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<blockquote data-quote="Jerajera" data-source="post: 240866" data-attributes="member: 40995"><p>[USER=38590]@readalot[/USER] posted some studies in this thread: <a href="https://www.excelmale.com/forum/threads/trans-scrotal-testosterone-cream-application-is-a-game-changer.19658/page-9" target="_blank">Trans scrotal testosterone cream application is a game changer</a></p><p></p><p>There's an interesting back and forth between Dr Saya and [USER=42893]@RobRoy[/USER], who I think was understood to be Dr Nichols.</p><p></p><p>This is the most comprehensive study I've seen on DHT (on or off TRT), I recommend reading it: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459338/" target="_blank">Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels</a></p><p></p><h3>Essential Points</h3> <ul> <li data-xf-list-type="ul">Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not correlate with those found in androgen sensitive tissue (e.g., prostate, adipose, muscle) due to local regulatory mechanisms that tightly control intracellular androgen homeostasis.</li> <li data-xf-list-type="ul">The modest increases observed in serum DHT and in the DHT/T ratio observed after TRT are unlikely to be a cause of clinical concern, particularly when viewed in the context of changes observed in these parameters for currently marketed T-replacement products and those under development for which DHT data are available.</li> <li data-xf-list-type="ul">While well-controlled, long-term studies designed to specifically examine the effects of androgen exposure on risk for prostate need to be conducted, the current clinical data base is relatively reassuring that circulating levels of androgens (or changes in such) apparently do not play as pivotal a role as once thought in the development of prostate disease.</li> <li data-xf-list-type="ul">Robust epidemiologic or clinical trial evidence of a deleterious DHT effect on CVD is lacking. There is some evidence that DHT therapy in men with CVD may improve clinical status—a finding that needs confirmation. Data from a longitudinal data base of older normal (i.e., not hypogonadal) indicated an association between serum DHT and incident CV disease and mortality. Conversely, others have reported that higher DHT levels in older men were associated with decreased all-cause mortality and reduced ischemic heart disease mortality. Additional exploration in prospective, placebo-controlled intervention studies of TRT with CVD as the primary endpoint is needed to resolve the long-term effects of androgens on CVD risks.</li> <li data-xf-list-type="ul">DHT does not play a substantive role in body composition compared to T under normal conditions. Thus, elevated levels of DHT in response to TRT are unlikely to appreciably impact lean or fat mass. Nonetheless, data from animals suggest a role for DHT in adipose tissue that inhibits biochemical pathways involved in lipid synthesis and promotes several transcripts associated with apoptosis of adipocytes. Whether these DHT-induced effects also occur in human adipose tissue remains an area for future study.</li> <li data-xf-list-type="ul">There is very limited data available regarding DHT and effects on cognition. Further research is needed, particularly in light of animal data where DHT positively modified synaptic structure and significantly delayed cognitive impairment in a well-regarded animal model for Alzheimer’s disease.</li> <li data-xf-list-type="ul">Recent data indicating that higher levels of DHT were inversely associated with insulin resistance and risk of diabetes merit further mechanistic investigation to understand whether this action is separate from that of T.</li> </ul><p></p><p>There was a study showing extremely elevated DHT levels (around 500+ ng/dL) for I think 24 months without negative side effects (along the specific markers and metrics they were keeping track of of course). However in that study Testosterone wasn't supplemented and therefore Test levels fell and were severely depressed throughout the study, so those findings don't necessarily represent what hyper-elevated DHT levels would do to someone on TRT long term.</p><p></p><p>In general negative side effects as a function of hormone levels follow a classic "u" curve, whereby too low or too high levels lead to dose-dependent increased negative sides. Just because there isn't research showing those negative side effects doesn't mean they won't happen. </p><p></p><p>At some point, in the absence of specific enough research I think common sense should prevail and to me, that means running DHT at 5-10x the range for a few decades is probably a bad idea</p></blockquote><p></p>
[QUOTE="Jerajera, post: 240866, member: 40995"] [USER=38590]@readalot[/USER] posted some studies in this thread: [URL="https://www.excelmale.com/forum/threads/trans-scrotal-testosterone-cream-application-is-a-game-changer.19658/page-9"]Trans scrotal testosterone cream application is a game changer[/URL] There's an interesting back and forth between Dr Saya and [USER=42893]@RobRoy[/USER], who I think was understood to be Dr Nichols. This is the most comprehensive study I've seen on DHT (on or off TRT), I recommend reading it: [URL="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459338/"]Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels[/URL] [HEADING=2]Essential Points[/HEADING] [LIST] [*]Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not correlate with those found in androgen sensitive tissue (e.g., prostate, adipose, muscle) due to local regulatory mechanisms that tightly control intracellular androgen homeostasis. [*]The modest increases observed in serum DHT and in the DHT/T ratio observed after TRT are unlikely to be a cause of clinical concern, particularly when viewed in the context of changes observed in these parameters for currently marketed T-replacement products and those under development for which DHT data are available. [*]While well-controlled, long-term studies designed to specifically examine the effects of androgen exposure on risk for prostate need to be conducted, the current clinical data base is relatively reassuring that circulating levels of androgens (or changes in such) apparently do not play as pivotal a role as once thought in the development of prostate disease. [*]Robust epidemiologic or clinical trial evidence of a deleterious DHT effect on CVD is lacking. There is some evidence that DHT therapy in men with CVD may improve clinical status—a finding that needs confirmation. Data from a longitudinal data base of older normal (i.e., not hypogonadal) indicated an association between serum DHT and incident CV disease and mortality. Conversely, others have reported that higher DHT levels in older men were associated with decreased all-cause mortality and reduced ischemic heart disease mortality. Additional exploration in prospective, placebo-controlled intervention studies of TRT with CVD as the primary endpoint is needed to resolve the long-term effects of androgens on CVD risks. [*]DHT does not play a substantive role in body composition compared to T under normal conditions. Thus, elevated levels of DHT in response to TRT are unlikely to appreciably impact lean or fat mass. Nonetheless, data from animals suggest a role for DHT in adipose tissue that inhibits biochemical pathways involved in lipid synthesis and promotes several transcripts associated with apoptosis of adipocytes. Whether these DHT-induced effects also occur in human adipose tissue remains an area for future study. [*]There is very limited data available regarding DHT and effects on cognition. Further research is needed, particularly in light of animal data where DHT positively modified synaptic structure and significantly delayed cognitive impairment in a well-regarded animal model for Alzheimer’s disease. [*]Recent data indicating that higher levels of DHT were inversely associated with insulin resistance and risk of diabetes merit further mechanistic investigation to understand whether this action is separate from that of T. [/LIST] There was a study showing extremely elevated DHT levels (around 500+ ng/dL) for I think 24 months without negative side effects (along the specific markers and metrics they were keeping track of of course). However in that study Testosterone wasn't supplemented and therefore Test levels fell and were severely depressed throughout the study, so those findings don't necessarily represent what hyper-elevated DHT levels would do to someone on TRT long term. In general negative side effects as a function of hormone levels follow a classic "u" curve, whereby too low or too high levels lead to dose-dependent increased negative sides. Just because there isn't research showing those negative side effects doesn't mean they won't happen. At some point, in the absence of specific enough research I think common sense should prevail and to me, that means running DHT at 5-10x the range for a few decades is probably a bad idea [/QUOTE]
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