They claim that this study emphasizes the important of
not only chemically diagnosing Adult-Onset Hypogonadism but also
taking into account the fact that only patients who experienced
negative symptoms as a result of Testosterone Deficiency are truly in
need of the treatment.
Although we recognize the value and
benefit of a study such as this, we are slightly incredulous at the
confidence in the author's overarching claims. Although it may be
true that only 2.1% of otherwise completely healthy males experience
Testosterone Deficiency, this does not seem to properly take into
account the variety of disorders such as Diabetes, Obesity, and
Sedentary Lifestyle which greatly increase the odds of suffering from
Testosterone Deficiency by a significant amount.
Also, the study does not consider the
fact the different patients may have different biological needs for
Testosterone. It would make logical sense that sexuality and sexual
function are tightly and neatly correlated with specific Testosterone
levels, but many issues such as anxiety or depression may not always
be the direct result of Low-Testosterone, though they may be greatly
alleviated by Testosterone Replacement.
Low-T is Rife with Non-Specific
Symptoms
The extended list on non-specific
symptoms of Testosterone Deficiency make it hard to construct hard
guidelines regarding the diagnosis of Adult-Onset Hypogonadism. For
this reason, even the rate at which the primarily sexual symptoms of
Testosterone Deficiency occurred was moderately high among males with
unquestionably normal Testosterone Levels. With non-specific
disorders such as Testosterone Deficiency, it is utterly important to
only diagnose Low-T when a patient is experiencing three or more
relatively clear symptoms of the disorder. Combining this diagnostic
rule of thumb with accurate Testosterone Testing helps ensure that a
proper diagnosis is ultimately made.
This study also shows that Total
Testosterone Levels are a more useful indicator of Testosterone
Deficiency than Free Testosterone Levels. Although in most cases,
Total Testosterone may be enough to diagnose the majority of
patients, Free Testosterone Analysis can help a physician make a more
accurate diagnosis in the incidence of a complex case or when Total
Testosterone Levels are discovered to be borderline.
Testosterone HRT and the Conscious
Evolution Institute
Testosterone Hormone Replacement
Therapy is a valuable potential treatment option for any man over the
age of thirty who feels that they may be suffering from the symptoms
of Testosterone Deficiency. We at the Conscious Evolution Institute
feel that this study increases our knowledge about Male Hypogonadism
in spite of its cautious and tentative nature.
We feel that any study which more
clearly defines what Clinical Testosterone Deficiency is incredibly
beneficial to the international medical body of knowledge, but we
understand that Testosterone Deficiency is a complex disorder which
has the capacity to effect different men in significantly different
ways. If you have any questions about this study or have any other
questions regarding Hormone Replacement Therapy featuring
Testosterone or any other Hormone Treatment we provide, we encourage
you to reach out and contact the Conscious Evolution Institute today!
We
recommend
