Testosterone to estradiol ratio reflects inflammation and predicts future cardiovascular events in men

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Nelson Vergel

Founder, ExcelMale.com
Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis

Cardiovascular Research, cvy188, Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis
Published: 20 July 2018

The effects of testosterone on cardiovascular disease (CVD) as reported in literature have been ambiguous. Recently, the interplay between testosterone and oestradiol as assessed by testosterone/oestradiol (T/E2) ratio was suggested to be better informative on the normal physiological balance. Considering the role in CVD, we hypothesized that a low T/E2 ratio in men with CVD is associated with increased inflammation, a more unstable plaque and a worse cardiovascular outcome.

Methods and results
Testosterone and oestradiol concentrations were determined in blood samples of 611 male carotid endarterectomy patients included in the Athero-Express Biobank Study. T/E2 ratio was associated with baseline characteristics, atherosclerotic plaque specimens, inflammatory biomarkers, and 3 year follow-up information. Patients with low T/E2 ratio had more unfavourable inflammatory profiles compared with patients with high T/E2 as observed by higher levels of C-reactive protein [2.81 μg/mL vs. 1.22 μg/mL (P < 0.001)] and higher leucocyte counts [8.98*109/L vs. 7.75*109/L (P = 0.001)] in blood. In atherosclerotic plaques, a negative association between T/E2 ratio and number of neutrophils [B = −0.366 (P = 0.012)], plaque calcifications [OR: 0.816 (P = 0.044)], interleukin-6 (IL-6) [B = −0.15 (P = 0.009)], and IL-6 receptor [B = −0.13 (P = 0.024)] was found. Furthermore, in multivariate Cox regression analysis, low T/E2 ratio was independently associated with an increased risk for major cardiovascular events (MACE) during 3 year follow-up [hazard ratio 1.67 (95% confidence interval 1.02–2.76), P = 0.043]. In men with elevated body mass index (BMI), these effects were strongest.

In male patients with manifest atherosclerotic disease, low T/E2 ratio was associated with increased systemic inflammation, increased inflammatory plaque proteins, and an increased risk of future MACE as compared to men with normal T/E2 ratio. These effects are strongest in men with elevated BMI and are expected to be affected by aromatase activity in white fat tissues. Normalization of T/E2 ratio may be considered as target for the secondary prevention of CVD in men.

CVD, Inflammation, Atherosclerosis, Testosterone, Oestradiol, Ratio, Survival, Plaque
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Nelson Vergel

Founder, ExcelMale.com
My position is that most men should not be using anastrozole unless there is something wrong with your aromatase. The 20-45 E2 range has been derived from men with low to moderate testosterone, not for men on TRT with higher levels. Since 0.3% of T aromatizes to estradiol, expecting a man with a T of 500 to have the same E2 as a man with a T of 1000 is dumb. Screwing with the estradiol receptors is also not a very smart thing to do. Estradiol, like DHT, are boosters of testosterone effects, not toxic byproducts. Our obsession to relate all bad things to a "female" hormone that "does not belong in a male body" is as bad as doctors' obsession with thinking that testosterone is bad for women. Estradiol is key for proper brain function, cardiovascular health, strong bones, erectile function, and proper body composition, among other benefits. Even the fear of gynecomastia in men on TRT is unfounded since gyno usually occurs when low T, high IGF-1, high E2, and genetics are all combined. I think hormone ratios are one step above the single hormone mentality that forgets that most hormones interact with each other, especially those in the same hormone tree. I have pretty much given up repeating the same message after 10 years since there is nothing I can do to combat the misinformation out there on estradiol. The E2 obsession fills this site I created!

I have written many articles and done many videos. Take the time to go through all pages of this thread that most people do not read.

Role of Estradiol in Men and Its Management
As long as this isn't factoring in SHBG and how it binds to, or not, to E just like it does to T, this is all very flawed and frankly it seems more and more of an out of date position to hold on to, a ratio of T:E.


Though it is very notable the E symptoms that present themselves can be viewed as very tolerable for some, to almost transparent sense. Such as me feeling warm or too hot or sweaty in bed can seem to be a very benign thing to many guys, but for me, it disrupts my sleep for 1-2-3 hours a night which THAT becomes the very problematic part.

Im doing the best I've been to this point, I've had multiple negatives resolve themselves with my trough LC/MS/MS in the single digits. My SHBG is consistently in ~12 range. Save for one lingering issue I'd be a very happy man.

Nelson Vergel

Founder, ExcelMale.com
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