I was able to come up with a table using the predictive model equation derived from data in this study:
The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men
The graphs shown in the study (They injected several doses of testosterone enanthate in young and older men) show sensitive estradiol and DHT at different total testosterone blood levels. The curves reach a pseudo plateau at higher TT levels. Older men tended to produce more estradiol and DHT than younger men.
The equation I used was based on a mathematical model shown in this study that included variables calculated from Michaelis-Menten kinetics.
For older men:
E2 (regular immunoassay- not sensitive)= 138.3xTT/(1470.1+TT)
DHT = 269.4xTT/(2389.6+TT)
TT= Total Testosterone
Here is the table I came up with for older men
Of course, as you can see from the graphs above, there is a lot of variability in values, so these predicted numbers are just representing the curve.
CLICK HERE TO CALCULATE THE EXPECTED DHT, E2, AND FREE T FROM A TOTAL T VALUE
Since these estradiol values were immunoassay-based, sensitive (LC/MS) values would be lower. How much lower? We don't know since CRP values were not measured. I would multiply the estradiol numbers in the above table by 0.80 to arrive at a guess for sensitive estradiol values.
These were the baseline characteristics of both groups before they received testosterone enanthate injections. Both groups seemed relatively lean to me.
Treatment protocol:
MAIN MESSAGE: ESTRADIOL AND DHT "NORMAL RANGES" SHOWN BY LABCORP OR QUEST ARE DERIVED FROM MEN WHO DO NOT HAVE HIGH TESTOSTERONE. MANY MEN ON TRT USUALLY HAVE "HIGHER" TESTOSTERONE THAN "NORMAL", SO THOSE RANGES DO NOT APPLY TO THEM. STOP OBSESSING!
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Critical takeaways include:
The higher rate of aromatization in older men is partly attributed to increased adipose tissue (which contains aromatase) and higher SHBG levels. When adjusted for fat mass and SHBG, the differences in free E2 levels between young and older men become statistically insignificant.
The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men
Summary
This video discusses a research paper that explores the effects of different testosterone doses on estradiol and DHT levels in men. The study involved young and older men receiving weekly injections of testosterone for five months. The researchers measured estradiol and DHT blood levels and analyzed the data.Highlights
- The study examined the impact of various testosterone doses on estradiol and DHT levels in men.
- The research involved young and older men who received testosterone injections for five months.
- The study measured estradiol and DHT blood levels to understand the effects of testosterone doses.
The researchers used a mathematical model to predict estradiol and DHT levels based on testosterone doses.- The findings showed that estradiol levels increased with higher testosterone doses, especially in older men.
- DHT levels also increased with testosterone doses but not as significantly as estradiol.
- The study suggests that testosterone replacement therapy may require individualized monitoring of estradiol and DHT levels.
The graphs shown in the study (They injected several doses of testosterone enanthate in young and older men) show sensitive estradiol and DHT at different total testosterone blood levels. The curves reach a pseudo plateau at higher TT levels. Older men tended to produce more estradiol and DHT than younger men.
The equation I used was based on a mathematical model shown in this study that included variables calculated from Michaelis-Menten kinetics.
For older men:
E2 (regular immunoassay- not sensitive)= 138.3xTT/(1470.1+TT)
DHT = 269.4xTT/(2389.6+TT)
TT= Total Testosterone
Here is the table I came up with for older men
Of course, as you can see from the graphs above, there is a lot of variability in values, so these predicted numbers are just representing the curve.
CLICK HERE TO CALCULATE THE EXPECTED DHT, E2, AND FREE T FROM A TOTAL T VALUE
Since these estradiol values were immunoassay-based, sensitive (LC/MS) values would be lower. How much lower? We don't know since CRP values were not measured. I would multiply the estradiol numbers in the above table by 0.80 to arrive at a guess for sensitive estradiol values.
These were the baseline characteristics of both groups before they received testosterone enanthate injections. Both groups seemed relatively lean to me.
Treatment protocol:
MAIN MESSAGE: ESTRADIOL AND DHT "NORMAL RANGES" SHOWN BY LABCORP OR QUEST ARE DERIVED FROM MEN WHO DO NOT HAVE HIGH TESTOSTERONE. MANY MEN ON TRT USUALLY HAVE "HIGHER" TESTOSTERONE THAN "NORMAL", SO THOSE RANGES DO NOT APPLY TO THEM. STOP OBSESSING!
________________________________
Analysis of Testosterone Dose-Response and Conversion to Estradiol and Dihydrotestosterone
Executive Summary
This briefing document synthesizes findings from clinical research and expert analysis regarding the conversion of testosterone (T) into its active metabolites: 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT). Based on the study by Lakshman et al. (2010) and subsequent synthesis by health experts, the data indicates that both E2 and DHT levels increase dose-dependently with testosterone administration but follow saturable Michaelis-Menten kinetics.Critical takeaways include:
- Age-Related Variations: Older men exhibit significantly higher rates of whole-body aromatization (conversion to E2) compared to younger men, largely due to higher percentage fat mass and Sex Hormone-Binding Globulin (SHBG) levels.
- Saturable Kinetics: The conversion processes for both E2 and DHT reach a pseudo-plateau at higher testosterone doses, meaning E2 and DHT do not increase indefinitely or linearly as testosterone levels rise.
- Clinical Relevance of Lab Ranges: Standard "normal ranges" provided by major laboratories (e.g., Quest, LabCorp) are typically derived from men with lower testosterone levels. Consequently, these ranges are often inadequate for evaluating men on Testosterone Replacement Therapy (TRT) who maintain higher-than-average testosterone concentrations.
- Assay Specificity: Conventional immunoassay-based E2 tests may overstate levels due to interference from factors like C-reactive protein (CRP), necessitating the use of sensitive (LC/MS) testing for accurate clinical assessment.
Detailed Analysis of Testosterone Metabolites
1. Dose-Dependent Response and Conversion
The administration of graded doses of testosterone enanthate (TE) results in a clear dose-dependent increase in both serum E2 and DHT. However, these increases are not linear.- Estradiol (E2): Produced via peripheral aromatization of testosterone, primarily in adipose tissue. Both total and free E2 increase as the testosterone dose rises.
- Dihydrotestosterone (DHT): Derived via 5α-reduction of testosterone. While DHT levels increase with higher testosterone doses, the increase is less significant than that observed with E2.
- Ratios: Interestingly, the E2:T and DHT:T ratios actually decrease as testosterone doses increase, reflecting the saturable nature of the converting enzymes (aromatase and 5α-reductase).
2. The Impact of Aging on Hormonal Conversion
Age is a primary factor in how the body processes exogenous testosterone. The research identifies distinct differences between young men (ages 18–35) and older men (ages 59–75).| Variable | Young Men Response | Older Men Response |
| Aromatization Rate | Lower maximal rate (Vmax). | 40% higher Vmax than younger men. |
| E2 Levels | Lower total and free E2. | Higher total and free E2. |
| E2:T Ratio | Lower ratio. | Significantly higher ratio. |
| DHT Levels | Higher at baseline; similar on-treatment. | Lower at baseline; similar on-treatment. |
| Body Composition | Lower BMI and fat mass. | Higher BMI, fat mass, and SHBG. |
The higher rate of aromatization in older men is partly attributed to increased adipose tissue (which contains aromatase) and higher SHBG levels. When adjusted for fat mass and SHBG, the differences in free E2 levels between young and older men become statistically insignificant.
3. Mathematical Modeling of Conversion Kinetics
The study employed Michaelis-Menten kinetics to model how testosterone is converted into its metabolites. This model uses two primary parameters: Km (the substrate concentration at which the reaction rate is half of Vmax) and Vmax (the maximum reaction rate).- Aromatase (T to E2): The estimated in vivo Km for aromatase is 1.83 nM, a value that remains independent of age. However, the Vmax is significantly higher in older men.
- 5α-reductase (T to DHT): The estimated in vivo Km is 3.35 nM. The maximal whole-body production rate (Vmax) for DHT does not appear to be affected by age.
- Saturability: Because these processes are saturable, the curves for E2 and DHT reach a "pseudo plateau" at high total testosterone (TT) levels.
Predictive Equations for Older Men
Based on the Michaelis-Menten model, the following equations can be used to predict hormone levels in older men:- E2 (Immunoassay): 138.3 \times TT / (1470.1 + TT)
- DHT (ng/dL): 269.4 \times TT / (2389.6 + TT) (Note: To estimate "sensitive" LC/MS E2 levels, a reduction of approximately 20% from the immunoassay result is suggested.)
Clinical Implications and Laboratory Standards
Inadequacy of Standard Reference Ranges
A central conclusion of the analyzed context is that the "normal ranges" for E2 and DHT provided by commercial labs are often misleading for TRT patients. These ranges are derived from a general population with "normal" (often lower) testosterone levels. Men on TRT frequently maintain testosterone levels at the high end of, or above, the standard range; therefore, their E2 and DHT levels will naturally be "high" according to standard reference intervals without necessarily indicating a clinical pathology.Assay Sensitivity and Interference
The method of testing significantly impacts the reported E2 value.- Immunoassay (RIA): These tests are known for reduced specificity, particularly at lower concentrations. Evidence suggests that C-reactive protein (CRP) or associated inflammatory factors can interfere with immunoassays, causing them to overstate E2 levels.
- Mass Spectrometry (LC/MS): Often referred to as "sensitive" or "ultrasensitive" testing, this is the gold standard. It correlates moderately with immunoassays but is not susceptible to the same inflammatory interference.
Clinical Management Observations
- Gynecomastia: High doses of testosterone are occasionally associated with gynecomastia. While E2:T ratios actually decrease at high doses, the absolute concentration of E2 may reach levels sufficient to trigger the condition.
- Estrogen Thresholds: While very low E2 is linked to bone loss, fracture risk, and cognitive decline, excessively high E2 has been associated in some studies with stroke and metabolic syndrome. The research suggests a need for individualized monitoring rather than adhering to rigid, population-based ranges.
- Inflammation: Because CRP can artificially inflate immunoassay E2 results, clinicians should be wary of "high" E2 readings in patients with systemic inflammation.
Study Methodology and Baseline Data
The findings are derived from a five-month study involving 51 young men and 52 older men.- Suppression: Endogenous testosterone was suppressed using a monthly GnRH agonist (leuprolide depot, 7.5 mg).
- Administration: Participants received weekly injections of testosterone enanthate at randomized doses (25, 50, 125, 300, or 600 mg).
- Testing: Hormone levels were measured at steady-state (days 84 and 112) exactly seven days after the previous injection.
- Baseline Differences: At the start of the study, older men had lower total and free testosterone and higher SHBG compared to younger men. Older men also possessed higher fat mass (22.3 kg vs. 14.4 kg in younger men).
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