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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
Microdosing Enanthate
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<blockquote data-quote="madman" data-source="post: 214921" data-attributes="member: 13851"><p><strong>A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years (2014)</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>Discussion</strong></p><p></p><p><em>Using data-driven modeling and analysis, we have derived a normative model of total testosterone throughout the lifespan.<strong> We have shown that in the average healthy male testosterone is low in pre-puberty, rises from age 11, and <u>peaks at age 19 at 15.4 (7.2– 31.1) nmol/L [mean (2.5–97.5 percentile)]</u>. Thereafter TT falls slightly to age 40 years to 13.0 (6.6–25.3) nmol/L.</strong> We find no evidence to support a progressive decline in testosterone in middle-aged and older men, sometimes termed the ‘andropause’, as TT does not fall significantly in the average man after the age of 40 years. Our analyses show that the 95% prediction limit increases from 18.7 nmol/L at age 40 years to 24.5 nmol/L at age 88 years. This increase in variation with increasing age demonstrates that reference ranges for TT that do not take chronological age into account are inappropriate for the assessment of an individual’s testosterone levels.</em></p><p><em></em></p><p><em></em></p><p><em></em></p><p><em></em></p><p><em>*Our model is derived from data from multiple sources of the measurement of TT in over 10,000 healthy males aged between 3 and 101 years. This is both a strength and weakness of the study. The strength is that modeling power is increased by the provision of large numbers of data points for a wide range of ages: it has been previously shown that models that include both prepubertal, pubertal, and adult ages can be used to derive important insights for a restricted age range [47]. <strong>The weakness is the approximate heterogeneity of the values obtained from diverse sources, especially as assay conversion factors were used that have known high correlation but are nevertheless inexact. This includes studies that involve convenience samples (e.g. primary care and outpatient attendees) as well as those that involve population-derived cohorts. Further limitations of our approach are that insufficient data were found to model accurately neonatal ages and that we had to exclude potentially useful studies that used in-house assays which lack standardization and harmonization, and for which no conversion formula has been published [48].</strong> <strong>Ten of the thirteen studies used as data sources (Table 1) excluded subjects taking medication that could affect the endocrine system, but three studies [5,6,49] (combined n = 2,371 of 10,097) do not have equivalently explicit inclusion criteria. <u>We can therefore not rule out the possibility that a small number of subjects were on medication that increased their TT levels</u>.</strong></em></p><p></p><p></p><p></p><p></p><p><strong>Figure 4. The validated model. Our dataset (n = 10,098) of observed total testosterone for ages 3–88 years, split into normative ranges determined by mean predicted values (blue line) and one (red), two (blue), three (green), and four (purple) standard deviations higher and lower than the predicted values. doi:10.1371/journal.pone.0109346.g004</strong></p><p><strong>[ATTACH=full]19021[/ATTACH]</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>Figure 5. The validated model in centiles. Normative ranges for the model of total testosterone from ages 3–88 years. In the average case (red line) total testosterone remains constant for age .40. However, the variance in normative ranges increases for these ages, with 1st to 99th centile ranges of 5.6–27.6 nmol/L at age 35 years and 4.1–33.1 nmol/L at age 88 years. doi:10.1371/journal.pone.0109346.g005</strong></p><p><strong>[ATTACH=full]19022[/ATTACH]</strong></p></blockquote><p></p>
[QUOTE="madman, post: 214921, member: 13851"] [B]A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years (2014) Discussion[/B] [I]Using data-driven modeling and analysis, we have derived a normative model of total testosterone throughout the lifespan.[B] We have shown that in the average healthy male testosterone is low in pre-puberty, rises from age 11, and [U]peaks at age 19 at 15.4 (7.2– 31.1) nmol/L [mean (2.5–97.5 percentile)][/U]. Thereafter TT falls slightly to age 40 years to 13.0 (6.6–25.3) nmol/L.[/B] We find no evidence to support a progressive decline in testosterone in middle-aged and older men, sometimes termed the ‘andropause’, as TT does not fall significantly in the average man after the age of 40 years. Our analyses show that the 95% prediction limit increases from 18.7 nmol/L at age 40 years to 24.5 nmol/L at age 88 years. This increase in variation with increasing age demonstrates that reference ranges for TT that do not take chronological age into account are inappropriate for the assessment of an individual’s testosterone levels. *Our model is derived from data from multiple sources of the measurement of TT in over 10,000 healthy males aged between 3 and 101 years. This is both a strength and weakness of the study. The strength is that modeling power is increased by the provision of large numbers of data points for a wide range of ages: it has been previously shown that models that include both prepubertal, pubertal, and adult ages can be used to derive important insights for a restricted age range [47]. [B]The weakness is the approximate heterogeneity of the values obtained from diverse sources, especially as assay conversion factors were used that have known high correlation but are nevertheless inexact. This includes studies that involve convenience samples (e.g. primary care and outpatient attendees) as well as those that involve population-derived cohorts. Further limitations of our approach are that insufficient data were found to model accurately neonatal ages and that we had to exclude potentially useful studies that used in-house assays which lack standardization and harmonization, and for which no conversion formula has been published [48].[/B] [B]Ten of the thirteen studies used as data sources (Table 1) excluded subjects taking medication that could affect the endocrine system, but three studies [5,6,49] (combined n = 2,371 of 10,097) do not have equivalently explicit inclusion criteria. [U]We can therefore not rule out the possibility that a small number of subjects were on medication that increased their TT levels[/U].[/B][/I] [B]Figure 4. The validated model. Our dataset (n = 10,098) of observed total testosterone for ages 3–88 years, split into normative ranges determined by mean predicted values (blue line) and one (red), two (blue), three (green), and four (purple) standard deviations higher and lower than the predicted values. doi:10.1371/journal.pone.0109346.g004 [ATTACH type="full" alt="Screenshot (10326).png"]19021[/ATTACH] Figure 5. The validated model in centiles. Normative ranges for the model of total testosterone from ages 3–88 years. In the average case (red line) total testosterone remains constant for age .40. However, the variance in normative ranges increases for these ages, with 1st to 99th centile ranges of 5.6–27.6 nmol/L at age 35 years and 4.1–33.1 nmol/L at age 88 years. doi:10.1371/journal.pone.0109346.g005 [ATTACH type="full" alt="Screenshot (10323).png"]19022[/ATTACH][/B] [/QUOTE]
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