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Estradiol and HDL

One interesting protocol change that I have observed on the Peak Testosterone Forum of late is that some of the guys on HRT are saying that their doctors want their estradiol quite high. "More is better" seems to be the philosophy with these physicians. Now I am very skeptical of that position for many reasons:

  • High estradiol in men has been linked in one study to increased mortality
  • Many men on the Peak Testosterone Forum have said they did much better when their estradiol fell into the 20-30 pg/ml range.
  • Higher estradiol levels possibly contribute to a number of prostate issues, such as BPH and cancer.
  • Higher estradiol levels have many of the same symptoms as low testosterone and some new ones, such as gyno and water retention
  • Higher estradiol levels can negatively impact clotting and potntially lead to greater chance of clotting and strokes
  • In spite of all these negatives, these doctors wanting higher estradiol levels do have an interesting point: estradiol is incredibly important according to recent research for arterial health. In fact, one study showed that IMT (intima media thickness) scores, i.e. arterial plaque levels, were tied to estradiol levels. The authors concluded:

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    "Circulating E2 is a predictor of progression of carotid artery intima-media thickness in middle-aged men. Further studies are needed to investigate the role of endogenous E2 for incident cardiovascular disease events." [1]

    Men have the idea that estradiol, being the chief estrogen is "bad,"  because it is the "female hormone."  Well, the truth is that you desperately need a certain amount of estradiol in order for arteries to be healthy and on this page we are going to look at one reason why:  estradiol is a stimulator of HDL, the good cholesterol that shuttles cholesterol out of foam cells.  Researchers have long known that women, who have higher estradiol levels than men of course, enjoy improved and increased HDL levels.  So the question is whether or not the same effect would be seen in men as well.

    NOTE:  Again, you do not want to be "deficient" in estradiol.  For the many reasons, see my page Do Men Really Need Estrogen, Especially Estradiol? for more information. 

    To test this theory on men, researchers did an involved study where they suppressed testosterone levels and then artificially increased them with testosterone enanthate (an ester similar to cypionate). They then suppressed the conversion of testosterone to estradiol pharmaceutically.  What was the purpose of all of this?  It left the participants with youthful testostereone but very low estradiol levels. And doing all this verified their thesis:

    "Plasma HDL cholesterol, particularly, the HDL2 fraction, decreased significantly in response to the low serum E2 level...Only a small decrease in HDL2 cholesterol was seen in these men. There were no hormonal or lipid changes in the placebo group. We conclude that in men, physiological levels of E2 [estradiol] are important in maintaining plasma levels of HDL cholesterol, especially the HDL2 fraction. " [2]

    So this study directly confirmed the idea that estradiol increase HDL.  However, one concern that researchers have is that you don't want to increase HDL unless the quality also increases.  It turns out that you can increase HDL and actually make it pro-oxidant to where it does not do it's cholesterol transporting job.  One study showed that this was indeed the case: estradiol lead to the incorporation of serum amyloid A (SAA) into the HDL, which actually turns your good cholesterol from friend into foe. This ugly turn of events can create a "franken-HDL" that would increase plaque instead of decrease it. [3] Indications of these issues were shown in a study on men with chronic heart failure, where participants with estradiol greater than 37 pg/ml had more than double the risk of dying. [4]

    There is yet another "cardiovascular dark side" to estradiol increases:  estradiol generally raises CRP (C-Reactive Protein) and other inflammatory markers. [3] This may negate any cardiovascular benefit when artificially elevated.  Many women, for example, are not allowed estradiol creams (for post-menopause, etc.) over clotting concerns.  Although men have much lower levels of estradiol, the concerns still remain. 

    All of this means that, while estradiol does increase HDL, it is highly debatable as to whether or not it is wise to just let estradiol go overly high.  This is a real issue for men on HRT, whose estradiol often goes very high due to the increase in testosterone coupled with being overweight.  (Fat contains aromatase, the enzyme that convert testosterone to estradiol.)

    NOTE:  Does testosterone affect HDL?  Read my page on Testosterone and HDL for additional information.

     

    REFERENCES::

    1)  JCEM, 91(11), Received: May 02, 2006, Accepted: August 17, 2006, Published Online: July 02, 2013, "Circulating Estradiol Is an Independent Predictor of Progression of Carotid Artery Intima-Media Thickness in Middle-Aged

    2) JCEM, Published Online: July 01, 2013, "Physiological levels of estradiol stimulate plasma high density lipoprotein2 cholesterol levels in normal men"

    3) Arteriosclerosis, Thrombosis, and Vascular Biology, 2004, 24: 1741-1742, "Estrogen and HDL: All that Glitters Is not Gold"

    4) JAMA, 2009 May 13, 301(18):1892-901, "Circulating estradiol and mortality in men with systolic chronic heart failure"

    5) J CARDIOVASC PHARMACOL THER, May 2014, 19(3):256-268, "Regulation of Endothelial Nitric Oxide Synthase and High-Density Lipoprotein Quality by Estradiol in Cardiovascular Pathology"

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