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
When Testosterone Is Not Enough
Long-term treatment of ED: beyond the purely symptomatic use of PDE5I
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: 193160" data-attributes="member: 13851"><p><strong>Testosterone</strong></p><p><strong></strong></p><p><strong><u><em>Testosterone was isolated in the 1930s and defined as an important male sex hormone</em></u><em>.55 </em></strong><em>Different formations of testosterone have been used clinically since the end of the 1930s.55 <strong><u>Despite its familiarity and clinical use, there have been controversial and extensive scientific and medical discussions about the physiological effects and clinical effects of this sex hormone</u>. </strong>This ongoing, controversial discussion has prompted the Basic Science Committee of the Sexual Medicine Society of North America in 2016 to undertake a comprehensive review of the scientific, evidence-based data on the role of testosterone in sexual function and dysfunction.56 <strong>The conclusion of this review (written by John Mulhall) paints a very sobering picture with regard to the basic scientific results available at that time: “<u>There is no doubt that the approach to diagnosing and treating men with testosterone deficiency in the early 21st century is extremely crude- .Indeed, in practice, much of what we do falls under the banner of trial and error</u>.” 56</strong> This judgment of Mulhall was a consequence of the fact that many scientific results concerning testosterone were generated from in vitro studies, found in animal models, and/or demonstrated on other tissues and in many cases, only indirect conclusions could be drawn about the physiological and pathological situation in humans.<strong> <u>Mulhall concluded by saying that he was very confident that he will be able to present better data on basic testosterone research in 2025</u>.56 </strong>In light of this sobering statement, the following comments on the influence of testosterone on the physiology and pathology of an erection and the erectile mechanism of the penis should be used with caution.</em></p><p><em></em></p><p><em><strong><u>With regard to the influence of testosterone on the erectile function of the penis, scientific studies essentially focus on the support of the tissue architecture of the erectile tissue, regulation of the tone of the smooth muscles as well as the influence on NO and cGMP regulation</u>.</strong> Many research groups were able to show that androgen deprivation leads to typical changes in the erectile tissue. In endothelial cells, the androgen deprivation provokes an irregular surface and an impairment of cell-cell contacts, which leads to permeability and adhesion of erythrocytes on the endothelial cell surface.57 Under the administration of testosterone these morphological changes are largely regressive.57 In addition, a reduction of smooth muscle cells, and an increase in extracellular matrix and adipocytes in the cavernous body tissue were observed.58,59 <strong><u>All these processes are considered to be degenerative and function-limiting</u>. <u>The tone of the muscle cells in penile vessels and the trabeculae of the sinusoids are largely responsible for the flaccidity and erection of the penis</u>. <u>As already explained (see above), an erection is based on a complex molecular and fine anatomical interaction</u>. <u>Scientific studies have shown that testosterone has a supportive effect at various points in this complex interaction</u>. For example, testosterone appears to stimulate and support the enzyme activity of nitrogen synthase (NOS), which is probably one of the most important molecular effects of testosterone in supporting the erection mechanism.60 Furthermore, testosterone regulates the gene expression of many molecules related to the erectile mechanism (eg, nNOS, phosphodiesterase 5, alpha1-adrenoreceptor, etc).56 Additionally, there appears to be some direct effect of testosterone on muscle tone in erectile tissue. For example, the testosterone concentration present in the cavernous body (normal or at castration level) directly influences the response of the muscle cells to norepinephrine (contraction) in such a way that under locally lower testosterone concentration the muscle cells react much faster to norepinephrine with a contraction (and thus flaccidity of the penis).61 <u>In this respect, there are numerous indications of a direct and indirect influence of testosterone on erection</u>. </strong>However, the objection formulated by Mulhall, which is easily understandable from the literature, still exists that the scientific findings were not made on human erectile tissue. For our clinical examination, however, the basic results are only of secondary importance.<strong> <u>For the clinical application of testosterone in the context of the treatment of erectile dysfunction, high-quality clinical studies (set up in the light of basic scientific findings) are necessary</u>. <u>The European Male Aging Study was able to clearly show on more than 3,400 men that erectile dysfunction is the most sensitive and specific indicator of a testosterone deficiency</u>.62 <u>In this respect, a clinical influence of the testosterone deficiency on erection can be assumed</u>.</strong> Unfortunately, the quality of the investigations in this field is also mostly not optimal, so that inconsistent results are available. A major disadvantage of many investigations is the use of different measuring instruments with regard to the therapeutic outcome. Often simple patient statements are defined as the final result of a study. This is all the more incomprehensible as the IIEF has been available for many years as a validated and reproducible instrument for measuring the results of erectile dysfunction treatments.63 <strong><u>Most meta-analyses show a positive effect of testosterone therapy on erectile function</u>.64e66 <u>However, other major review studies do not confirm these findings</u>.67,68 </strong>Corona and colleagues responded by including in the most recent meta-analysis only randomized and controlled studies (137 studies examined and 14 included) that used the IIEF score as an endpoint measurement tool.69 Here, it could be shown once again, on a total of 2,298 patients included, that testosterone therapy (among other effects) is also an effective therapeutic agent for erectile dysfunction in men with testosterone deficiency. Depending on the severity of the testosterone deficiency (<12 nmol/L or <8 nmol/L), significant improvements in the IIEF score (1.47 and 2.95, a total of 2.31 points) were shown compared to the placebo group. However, according to the investigators, the observed overall effect of 2.31 points improvement in IIEF-ED under testosterone therapy only represents a clinically relevant improvement in patients with mild erectile dysfunction.69,70 <strong><u>In summary, it can therefore be stated that especially in patients with a pronounced testosterone deficiency (<8 nmol/L) and a mild erectile dysfunction, a primary attempt can be made to treat both disorders with testosterone replacement therapy</u>. <u>It should be noted with limitations that metabolic conditions such as obesity and diabetes mellitus worsen the response</u>.69</strong></em></p><p><em></em></p><p><em>Of particular importance to us is the clear effect of testosterone replacement therapy as a strong supporter of physical activity, which (as described earlier) has a clearly positive effect on erectile performance.40</em></p><p><em></em></p><p><em>Of equal interest is the possible inducibility of the body's own testosterone production by vitamin D (see also below). A study by Pilz and colleagues showed that 165 patients who received 83 mg (3,332 IU) of vitamin D daily had a significantly higher testosterone level after 1 year than at the beginning of the study. The placebo group showed no change in testosterone levels.71 Other studies could not show a correlation between vitamin D supplementation and testosterone serum concentration.72,73 However, the application periods of 12-16 weeks were significantly shorter.</em></p><p><em></em></p><p><em></em></p><p><strong><em>*We believe that an external supply of testosterone may be a primary treatment option in cases where mild erectile dysfunction coincides with testosterone deficiency. In cases of severe erectile dysfunction and testosterone deficiency, combination therapy (eg, testosterone plus lifestyle modification, and/or additional medication) should be used. The delayed time frame until the benefit of testosterone replacement therapy must be pointed out.</em></strong></p></blockquote><p></p>
[QUOTE="madman, post: 193160, member: 13851"] [B]Testosterone [U][I]Testosterone was isolated in the 1930s and defined as an important male sex hormone[/I][/U][I].55 [/I][/B][I]Different formations of testosterone have been used clinically since the end of the 1930s.55 [B][U]Despite its familiarity and clinical use, there have been controversial and extensive scientific and medical discussions about the physiological effects and clinical effects of this sex hormone[/U]. [/B]This ongoing, controversial discussion has prompted the Basic Science Committee of the Sexual Medicine Society of North America in 2016 to undertake a comprehensive review of the scientific, evidence-based data on the role of testosterone in sexual function and dysfunction.56 [B]The conclusion of this review (written by John Mulhall) paints a very sobering picture with regard to the basic scientific results available at that time: “[U]There is no doubt that the approach to diagnosing and treating men with testosterone deficiency in the early 21st century is extremely crude- .Indeed, in practice, much of what we do falls under the banner of trial and error[/U].” 56[/B] This judgment of Mulhall was a consequence of the fact that many scientific results concerning testosterone were generated from in vitro studies, found in animal models, and/or demonstrated on other tissues and in many cases, only indirect conclusions could be drawn about the physiological and pathological situation in humans.[B] [U]Mulhall concluded by saying that he was very confident that he will be able to present better data on basic testosterone research in 2025[/U].56 [/B]In light of this sobering statement, the following comments on the influence of testosterone on the physiology and pathology of an erection and the erectile mechanism of the penis should be used with caution. [B][U]With regard to the influence of testosterone on the erectile function of the penis, scientific studies essentially focus on the support of the tissue architecture of the erectile tissue, regulation of the tone of the smooth muscles as well as the influence on NO and cGMP regulation[/U].[/B] Many research groups were able to show that androgen deprivation leads to typical changes in the erectile tissue. In endothelial cells, the androgen deprivation provokes an irregular surface and an impairment of cell-cell contacts, which leads to permeability and adhesion of erythrocytes on the endothelial cell surface.57 Under the administration of testosterone these morphological changes are largely regressive.57 In addition, a reduction of smooth muscle cells, and an increase in extracellular matrix and adipocytes in the cavernous body tissue were observed.58,59 [B][U]All these processes are considered to be degenerative and function-limiting[/U]. [U]The tone of the muscle cells in penile vessels and the trabeculae of the sinusoids are largely responsible for the flaccidity and erection of the penis[/U]. [U]As already explained (see above), an erection is based on a complex molecular and fine anatomical interaction[/U]. [U]Scientific studies have shown that testosterone has a supportive effect at various points in this complex interaction[/U]. For example, testosterone appears to stimulate and support the enzyme activity of nitrogen synthase (NOS), which is probably one of the most important molecular effects of testosterone in supporting the erection mechanism.60 Furthermore, testosterone regulates the gene expression of many molecules related to the erectile mechanism (eg, nNOS, phosphodiesterase 5, alpha1-adrenoreceptor, etc).56 Additionally, there appears to be some direct effect of testosterone on muscle tone in erectile tissue. For example, the testosterone concentration present in the cavernous body (normal or at castration level) directly influences the response of the muscle cells to norepinephrine (contraction) in such a way that under locally lower testosterone concentration the muscle cells react much faster to norepinephrine with a contraction (and thus flaccidity of the penis).61 [U]In this respect, there are numerous indications of a direct and indirect influence of testosterone on erection[/U]. [/B]However, the objection formulated by Mulhall, which is easily understandable from the literature, still exists that the scientific findings were not made on human erectile tissue. For our clinical examination, however, the basic results are only of secondary importance.[B] [U]For the clinical application of testosterone in the context of the treatment of erectile dysfunction, high-quality clinical studies (set up in the light of basic scientific findings) are necessary[/U]. [U]The European Male Aging Study was able to clearly show on more than 3,400 men that erectile dysfunction is the most sensitive and specific indicator of a testosterone deficiency[/U].62 [U]In this respect, a clinical influence of the testosterone deficiency on erection can be assumed[/U].[/B] Unfortunately, the quality of the investigations in this field is also mostly not optimal, so that inconsistent results are available. A major disadvantage of many investigations is the use of different measuring instruments with regard to the therapeutic outcome. Often simple patient statements are defined as the final result of a study. This is all the more incomprehensible as the IIEF has been available for many years as a validated and reproducible instrument for measuring the results of erectile dysfunction treatments.63 [B][U]Most meta-analyses show a positive effect of testosterone therapy on erectile function[/U].64e66 [U]However, other major review studies do not confirm these findings[/U].67,68 [/B]Corona and colleagues responded by including in the most recent meta-analysis only randomized and controlled studies (137 studies examined and 14 included) that used the IIEF score as an endpoint measurement tool.69 Here, it could be shown once again, on a total of 2,298 patients included, that testosterone therapy (among other effects) is also an effective therapeutic agent for erectile dysfunction in men with testosterone deficiency. Depending on the severity of the testosterone deficiency (<12 nmol/L or <8 nmol/L), significant improvements in the IIEF score (1.47 and 2.95, a total of 2.31 points) were shown compared to the placebo group. However, according to the investigators, the observed overall effect of 2.31 points improvement in IIEF-ED under testosterone therapy only represents a clinically relevant improvement in patients with mild erectile dysfunction.69,70 [B][U]In summary, it can therefore be stated that especially in patients with a pronounced testosterone deficiency (<8 nmol/L) and a mild erectile dysfunction, a primary attempt can be made to treat both disorders with testosterone replacement therapy[/U]. [U]It should be noted with limitations that metabolic conditions such as obesity and diabetes mellitus worsen the response[/U].69[/B] Of particular importance to us is the clear effect of testosterone replacement therapy as a strong supporter of physical activity, which (as described earlier) has a clearly positive effect on erectile performance.40 Of equal interest is the possible inducibility of the body's own testosterone production by vitamin D (see also below). A study by Pilz and colleagues showed that 165 patients who received 83 mg (3,332 IU) of vitamin D daily had a significantly higher testosterone level after 1 year than at the beginning of the study. The placebo group showed no change in testosterone levels.71 Other studies could not show a correlation between vitamin D supplementation and testosterone serum concentration.72,73 However, the application periods of 12-16 weeks were significantly shorter. [/I] [B][I]*We believe that an external supply of testosterone may be a primary treatment option in cases where mild erectile dysfunction coincides with testosterone deficiency. In cases of severe erectile dysfunction and testosterone deficiency, combination therapy (eg, testosterone plus lifestyle modification, and/or additional medication) should be used. The delayed time frame until the benefit of testosterone replacement therapy must be pointed out.[/I][/B] [/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
When Testosterone Is Not Enough
Long-term treatment of ED: beyond the purely symptomatic use of PDE5I
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