ExcelMale
Menu
Home
What's new
Latest activity
Forums
New posts
Search forums
What's new
New posts
Latest activity
Videos
Lab Tests
Doctor Finder
Buy Books
About Us
Men’s Health Coaching
Log in
Register
What's new
Search
Search
Search titles only
By:
New posts
Search forums
Menu
Log in
Register
Navigation
Install the app
Install
More options
Contact us
Close Menu
Forums
Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Testosterone Deficiency in Men
JavaScript is disabled. For a better experience, please enable JavaScript in your browser before proceeding.
You are using an out of date browser. It may not display this or other websites correctly.
You should upgrade or use an
alternative browser
.
Reply to thread
Message
<blockquote data-quote="madman" data-source="post: 215924" data-attributes="member: 13851"><p><em><strong>*In the diagnostic evaluation of men who present with symptoms suggestive of testosterone deficiency,1,9 the</strong> <strong>first step</strong> <strong>is to ascertain symptoms and perform a general health evaluation to exclude the possibility of a systemic illness, such as cancer, chronic infection, or inflammatory disorder; body image and eating disorders; excessive physical exercise; or the use of medications, such as opioids, glucocorticoids, androgenic anabolic steroids, or other medications that inhibit testosterone’s production, action, or bioavailability (Fig.1)</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*The second step is to measure total testosterone concentration and, if indicated, free testosterone concentration using reliable assays of blood samples obtained in the morning after an overnight fast</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Nonspecificity of symptoms and signs, variations in testosterone levels over time due to biologic factors, imprecision and inaccuracy in the measurement of total and free testosterone concentrations, variations in binding protein concentrations, and suboptimal reference ranges contribute to diagnostic inaccuracies</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*<em><strong>Diurnal, circadian, and circannual rhythms and episodic secretion contribute to a variation in testosterone concentrations.21,23,24 Testosterone concentrations exhibit a diurnal variation, with peak values in the morning; this diurnal rhythm is dampened in older men.23 Testosterone concentrations are suppressed by food intake25,26 and during an acute illness.</strong> <strong>Therefore, testosterone concentrations should be measured after an overnight fast, typically within 4 to 5 hours after waking up in the morning</strong></em></strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Free testosterone concentration is ideally measured using the equilibrium dialysis method, performed under standardized conditions.1,31 </strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Direct tracer analog methods for measuring free testosterone concentrations are inaccurate, and therefore, their use is not recommended.35</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*equations that are based on a linear model of testosterone’s binding to SHBG assume a fixed binding affinity (approximately 1 nM)31 and ignore the competing presence of other sex steroids, such as dihydrotestosterone and estradiol</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Recent studies using modern biophysical techniques have suggested that the binding of testosterone and estradiol to an SHBG dimer is a dynamic process that involves allosteric interactions between binding sites on each of the 2 SHBG monomers such that the binding affinities of the 2 sites are not equivalent.36,39</strong> <strong>The binding of a ligand to the first monomer influences the conformational and energetic states of both the monomers.39 The estimation of free testosterone concentration based on an ensemble allosteric model provides a close approximation of concentrations measured using equilibrium dialysis36;</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*the computations of free testosterone concentrations using the ensemble allostery model can be obtained at <a href="https://tru-t.org/" target="_blank">TruT Free Testosterone Calculator by FPT</a></strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Because of dynamic changes in the binding affinity of SHBG upon ligand binding, depending on the ligand and SHBG concentrations, no equation can accurately estimate free testosterone concentration under all conditions.39</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Platform-based immunoassays offer convenience and rapid throughput but suffer from inaccuracy, especially for a low range of testosterone concentration, which is prevalent in hypogonadal men</strong></em><strong><em>.35,41</em></strong><em> </em></p><p><em></em></p><p><em><strong>*Liquid chromatography-tandem mass spectrometry assays have emerged as the method of choice, with the highest accuracy and precision for the measurement of total testosterone concentration, and are now widely available.</strong></em></p><p><em><strong></strong></em></p><p><em><strong><strong>*With the establishment of a process for accuracy-based certification of laboratories by the Center f</strong>or Disease Control and Prevention’s (CDC) hormone standardization program for testosterone, interlaboratory variation in CDC-certified laboratories has decreased substantially.42,43</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*A harmonized reference range for total testosterone was generated based on analyses of data from 4 cohorts of community-dwelling men in the United States and Europe.44 The assays used in these 4 cohorts were cross-calibrated against a higher-order method by the CDC, and the values from each cohort were harmonized to the CDC-standardized measurements using Deming regression. The harmonized reference range for the total testosterone concentration in healthy non-obese men, aged 19 to 39 years, was 264 to 916 ng/dL using the 2.5th and 97.5th percentiles and 303 to 852 ng/dL using the 5th and 95th percentiles44; the age-specific 2.5th, 5th, 95th, and 97.5th percentile reference values are shown in Table 2. </strong></em></p><p><em><strong></strong></em></p><p><em><strong>*These reference values can be used for all testosterone assays and laboratories that are certified by the CDC’s hormone standardization program for testosterone</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*<em><strong>The lack of standardization of the equilibrium dialysis procedures for the measurement of free testosterone has retarded efforts at generating harmonized reference ranges.35 </strong></em></strong></em></p><p><em><strong><em><strong></strong></em></strong></em></p><p><em><strong><em><strong>*A reference range for free testosterone, using an ensemble allostery method that was validated against the equilibrium dialysis method using data from the Framingham Heart Study and the European Male Aging Study, has been published.36</strong></em></strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Biotin supplements can interfere with some LH and FSH assays; therefore, these supplements should be stopped at least 3 days before the blood test depending on how much biotin the patient is taking</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Testosterone therapy is associated with increased risk of harm in patients who have breast or prostate cancer; a palpable prostate nodule or induration; a prostate-specific antigen level of >3ng/mL without a further urologic evaluation; elevated hematocrit; untreated severe obstructive sleep apnea; severe lower urinary tract symptoms; uncontrolled heart failure, myocardial infarction, or stroke within the last 6 months; or thrombophilia and should not be given to such patients.1</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Prostate cancer screening has some risks; therefore, the decision to perform prostate cancer screening should be a shared decision of the patient and the clinician</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Clinicians should consider testosterone treatment in men with opioid-associated hypogonadism who have sexual symptoms, unexplained anemia, osteoporosis, and in whom the discontinuation of opioid medication seems unlikely.1</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*The adverse effects associated with testosterone treatment include erythrocytosis, acne, breast tenderness, leg edema, suppression of spermatogenesis; and formulation-specific adverse effects, such as injection site pain and pulmonary oil microembolism reactions with intramuscular testosterone esters, local skin reactions, and the risk of transfer with transdermal gel formulations.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Erythrocytosis is the most frequent adverse event associated with testosterone treatment, but the frequency of neuro-occlusive events was very low in the randomized trials</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Testosterone treatment can cause transient salt and water retention and may exacerbate heart failure in patients with heart failure</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Testosterone treatment does not worsen lower urinary tract symptoms in men with testosterone deficiency who do not have severe lower urinary tract symptoms prior to treatment.53,75</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Testosterone treatment did not affect the rate of atherosclerosis progression, assessed using common carotid artery intima-media thickness or coronary calcium scores; in the Cardiovascular Trial of the TTrials,76 which enrolled men with hypogonadism, aged ≥65 years, or in the Testosterone Effects on Atherosclerosis in Aging Men trial, which enrolled men, aged ≥60 years, with low or low-to-normal testosterone levels.77 </strong></em></p><p><em><strong></strong></em></p><p><em><strong>*In the Cardiovascular Trial of the TTrials,76 testosterone treatment was associated with a significantly greater increase in noncalcified plaque volume in the coronary arteries from baseline to 12 months, measured using computed tomography angiography; however, the clinical significance of the increase in the noncalcified plaque volume remains unclear.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>* No trial has been long enough or large enough to determine the long-term risk of major adverse cardiovascular events or prostate cancer during testosterone treatment.66</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*An ongoing large cardiovascular safety trial (TRAVERSE trial, NCT NCT03518034) is evaluating the effects of testosterone treatment on major adverse cardiovascular events for up to 5 years in men, aged 45 to 80 years, with hypogonadism.</strong></em></p></blockquote><p></p>
[QUOTE="madman, post: 215924, member: 13851"] [I][B]*In the diagnostic evaluation of men who present with symptoms suggestive of testosterone deficiency,1,9 the[/B] [B]first step[/B] [B]is to ascertain symptoms and perform a general health evaluation to exclude the possibility of a systemic illness, such as cancer, chronic infection, or inflammatory disorder; body image and eating disorders; excessive physical exercise; or the use of medications, such as opioids, glucocorticoids, androgenic anabolic steroids, or other medications that inhibit testosterone’s production, action, or bioavailability (Fig.1) *The second step is to measure total testosterone concentration and, if indicated, free testosterone concentration using reliable assays of blood samples obtained in the morning after an overnight fast *Nonspecificity of symptoms and signs, variations in testosterone levels over time due to biologic factors, imprecision and inaccuracy in the measurement of total and free testosterone concentrations, variations in binding protein concentrations, and suboptimal reference ranges contribute to diagnostic inaccuracies *[I][B]Diurnal, circadian, and circannual rhythms and episodic secretion contribute to a variation in testosterone concentrations.21,23,24 Testosterone concentrations exhibit a diurnal variation, with peak values in the morning; this diurnal rhythm is dampened in older men.23 Testosterone concentrations are suppressed by food intake25,26 and during an acute illness.[/B] [B]Therefore, testosterone concentrations should be measured after an overnight fast, typically within 4 to 5 hours after waking up in the morning[/B][/I] *Free testosterone concentration is ideally measured using the equilibrium dialysis method, performed under standardized conditions.1,31 *Direct tracer analog methods for measuring free testosterone concentrations are inaccurate, and therefore, their use is not recommended.35 *equations that are based on a linear model of testosterone’s binding to SHBG assume a fixed binding affinity (approximately 1 nM)31 and ignore the competing presence of other sex steroids, such as dihydrotestosterone and estradiol *Recent studies using modern biophysical techniques have suggested that the binding of testosterone and estradiol to an SHBG dimer is a dynamic process that involves allosteric interactions between binding sites on each of the 2 SHBG monomers such that the binding affinities of the 2 sites are not equivalent.36,39[/B] [B]The binding of a ligand to the first monomer influences the conformational and energetic states of both the monomers.39 The estimation of free testosterone concentration based on an ensemble allosteric model provides a close approximation of concentrations measured using equilibrium dialysis36; *the computations of free testosterone concentrations using the ensemble allostery model can be obtained at [URL='https://tru-t.org/']TruT Free Testosterone Calculator by FPT[/URL] *Because of dynamic changes in the binding affinity of SHBG upon ligand binding, depending on the ligand and SHBG concentrations, no equation can accurately estimate free testosterone concentration under all conditions.39 *Platform-based immunoassays offer convenience and rapid throughput but suffer from inaccuracy, especially for a low range of testosterone concentration, which is prevalent in hypogonadal men[/B][/I][B][I].35,41[/I][/B][I] [B]*Liquid chromatography-tandem mass spectrometry assays have emerged as the method of choice, with the highest accuracy and precision for the measurement of total testosterone concentration, and are now widely available. [B]*With the establishment of a process for accuracy-based certification of laboratories by the Center f[/B]or Disease Control and Prevention’s (CDC) hormone standardization program for testosterone, interlaboratory variation in CDC-certified laboratories has decreased substantially.42,43 *A harmonized reference range for total testosterone was generated based on analyses of data from 4 cohorts of community-dwelling men in the United States and Europe.44 The assays used in these 4 cohorts were cross-calibrated against a higher-order method by the CDC, and the values from each cohort were harmonized to the CDC-standardized measurements using Deming regression. The harmonized reference range for the total testosterone concentration in healthy non-obese men, aged 19 to 39 years, was 264 to 916 ng/dL using the 2.5th and 97.5th percentiles and 303 to 852 ng/dL using the 5th and 95th percentiles44; the age-specific 2.5th, 5th, 95th, and 97.5th percentile reference values are shown in Table 2. *These reference values can be used for all testosterone assays and laboratories that are certified by the CDC’s hormone standardization program for testosterone *[I][B]The lack of standardization of the equilibrium dialysis procedures for the measurement of free testosterone has retarded efforts at generating harmonized reference ranges.35 *A reference range for free testosterone, using an ensemble allostery method that was validated against the equilibrium dialysis method using data from the Framingham Heart Study and the European Male Aging Study, has been published.36[/B][/I] *Biotin supplements can interfere with some LH and FSH assays; therefore, these supplements should be stopped at least 3 days before the blood test depending on how much biotin the patient is taking *Testosterone therapy is associated with increased risk of harm in patients who have breast or prostate cancer; a palpable prostate nodule or induration; a prostate-specific antigen level of >3ng/mL without a further urologic evaluation; elevated hematocrit; untreated severe obstructive sleep apnea; severe lower urinary tract symptoms; uncontrolled heart failure, myocardial infarction, or stroke within the last 6 months; or thrombophilia and should not be given to such patients.1 *Prostate cancer screening has some risks; therefore, the decision to perform prostate cancer screening should be a shared decision of the patient and the clinician *Clinicians should consider testosterone treatment in men with opioid-associated hypogonadism who have sexual symptoms, unexplained anemia, osteoporosis, and in whom the discontinuation of opioid medication seems unlikely.1 *The adverse effects associated with testosterone treatment include erythrocytosis, acne, breast tenderness, leg edema, suppression of spermatogenesis; and formulation-specific adverse effects, such as injection site pain and pulmonary oil microembolism reactions with intramuscular testosterone esters, local skin reactions, and the risk of transfer with transdermal gel formulations. *Erythrocytosis is the most frequent adverse event associated with testosterone treatment, but the frequency of neuro-occlusive events was very low in the randomized trials *Testosterone treatment can cause transient salt and water retention and may exacerbate heart failure in patients with heart failure *Testosterone treatment does not worsen lower urinary tract symptoms in men with testosterone deficiency who do not have severe lower urinary tract symptoms prior to treatment.53,75 *Testosterone treatment did not affect the rate of atherosclerosis progression, assessed using common carotid artery intima-media thickness or coronary calcium scores; in the Cardiovascular Trial of the TTrials,76 which enrolled men with hypogonadism, aged ≥65 years, or in the Testosterone Effects on Atherosclerosis in Aging Men trial, which enrolled men, aged ≥60 years, with low or low-to-normal testosterone levels.77 *In the Cardiovascular Trial of the TTrials,76 testosterone treatment was associated with a significantly greater increase in noncalcified plaque volume in the coronary arteries from baseline to 12 months, measured using computed tomography angiography; however, the clinical significance of the increase in the noncalcified plaque volume remains unclear. * No trial has been long enough or large enough to determine the long-term risk of major adverse cardiovascular events or prostate cancer during testosterone treatment.66 *An ongoing large cardiovascular safety trial (TRAVERSE trial, NCT NCT03518034) is evaluating the effects of testosterone treatment on major adverse cardiovascular events for up to 5 years in men, aged 45 to 80 years, with hypogonadism.[/B][/I] [/QUOTE]
Insert quotes…
Verification
Post reply
Share this page
Facebook
Twitter
Reddit
Pinterest
Tumblr
WhatsApp
Email
Share
Link
Sponsors
Forums
Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Testosterone Deficiency in Men
This site uses cookies to help personalise content, tailor your experience and to keep you logged in if you register.
By continuing to use this site, you are consenting to our use of cookies.
Accept
Learn more…
Top