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<blockquote data-quote="madman" data-source="post: 211148" data-attributes="member: 13851"><p>When using the lower strength (1%) big pharma transdermal gels most men will need the higher end dose of 100 mg T/day (10 g of gel) to achieve high-end or in some cases very high T levels.</p><p></p><p>Seeing as you have been using transdermal T for 2 years and most likely feel good overall then if cost is the issue I would look into a compounded transdermal T cream before jumping on injections.</p><p></p><p>You need to keep in mind that although many may tend to prefer injections over transdermal the main benefit of a transdermal application is that it provides intraday T level variations similar to normal circadian secretion.</p><p></p><p><em><strong><strong>*The daily dosing frequency of the topical gel products results in a PK profile with a resemblance to that of endogenous T in younger males</strong></strong></em></p><p></p><p>Many end up using compounded transdermal T creams as the strength is much higher 5-20%.</p><p></p><p>Much less needs to be applied let alone the overall cost of the medication is much cheaper.</p><p></p><p>Most are using 20% strength (200mg/mL) and unfortunately many end up on that 200 mg T twice daily application protocol which would surely result in absurdly high TT/FT levels let alone steady-state.</p><p></p><p>Many can easily achieve healthy let alone very high T levels on much less especially when applied strictly scrotal.</p><p></p><p>Some men prefer a once-daily application protocol.</p><p></p><p>If anything seeing as the cost may be the issue then I would at least look into using a compounded transdermal T cream before switching over to injections.</p><p></p><p>Comes down to the individual as some men prefer/feel great using transdermal T whereas many others prefer injections.</p><p></p><p>A large percentage of men are using intramuscular/subcutaneous injections using various injection protocols (once weekly, twice weekly, M/W/F, EOD, daily) and in no way are mimicking the natural 24hr circadian rhythm of a healthy young male.</p><p></p><p>Steady-state, many are running levels well into the supra-physiological range 24/7.</p><p></p><p>Top it off with the fact that when using exogenous T <u>many are forcing levels upon themselves that the body would never produce naturally</u>.</p><p></p><p>The closest you could get to mimicking the natural 24hr circadian rhythm would be using the T patch or transdermal T.</p><p></p><p>Natural endogenous testosterone secretion is pulsatile and diurnal.</p><p></p><p><em><strong><strong>*All IM TTh preparations result in PK profiles that are unlike those of the normal diurnal variation of healthy young or older men</strong></strong></em></p><p></p><p>You need to keep in mind that you may be in for a bumpy ride when changing a protocol (method of T, dose, injection frequency).</p><p></p><p></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/pk-of-tth-and-diurnal-variation-of-testosterone.24117/[/URL]</p><p></p><p></p><p><strong>4. <u>Diurnal Variation in Serum T Levels</u></strong></p><p><strong></strong></p><p><strong><em>Diurnal variation in endogenous serum T levels in healthy men is well documented, with the highest T levels in the morning and lowest values in the afternoon and early evening, although the amplitudes of peak and trough levels vary by age.</em></strong><em> In 1983, a study by Bremner et al showed that there was a clear difference between serum T levels in normal young men (mean age 25.2 years) and older men (mean age 71.0 years).5 <strong>In young men, serum T levels were highest in the morning, falling to their lowest levels approximately 12 hours later and gradually increasing again to peak levels the next morning. Furthermore, a study to determine how endogenous T levels vary over clinic hours revealed that in 30- to 40-year-old men, morning total T levels are 30% to 35% higher than levels measured in the mid to late afternoon. This amplitude in daily endogenous T variation decreases with age, with a morning-to-afternoon difference of only 10% in 70-year-old men.90</strong> The morning-to-afternoon total T ratios in young and older men were approximately 1.3 and 1.1, respectively, similar to what was observed in the Bremner study. These observations have led to recommendations in various clinical guidelines, including those of the American Urology Association in 2018, to obtain early morning blood tests for the diagnosis of TD, a threshold defined as <10.4 nmol/L (300 ng/dL). 3 <strong>While endogenous serum T exhibits a clear diurnal pattern in young men that appears to be blunted naturally as men age, there does not appear to be much diurnal variation for DHT, SHBG, LH, FSH, or E2, regardless of age.90</strong></em></p><p></p><p><strong><em>Diurnal variation appears to be absent in men with TD.</em></strong><em> Using a population mixed-effect analysis, Gupta et al showed that no circadian rhythm was detected in men with TD, and the mean endogenous T levels in men with TD (serum T levels <10.4 nmol/L, or 300 ng/dL) were much lower than in healthy young (mean age, 28 years) or older (mean age, 71 years) men. 91 Consistent with the literature, their modeling of circadian T in healthy young and older men revealed peak-to-trough ratios of 1.3 and 1.2, respectively. Additionally, univariate analysis of cross-sectional data from 3,007 older men (≥40 years) showed that the proportion of men with serum T levels <10.4 nmol/L (300 ng/dL) did not significantly change during the day (P<0.11), further supporting that endogenous T diurnal variation is absent in men with TD.92 Results from a study by Shlykova et al evaluating endogenous T levels over a 24-hour period in 21 healthy male volunteers showed that men with baseline serum T levels <10.4 nmol/L (300 ng/dL) did not demonstrate diurnal variation within the 24-hour sampling period. 93 To understand the circadian rhythmicity of T levels in men with TD, a population kinetic model built by Gonzales-Sales et al, using baseline T profiles from 859 men with TD, predicted a base T value of 8.3 nmol/L (239 ng/dL), with the amplitude of oscillation estimated to be 1.1 nmol/L (32.4 ng/dL). 94 <strong>Their model also predicted that a stretched cosine function was more suitable to describe the circadian behavior of T levels of men with TD, as trough levels occurred approximately 5 hours after peak T levels, and levels then increased until the next peak occurred approximately 19 hours later.94</strong></em></p><p><em></em></p><p><em>A variety of exogenous TTh are available to increase serum T to physiologic levels in males with TD and may alleviate symptoms associated with TD.2<strong> Some T replacement options more closely mimic the circadian levels of T identified in older men, whereas other options seem to provide PK profiles closer to those of younger men (Fig. 1 [Please put figure as close as possible to this callout] and Table 1). <strong>Some TTh options provide profiles that exceed the frequency of the natural T circadian rhythmicity.</strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong>*</strong></strong>Once-weekly SC TE injections bring mean T levels into the physiologic range within 24 hours after the first dose, with a total T Cmax/Cmin ratio of 1.8.<strong><strong> The PK profile appears to mimic the flatter profile of older males’ endogenous T.95 </strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong>*IM T injections can cause both supratherapeutic T levels post-injection and subtherapeutic levels during the dosing interval, and depending on the formulation and dosage,</strong></strong> peak-to-trough ratios of IM TC and TE range between 2 and 5.3. </em></p><p><em></em></p><p><em><strong><strong>*Longer-lasting TU injections do not demonstrate the supratherapeutic peaks of other IM formulations, </strong></strong>with trough levels occurring at later time points after each injection and a peak-to-trough ratio of approximately 2.6 to 2.8. </em></p><p><em></em></p><p><em><strong><strong>*All IM TTh preparations result in PK profiles that are unlike those of the normal diurnal variation of healthy young or older men</strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong>*</strong></strong>Daily transdermal gels and solutions, and nasal and oral T products, provide a consistent serum T level within the physiologic range in most patients. <strong><strong>The daily dosing frequency of the topical gel products results in a PK profile with a resemblance to that of endogenous T in younger males</strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong>*</strong></strong>Men using nasal and oral T products are able to achieve mean serum T levels that are within the normal range<strong><strong>, </strong></strong>but they experience several T peaks and troughs throughout the day because of the multiple daily dosing regimens required (2 or 3 times/day).<strong><strong> This results in a PK profile that significantly deviates from the endogenous PK profiles of both younger and older patients</strong></strong></em></p><p><em><strong><strong></strong></strong></em></p><p><em><strong><strong>*No single formulation appears to provide an exposure profile that would resemble diurnal variation of both young and older men</strong></strong></em></p></blockquote><p></p>
[QUOTE="madman, post: 211148, member: 13851"] When using the lower strength (1%) big pharma transdermal gels most men will need the higher end dose of 100 mg T/day (10 g of gel) to achieve high-end or in some cases very high T levels. Seeing as you have been using transdermal T for 2 years and most likely feel good overall then if cost is the issue I would look into a compounded transdermal T cream before jumping on injections. You need to keep in mind that although many may tend to prefer injections over transdermal the main benefit of a transdermal application is that it provides intraday T level variations similar to normal circadian secretion. [I][B][B]*The daily dosing frequency of the topical gel products results in a PK profile with a resemblance to that of endogenous T in younger males[/B][/B][/I] Many end up using compounded transdermal T creams as the strength is much higher 5-20%. Much less needs to be applied let alone the overall cost of the medication is much cheaper. Most are using 20% strength (200mg/mL) and unfortunately many end up on that 200 mg T twice daily application protocol which would surely result in absurdly high TT/FT levels let alone steady-state. Many can easily achieve healthy let alone very high T levels on much less especially when applied strictly scrotal. Some men prefer a once-daily application protocol. If anything seeing as the cost may be the issue then I would at least look into using a compounded transdermal T cream before switching over to injections. Comes down to the individual as some men prefer/feel great using transdermal T whereas many others prefer injections. A large percentage of men are using intramuscular/subcutaneous injections using various injection protocols (once weekly, twice weekly, M/W/F, EOD, daily) and in no way are mimicking the natural 24hr circadian rhythm of a healthy young male. Steady-state, many are running levels well into the supra-physiological range 24/7. Top it off with the fact that when using exogenous T [U]many are forcing levels upon themselves that the body would never produce naturally[/U]. The closest you could get to mimicking the natural 24hr circadian rhythm would be using the T patch or transdermal T. Natural endogenous testosterone secretion is pulsatile and diurnal. [I][B][B]*All IM TTh preparations result in PK profiles that are unlike those of the normal diurnal variation of healthy young or older men[/B][/B][/I] You need to keep in mind that you may be in for a bumpy ride when changing a protocol (method of T, dose, injection frequency). [URL unfurl="true"]https://www.excelmale.com/forum/threads/pk-of-tth-and-diurnal-variation-of-testosterone.24117/[/URL] [B]4. [U]Diurnal Variation in Serum T Levels[/U] [I]Diurnal variation in endogenous serum T levels in healthy men is well documented, with the highest T levels in the morning and lowest values in the afternoon and early evening, although the amplitudes of peak and trough levels vary by age.[/I][/B][I] In 1983, a study by Bremner et al showed that there was a clear difference between serum T levels in normal young men (mean age 25.2 years) and older men (mean age 71.0 years).5 [B]In young men, serum T levels were highest in the morning, falling to their lowest levels approximately 12 hours later and gradually increasing again to peak levels the next morning. Furthermore, a study to determine how endogenous T levels vary over clinic hours revealed that in 30- to 40-year-old men, morning total T levels are 30% to 35% higher than levels measured in the mid to late afternoon. This amplitude in daily endogenous T variation decreases with age, with a morning-to-afternoon difference of only 10% in 70-year-old men.90[/B] The morning-to-afternoon total T ratios in young and older men were approximately 1.3 and 1.1, respectively, similar to what was observed in the Bremner study. These observations have led to recommendations in various clinical guidelines, including those of the American Urology Association in 2018, to obtain early morning blood tests for the diagnosis of TD, a threshold defined as <10.4 nmol/L (300 ng/dL). 3 [B]While endogenous serum T exhibits a clear diurnal pattern in young men that appears to be blunted naturally as men age, there does not appear to be much diurnal variation for DHT, SHBG, LH, FSH, or E2, regardless of age.90[/B][/I] [B][I]Diurnal variation appears to be absent in men with TD.[/I][/B][I] Using a population mixed-effect analysis, Gupta et al showed that no circadian rhythm was detected in men with TD, and the mean endogenous T levels in men with TD (serum T levels <10.4 nmol/L, or 300 ng/dL) were much lower than in healthy young (mean age, 28 years) or older (mean age, 71 years) men. 91 Consistent with the literature, their modeling of circadian T in healthy young and older men revealed peak-to-trough ratios of 1.3 and 1.2, respectively. Additionally, univariate analysis of cross-sectional data from 3,007 older men (≥40 years) showed that the proportion of men with serum T levels <10.4 nmol/L (300 ng/dL) did not significantly change during the day (P<0.11), further supporting that endogenous T diurnal variation is absent in men with TD.92 Results from a study by Shlykova et al evaluating endogenous T levels over a 24-hour period in 21 healthy male volunteers showed that men with baseline serum T levels <10.4 nmol/L (300 ng/dL) did not demonstrate diurnal variation within the 24-hour sampling period. 93 To understand the circadian rhythmicity of T levels in men with TD, a population kinetic model built by Gonzales-Sales et al, using baseline T profiles from 859 men with TD, predicted a base T value of 8.3 nmol/L (239 ng/dL), with the amplitude of oscillation estimated to be 1.1 nmol/L (32.4 ng/dL). 94 [B]Their model also predicted that a stretched cosine function was more suitable to describe the circadian behavior of T levels of men with TD, as trough levels occurred approximately 5 hours after peak T levels, and levels then increased until the next peak occurred approximately 19 hours later.94[/B] A variety of exogenous TTh are available to increase serum T to physiologic levels in males with TD and may alleviate symptoms associated with TD.2[B] Some T replacement options more closely mimic the circadian levels of T identified in older men, whereas other options seem to provide PK profiles closer to those of younger men (Fig. 1 [Please put figure as close as possible to this callout] and Table 1). [B]Some TTh options provide profiles that exceed the frequency of the natural T circadian rhythmicity. *[/B][/B]Once-weekly SC TE injections bring mean T levels into the physiologic range within 24 hours after the first dose, with a total T Cmax/Cmin ratio of 1.8.[B][B] The PK profile appears to mimic the flatter profile of older males’ endogenous T.95 *IM T injections can cause both supratherapeutic T levels post-injection and subtherapeutic levels during the dosing interval, and depending on the formulation and dosage,[/B][/B] peak-to-trough ratios of IM TC and TE range between 2 and 5.3. [B][B]*Longer-lasting TU injections do not demonstrate the supratherapeutic peaks of other IM formulations, [/B][/B]with trough levels occurring at later time points after each injection and a peak-to-trough ratio of approximately 2.6 to 2.8. [B][B]*All IM TTh preparations result in PK profiles that are unlike those of the normal diurnal variation of healthy young or older men *[/B][/B]Daily transdermal gels and solutions, and nasal and oral T products, provide a consistent serum T level within the physiologic range in most patients. [B][B]The daily dosing frequency of the topical gel products results in a PK profile with a resemblance to that of endogenous T in younger males *[/B][/B]Men using nasal and oral T products are able to achieve mean serum T levels that are within the normal range[B][B], [/B][/B]but they experience several T peaks and troughs throughout the day because of the multiple daily dosing regimens required (2 or 3 times/day).[B][B] This results in a PK profile that significantly deviates from the endogenous PK profiles of both younger and older patients *No single formulation appears to provide an exposure profile that would resemble diurnal variation of both young and older men[/B][/B][/I] [/QUOTE]
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