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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Side Effect Management
Clinical Use of Aromatase Inhibitors in Adult Males
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<blockquote data-quote="madman" data-source="post: 131951" data-attributes="member: 13851"><p>Every time in every post you always speak of one experiencing a crash as if e2 is non existent!</p><p></p><p></p><p></p><p></p><p><strong>Brief Introduction to the AIs</strong></p><p></p><p></p><p>The enzyme aromatase is found in the endoplasmic reticulum of the estrogen-producing cell and is the key enzyme in estrogen biosynthesis. The enzyme aromatase is able to convert testosterone into estradiol and androstenedione into estrone. Aromatase activity has been demonstrated in <strong><span style="color: rgb(184, 49, 47)">gonads, placenta, brain[33], adipose tissue[34,35], muscle [36], hair [37], bone [38], and vascular tissue [39]</span></strong>.</p><p></p><p></p><p>AIs are classified as either <strong><span style="color: rgb(184, 49, 47)">type 1 (steroidal) or type2 (nonsteroidal).</span></strong> Examples of steroidal AIs are testolactone, formestane, and exemestane, which inhibit aromatase activity by mimicking the substrate androstenedione. <strong><span style="color: rgb(184, 49, 47)">They irreversibly inhibit the aromatase enzyme by covalently binding to it; as such they are also known as “suicidal inhibitors.”</span></strong></p><p></p><p>Nonsteroidal AIs <strong><span style="color: rgb(184, 49, 47)">inhibit enzyme activity by reversibly binding with the heme iron of the enzyme, resulting in competitive inhibition</span></strong>. Examples of nonsteroidal AIs are aminoglutethimide, fadrozole, anastrozol, letrozole, and vorozole (Table 1). </p><p></p><p></p><p>AIs are further classified into generations based on their efficacy. <strong><span style="color: rgb(184, 49, 47)">First generation inhibitors (e.g., aminoglutethimide) are relatively weak and nonspecific, whereas third generation AIs (e.g., letrozole and anastrozole) are most potent, most specific, and least toxic.</span></strong> Their pharmacokinetic properties (t1/2 of 48 hours for ansatrozole and letrozole and t1/2 of 27 hours for exemestane) allow for a once-daily dosing schedule. Their selective inhibitory properties negate the need for corticosteroidal or mineralocorticoid supplementation, which is essential for the nonspecific AI aminogluthimide.<strong><span style="color: rgb(184, 49, 47)"> The second generation AIs are in between with regard to potency, specificity, and toxicity (e.g., formestane and fadrozole). </span></strong><span style="color: rgb(0, 0, 0)"><strong>Third generation AIs have been reported to have close to </strong></span><span style="color: rgb(184, 49, 47)"><strong>100%</strong></span> <span style="color: rgb(0, 0, 0)"><strong>inhibition of the enzyme</strong>, <strong>but this is not the case in males</strong>.</span> <strong>In men, third-generation AIs will decrease the mean plasma estradiol/testosterone ratio by <span style="color: rgb(184, 49, 47)">77% </span></strong>[41,42].This can be explained by the higher plasma concentration of testosterone in eugonal adult men compared with women.<strong><span style="color: rgb(26, 188, 156)"> .</span><span style="color: rgb(41, 105, 176)">Because inhibition of aromatase is dose dependent, aromatase is less suppressed in the testis compared with adipose and muscle, thus explaining the incomplete efficacy of aromatase inhibition in males.</span></strong> <strong><span style="color: rgb(41, 105, 176)">The molar ratio of testosterone to AI and testicular aromatase activity is higher compared with adipose and muscle tissue.</span></strong> As mentioned earlier in this article, low estradiol levels are detrimental to bone health and sexual function. Thus, this incomplete suppression may be advantageous to men,and this lowers the risk of the potential side effects of AIs. <strong>Long-term use of potent AIs reduces circulating estradiol levels by <span style="color: rgb(184, 49, 47)">88%</span></strong> [43]. This is associated with adverse effects on bone [44,45] and could possibly be associated with increased body fat in men [22].</p></blockquote><p></p>
[QUOTE="madman, post: 131951, member: 13851"] Every time in every post you always speak of one experiencing a crash as if e2 is non existent! [B]Brief Introduction to the AIs[/B] The enzyme aromatase is found in the endoplasmic reticulum of the estrogen-producing cell and is the key enzyme in estrogen biosynthesis. The enzyme aromatase is able to convert testosterone into estradiol and androstenedione into estrone. Aromatase activity has been demonstrated in [B][COLOR=rgb(184, 49, 47)]gonads, placenta, brain[33], adipose tissue[34,35], muscle [36], hair [37], bone [38], and vascular tissue [39][/COLOR][/B]. AIs are classified as either [B][COLOR=rgb(184, 49, 47)]type 1 (steroidal) or type2 (nonsteroidal).[/COLOR][/B] Examples of steroidal AIs are testolactone, formestane, and exemestane, which inhibit aromatase activity by mimicking the substrate androstenedione. [B][COLOR=rgb(184, 49, 47)]They irreversibly inhibit the aromatase enzyme by covalently binding to it; as such they are also known as “suicidal inhibitors.”[/COLOR][/B] Nonsteroidal AIs [B][COLOR=rgb(184, 49, 47)]inhibit enzyme activity by reversibly binding with the heme iron of the enzyme, resulting in competitive inhibition[/COLOR][/B]. Examples of nonsteroidal AIs are aminoglutethimide, fadrozole, anastrozol, letrozole, and vorozole (Table 1). AIs are further classified into generations based on their efficacy. [B][COLOR=rgb(184, 49, 47)]First generation inhibitors (e.g., aminoglutethimide) are relatively weak and nonspecific, whereas third generation AIs (e.g., letrozole and anastrozole) are most potent, most specific, and least toxic.[/COLOR][/B] Their pharmacokinetic properties (t1/2 of 48 hours for ansatrozole and letrozole and t1/2 of 27 hours for exemestane) allow for a once-daily dosing schedule. Their selective inhibitory properties negate the need for corticosteroidal or mineralocorticoid supplementation, which is essential for the nonspecific AI aminogluthimide.[B][COLOR=rgb(184, 49, 47)] The second generation AIs are in between with regard to potency, specificity, and toxicity (e.g., formestane and fadrozole). [/COLOR][/B][COLOR=rgb(0, 0, 0)][B]Third generation AIs have been reported to have close to [/B][/COLOR][COLOR=rgb(184, 49, 47)][B]100%[/B][/COLOR][B][COLOR=rgb(184, 49, 47)] [/COLOR][/B][COLOR=rgb(0, 0, 0)][B]inhibition of the enzyme[/B], [B]but this is not the case in males[/B].[/COLOR] [B]In men, third-generation AIs will decrease the mean plasma estradiol/testosterone ratio by [COLOR=rgb(184, 49, 47)]77% [/COLOR][/B][41,42].This can be explained by the higher plasma concentration of testosterone in eugonal adult men compared with women.[B][COLOR=rgb(26, 188, 156)] .[/COLOR][COLOR=rgb(41, 105, 176)]Because inhibition of aromatase is dose dependent, aromatase is less suppressed in the testis compared with adipose and muscle, thus explaining the incomplete efficacy of aromatase inhibition in males.[/COLOR][/B][COLOR=rgb(41, 105, 176)][B] [/B][/COLOR][B][COLOR=rgb(41, 105, 176)]The molar ratio of testosterone to AI and testicular aromatase activity is higher compared with adipose and muscle tissue.[/COLOR][/B] As mentioned earlier in this article, low estradiol levels are detrimental to bone health and sexual function. Thus, this incomplete suppression may be advantageous to men,and this lowers the risk of the potential side effects of AIs. [B]Long-term use of potent AIs reduces circulating estradiol levels by [COLOR=rgb(184, 49, 47)]88%[/COLOR][/B] [43]. This is associated with adverse effects on bone [44,45] and could possibly be associated with increased body fat in men [22]. [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Side Effect Management
Clinical Use of Aromatase Inhibitors in Adult Males
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