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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
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<blockquote data-quote="tareload" data-source="post: 222597"><p>Rodent Free #cuttheshit for [USER=18514]@DS3[/USER]</p><p></p><p>[USER=13851]@madman[/USER]</p><p>[USER=3]@Nelson Vergel[/USER]</p><p></p><p>Interesting study in natal human females that are TGM:</p><p></p><p>[URL unfurl="true"]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/[/URL]</p><p></p><p>[ATTACH=full]21464[/ATTACH]</p><p></p><p></p><p>[ATTACH=full]21465[/ATTACH]</p><p>[ATTACH=full]21466[/ATTACH]</p><p></p><p></p><h2><em><span style="font-family: 'Georgia'"><em>DISCUSSION</em></span></em></h2><p><em><span style="font-family: 'Georgia'">We demonstrated for the first time that physiological testosterone administration during HT was associated with impaired endothelial function in young TGM compared to CGF women. Our findings are consistent with earlier data showing endothelium mediated vasodilation is attenuated in lean, insulin-sensitive women with AE-PCOS with endogenous hyperandrogenism<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R11" target="_blank">11</a>. Importantly, the difference in endothelial function between TGM and CGF was found despite comparable levels of traditional cardiovascular risk factors including BMI, lipid levels and blood pressure, suggesting that other mechanisms such as inflammation or the direct effect of androgens may contribute to changes in endothelial function. There was a small but statistically significant difference in HbA1C in the TGM (5.0 vs 4.7%, P=0.048), however the levels were well within the normal range and unlikely to have clinically relevant impact on vascular function. However, we cannot entirely exclude the possibility that subtle changes in cardiometabolic measurements may have a deleterious effect on endothelial function with long-term treatment. Earlier studies have shown adverse effects of testosterone on lipid levels and blood pressure<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R17" target="_blank">17</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R24" target="_blank">24</a>, raising concern for increased cardiovascular risk with chronic testosterone exposure. Therefore, attention to cardiometabolic risk factors should be integral to the care of TGM. Finally, because of experimental constraints, our laboratory tests were performed by different laboratories so we were unable to directly compare lipids and hormones between the two groups so these studies should be repeated with blood analysis performed using the same assays for both groups.</span></em></p><p><em><span style="font-family: 'Georgia'"></span></em></p><p><em><span style="font-family: 'Georgia'">Endothelial dysfunction constitutes “the early pivotal event in atherosclerosis”<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R25" target="_blank">25</a>, because it precedes clinically detectable atherosclerotic plaques in the coronary arteries. Healthy endothelial function may be described as a balance of endothelial vasoconstrictor/vasodilator factors. A primary feature of normally functioning endothelium is the production of nitric oxide in response a number of different agonists (e.g. shear stress in FMD). Testosterone exposure is also associated with impaired agonist-triggered endothelial NO release in women<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R3" target="_blank">3</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R4" target="_blank">4</a>, and is therefore a major driver of endothelial dysfunction. Activation of the AR in women may result in impaired, agonist-triggered endothelial NO release and/or NO responsiveness. A recent study in our laboratory demonstrated impaired endothelin-1 (agonist) triggered vasodilation in lean, insulin sensitive women with AE-PCOS, indicating an independent effect of androgen on vascular pathology in these women with high testosterone exposure but no insulin resistance or obesity<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R11" target="_blank">11</a>. This same study indicated the endothelial dysfunction in AE-PCOS is mediated through an androgen effect on the NO pathway<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R11" target="_blank">11</a>. Earlier data in PCOS had demonstrated that inflammation and inflammatory factors including cytokines, oxidative stress and NF-κB activation<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R26" target="_blank">26</a> also contribute to the impaired NO release or responsiveness<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R5" target="_blank">5</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R6" target="_blank">6</a>. These data are consistent with our current findings that the impaired endothelial function in TGM is independent of obesity or blood lipids and likely associated with inflammatory factors associated with the testosterone exposure.</span></em></p><p></p><p><strong><em><span style="font-family: 'Georgia'"><strong>Testosterone is an acute vasodilator and in men may protect against endothelial dysfunction<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R27" target="_blank">27</a>. Androgen receptors are expressed in cells throughout the cardiovascular system, including endothelial cells<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R28" target="_blank">28</a> and vascular smooth muscle cells (VSMCs)<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R29" target="_blank">29</a>, although the impact of testosterone administration on the cardiovascular system in men is varied<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R2" target="_blank">2</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R30" target="_blank">30</a>–<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R33" target="_blank">33</a>. In contrast, androgens may induce detrimental outcomes on the cardiovascular system in women<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R2" target="_blank">2</a>–<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R4" target="_blank">4</a>. In general, the engagement of androgen and the androgen receptor results in impaired, agonist-triggered endothelial NO release in women, a likely cause of the sex differences in testosterone effects on endothelial function. A recent meta-analysis of androgen (DHT) treatment showed dyslipidemia at 3, 6 and 24 months of testosterone treatment in transmen<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R17" target="_blank">17</a>. While HT with testosterone also induced blood pressure increases, insulin resistance, and dyslipidemia<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R17" target="_blank">17</a>, cardiovascular morbidity or mortality was not yet apparent in these young transgender men<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R24" target="_blank">24</a>. No studies have yet followed transgender men into the aging process as cardiovascular disease risks accelerate, therefore the long-term impact on cardiovascular disease remains unknown.</strong></span></em></strong></p><p><strong><em><span style="font-family: 'Georgia'"><strong></strong></span></em></strong></p><p><strong><em><span style="font-family: 'Georgia'"><strong>Earlier studies have shown Hb and Hct during testosterone treatment (in men) can increase iron and red blood cell formation<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R34" target="_blank">34</a>, and that Hb is inversely related to forearm endothelial-dependent vasodilation<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R35" target="_blank">35</a>. However, in this study, while Hct was greater in the TGM versus the CGF, there was no relationship within either group to FMD or when we considered the groups as a whole. Further studies examining this specific relationship are required as our blood samples and FMD measures in TGM were not taken on the same day, and Hb and Hct are sensitive to hydration and posture, among other variables.</strong></span></em></strong></p><p></p><p><em><span style="font-family: 'Georgia'">In women, [TTotal]S is associated with greater risk of diabetes and related cardiovascular comorbidities<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R37" target="_blank">37</a>. In the present study, we noted small but significantly greater HbA1C in the TGM (5.0 vs 4.7, <em>P</em>=0.048) in this young, healthy cohort. In this group we would expect the incidence of impaired glucose metabolism to be very low. The normal range for HbA1C is <5.7%, prediabetes is defined as an HbA1C 5.7–6.4%, and diabetes is defined as an HbA1C ≥ 6.5%. All subjects in both groups were in the normal range (4.0–5.6%), suggesting while this was statically different, there is little physiological or clinical consequence.</span></em></p><p></p><h3><em><span style="font-family: 'Georgia'">Conclusions</span></em></h3><p><em><span style="font-family: 'Georgia'">Ours is the first study to examine the androgen effects on endothelial function in TGM. We demonstrated that the hyperandrogenic milieu in TGM is a primary factor associated with endothelial dysfunction, independent of lipids, blood pressure and BMI. Our present study supports earlier studies from our laboratory demonstrating that poor NO responsiveness is a key causative link in natal females exposed to chronic endogenous and/or high levels of exogenous androgens leading to endothelial dysfunction and ultimately cardiovascular disease. Future studies should address how changes in other hormones such as estrogen, or other substances, such as inflammatory cytokines, may impact changes in vascular function during HT. As described earlier, endothelial dysfunction in these TGM occurred independent of differences in lipids, BMI or blood pressure indicating a separate etiology. Understanding the mechanisms by which exogenous androgens mediate endothelial dysfunction in TGM may allow for early interventions to mitigate the potential long-term cardiovascular risk.</span></em></p><p></p><p></p><p><span style="font-family: 'Verdana'">As pointed out in the Hct thread, there's obviously a limit for each individual how much TT they can handle before FMD/endothelial function becomes impaired rather than enhanced (important in the context of Hct elevation, blood viscosity, shear stress). Hence, u-shaped curve for TT on morbiditiy just like most other hormones, co-factors, etc.</span></p></blockquote><p></p>
[QUOTE="tareload, post: 222597"] Rodent Free #cuttheshit for [USER=18514]@DS3[/USER] [USER=13851]@madman[/USER] [USER=3]@Nelson Vergel[/USER] Interesting study in natal human females that are TGM: [URL unfurl="true"]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/[/URL] [ATTACH type="full" alt="1651167302838.png"]21464[/ATTACH] [ATTACH type="full" alt="1651167336739.png"]21465[/ATTACH] [ATTACH type="full" alt="1651167360395.png"]21466[/ATTACH] [HEADING=1][I][FONT=Georgia][I]DISCUSSION[/I][/FONT][/I][/HEADING] [I][FONT=Georgia]We demonstrated for the first time that physiological testosterone administration during HT was associated with impaired endothelial function in young TGM compared to CGF women. Our findings are consistent with earlier data showing endothelium mediated vasodilation is attenuated in lean, insulin-sensitive women with AE-PCOS with endogenous hyperandrogenism[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R11']11[/URL]. Importantly, the difference in endothelial function between TGM and CGF was found despite comparable levels of traditional cardiovascular risk factors including BMI, lipid levels and blood pressure, suggesting that other mechanisms such as inflammation or the direct effect of androgens may contribute to changes in endothelial function. There was a small but statistically significant difference in HbA1C in the TGM (5.0 vs 4.7%, P=0.048), however the levels were well within the normal range and unlikely to have clinically relevant impact on vascular function. However, we cannot entirely exclude the possibility that subtle changes in cardiometabolic measurements may have a deleterious effect on endothelial function with long-term treatment. Earlier studies have shown adverse effects of testosterone on lipid levels and blood pressure[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R17']17[/URL], [URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R24']24[/URL], raising concern for increased cardiovascular risk with chronic testosterone exposure. Therefore, attention to cardiometabolic risk factors should be integral to the care of TGM. Finally, because of experimental constraints, our laboratory tests were performed by different laboratories so we were unable to directly compare lipids and hormones between the two groups so these studies should be repeated with blood analysis performed using the same assays for both groups. Endothelial dysfunction constitutes “the early pivotal event in atherosclerosis”[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R25']25[/URL], because it precedes clinically detectable atherosclerotic plaques in the coronary arteries. Healthy endothelial function may be described as a balance of endothelial vasoconstrictor/vasodilator factors. A primary feature of normally functioning endothelium is the production of nitric oxide in response a number of different agonists (e.g. shear stress in FMD). Testosterone exposure is also associated with impaired agonist-triggered endothelial NO release in women[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R3']3[/URL], [URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R4']4[/URL], and is therefore a major driver of endothelial dysfunction. Activation of the AR in women may result in impaired, agonist-triggered endothelial NO release and/or NO responsiveness. A recent study in our laboratory demonstrated impaired endothelin-1 (agonist) triggered vasodilation in lean, insulin sensitive women with AE-PCOS, indicating an independent effect of androgen on vascular pathology in these women with high testosterone exposure but no insulin resistance or obesity[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R11']11[/URL]. This same study indicated the endothelial dysfunction in AE-PCOS is mediated through an androgen effect on the NO pathway[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R11']11[/URL]. Earlier data in PCOS had demonstrated that inflammation and inflammatory factors including cytokines, oxidative stress and NF-κB activation[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R26']26[/URL] also contribute to the impaired NO release or responsiveness[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R5']5[/URL], [URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R6']6[/URL]. These data are consistent with our current findings that the impaired endothelial function in TGM is independent of obesity or blood lipids and likely associated with inflammatory factors associated with the testosterone exposure.[/FONT][/I] [B][I][FONT=Georgia][B]Testosterone is an acute vasodilator and in men may protect against endothelial dysfunction[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R27']27[/URL]. Androgen receptors are expressed in cells throughout the cardiovascular system, including endothelial cells[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R28']28[/URL] and vascular smooth muscle cells (VSMCs)[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R29']29[/URL], although the impact of testosterone administration on the cardiovascular system in men is varied[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R2']2[/URL], [URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R30']30[/URL]–[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R33']33[/URL]. In contrast, androgens may induce detrimental outcomes on the cardiovascular system in women[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R2']2[/URL]–[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R4']4[/URL]. In general, the engagement of androgen and the androgen receptor results in impaired, agonist-triggered endothelial NO release in women, a likely cause of the sex differences in testosterone effects on endothelial function. A recent meta-analysis of androgen (DHT) treatment showed dyslipidemia at 3, 6 and 24 months of testosterone treatment in transmen[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R17']17[/URL]. While HT with testosterone also induced blood pressure increases, insulin resistance, and dyslipidemia[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R17']17[/URL], cardiovascular morbidity or mortality was not yet apparent in these young transgender men[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R24']24[/URL]. No studies have yet followed transgender men into the aging process as cardiovascular disease risks accelerate, therefore the long-term impact on cardiovascular disease remains unknown. Earlier studies have shown Hb and Hct during testosterone treatment (in men) can increase iron and red blood cell formation[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R34']34[/URL], and that Hb is inversely related to forearm endothelial-dependent vasodilation[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R35']35[/URL]. However, in this study, while Hct was greater in the TGM versus the CGF, there was no relationship within either group to FMD or when we considered the groups as a whole. Further studies examining this specific relationship are required as our blood samples and FMD measures in TGM were not taken on the same day, and Hb and Hct are sensitive to hydration and posture, among other variables.[/B][/FONT][/I][/B] [I][FONT=Georgia]In women, [TTotal]S is associated with greater risk of diabetes and related cardiovascular comorbidities[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957681/#R37']37[/URL]. In the present study, we noted small but significantly greater HbA1C in the TGM (5.0 vs 4.7, [I]P[/I]=0.048) in this young, healthy cohort. In this group we would expect the incidence of impaired glucose metabolism to be very low. The normal range for HbA1C is <5.7%, prediabetes is defined as an HbA1C 5.7–6.4%, and diabetes is defined as an HbA1C ≥ 6.5%. All subjects in both groups were in the normal range (4.0–5.6%), suggesting while this was statically different, there is little physiological or clinical consequence.[/FONT][/I] [HEADING=2][I][FONT=Georgia]Conclusions[/FONT][/I][/HEADING] [I][FONT=Georgia]Ours is the first study to examine the androgen effects on endothelial function in TGM. We demonstrated that the hyperandrogenic milieu in TGM is a primary factor associated with endothelial dysfunction, independent of lipids, blood pressure and BMI. Our present study supports earlier studies from our laboratory demonstrating that poor NO responsiveness is a key causative link in natal females exposed to chronic endogenous and/or high levels of exogenous androgens leading to endothelial dysfunction and ultimately cardiovascular disease. Future studies should address how changes in other hormones such as estrogen, or other substances, such as inflammatory cytokines, may impact changes in vascular function during HT. As described earlier, endothelial dysfunction in these TGM occurred independent of differences in lipids, BMI or blood pressure indicating a separate etiology. Understanding the mechanisms by which exogenous androgens mediate endothelial dysfunction in TGM may allow for early interventions to mitigate the potential long-term cardiovascular risk.[/FONT][/I] [FONT=Verdana]As pointed out in the Hct thread, there's obviously a limit for each individual how much TT they can handle before FMD/endothelial function becomes impaired rather than enhanced (important in the context of Hct elevation, blood viscosity, shear stress). Hence, u-shaped curve for TT on morbiditiy just like most other hormones, co-factors, etc.[/FONT] [/QUOTE]
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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
Nandrolone for Mood | Feeling much Better..
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