How to Predict Estradiol and DHT at Different Testosterone Doses

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

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!

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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.

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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.)

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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.

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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).

 

Thanks @ecdysone

 

Guys, my last test came back at 1169 and my ultra-sensitive estradiol came back at 66. Would any of you be concerned?

 

Guys, my last test came back at 1169 and my ultra-sensitive estradiol came back at 66. Would any of you be concerned?

how u feeling mood and energy wise? How’s libido and erections?

 

how u feeling mood and energy wise? How’s libido and erections?

I feel great! Getting great results with putting on muscle and losing fat - I'm hard when I need to be and waking up with morning wood. I just don't want GYNO!!!!

 

I feel great! Getting great results with putting on muscle and losing fat - I'm hard when I need to be and waking up with morning wood. I just don't want GYNO!!!!

I wouldn’t worry about gyno at all. U’ll know if u have to worry about it. When I was using HCG monotherapy I started to develop some gyno in my left nipple. I’m assuming it was mostly due to the increase in prolactin and/ or progesterone tho, because I’ve had my E2 way higher on TRT, and never had any issues with gyno. Before the gyno started to form on HCG mono, my nipples were constantly itchy and sensitive for weeks and weeks. They were so itchy and sensitive that I had to put tape over them so they wouldn’t rub up against my shirt. I would scratch them to the point they would start to bleed a little bit. On testosterone I’ll get random nipple sensitivity for a day or two during hormone fluctuations, but nothing even remotely close to what I experienced on HCG mono prior to getting gyno. I now can recognize the difference between hormone fluctuation nipple sensitivity and gyno forming nipple sensitivity. So unless ur nipples end up being itchy and sensitive for weeks on end, I wouldn’t worry about getting gyno from an elevated E2

 

T 637
E 32
E compativel com a tabela, se reduzi-lo 20%

 

I had my last bloods done with Quest was at 1411 Total Test, Estradiol 67 ( Reference Range < 39. I am taking DIM-300 dose. This table is right on the money.

 

I wouldn’t worry about gyno at all. U’ll know if u have to worry about it. When I was using HCG monotherapy I started to develop some gyno in my left nipple. I’m assuming it was mostly due to the increase in prolactin and/ or progesterone tho, because I’ve had my E2 way higher on TRT, and never had any issues with gyno. Before the gyno started to form on HCG mono, my nipples were constantly itchy and sensitive for weeks and weeks. They were so itchy and sensitive that I had to put tape over them so they wouldn’t rub up against my shirt. I would scratch them to the point they would start to bleed a little bit. On testosterone I’ll get random nipple sensitivity for a day or two during hormone fluctuations, but nothing even remotely close to what I experienced on HCG mono prior to getting gyno. I now can recognize the difference between hormone fluctuation nipple sensitivity and gyno forming nipple sensitivity. So unless ur nipples end up being itchy and sensitive for weeks on end, I wouldn’t worry about getting gyno from an elevated E2

Could also be the ratio between androgens and e2.

 

I had my last bloods done with Quest was at 1411 Total Test, Estradiol 67 ( Reference Range < 39. I am taking DIM-300 dose. This table is right on the money.

How does one feel?

 

Could also be the ratio between androgens and e2.

Vey good point! But idk, I was controlling E2 with an ai, and test levels were around 1200 total on 2000iu’s of HCG/ week. But honestly there’s still a chance u could be right. HCG stimulates the leydig cells in the testicles to produce testosterone, and I’ve heard that HCG causes a lot of the aromatizatiin to occur within the testicles, and I’ve heard that ai’s are inneficient/ unable to control testicular aromatization, or something along those lines. So the point u brought up could definitely be valid. Good thinking

 

With 1200 total test e2 would need to be very high to have gyno for most. You may be right about prolactin. I’ve heard that prolactin is a good metric for tissue estrogen but I cannot remember the literature. Maybe I can dig it

the benefit of hcg is that there should also be a nice increase in progesterone which prevents estrogen from being stored in tissues. This is likely why hcg increases e2 more. It’s because it increases progesterone and higher progesterone means more circulating e2 vs tissue bound.

progesterone should lower prolactin over the long run.

Maybe this is why progesterone causes sexual sides for some. I’d venture to say it’s temporary and could be due to a change in how e2 is behaving in the presence of progesterone until such time the body adjusts.

 

Hi @Nelson Vergel , thanks for the video and calculation! I have watched it twice but for some reason just cant get my head around it, sorry mate. I am 29 years old fyi, what should my oestradiol be roughly with your graph?

So my serum oestradiol level is 15.23 pg/ml.
My testosterone is 527.8 ng/dl

So do I now divide the 2?

 

1 Picogram per milliliter [pg/ml] = 0.1 Nanogram per deciliter [ng/dl]

Estradiol 15.23 pg/mL= 1.523 ng/dL

Estradiol ng/dL/Total T ng/dL x 100= 1.523/527.8= 0.00288. So, you multiply 0.00288 x 100= 0.288%. You are aromatizing 0.288% of your total T into Estradiol. We have some data that shows 0.3- 0.4% of T gets aromatized to estradiol, so you are under that (assuming you are not taking anastrozole).

For a T/E2 ratio;

527.8/15.23= 34.7

The only data we have is about low fertility with low T/E2 ratios under around 14. So, you are good.

 

Any idea why my dht would be way off based on this formula ? FYI it’s twice the range with a pretty moderate tt

 

Any idea why my dht would be way off based on this formula ? FYI it’s twice the range with a pretty moderate tt

What's your DHT? It usually runs about 10% of total T.

This is the formula from the study:

DHT = 269.4xTT/(2389.6+TT)

TT= Total Testosterone

 

What's your DHT? It usually runs about 10% of total T.

This is the formula from the study:

DHT = 269.4xTT/(2389.6+TT)

TT= Total Testosterone

Using that formula my dht should be 61, I typically come in around 170. This is just on injections and hcg. When I used the gel my levels were 275

 

@Graham

You are probably one of the outliers.

 

@Graham

You are probably one of the outliers.


View attachment 17882

Interesting, should I be worried about having dht levels high like mine long term ?

 

Interesting, should I be worried about having dht levels high like mine long term ?

Not really. Enjoy it.

Read this review:

Is Dihydrotestosterone DHT Good or Bad for Men? - Excel Male Health Forum

In this issue of Endocrine Reviews, Swerdloff et al. (5) review the human and animal data regarding the physiological and clinical implications of elevated blood concentrations of DHT in men and women. All exogenous testosterone formulations increase serum DHT concentrations above...

www.excelmale.com

 

I also have similar E levels, and my endo is also very hesitant to up my dose, and my T levels were still very high on Spyro (above the upper male limit with 100 mg/day), so I changed to cypro. I'm not the only one, and I know other people that Spyro didn't work, who knows why. I think a dose of 600-800 mg/day is overkill, I haven't seen anyone with doses higher than 400 mg, and the normal one is around 100-200 mg, so try to ask your doctor to try another blocker. I'm also on steroids, found safer alternatives for these supplements on [edited by moderator].