Testosterone and E2 are good for the Heart.

[Guest guest]

I just got this in my Email from Dr. Dach.

http://jeffreydach.com/2010/12/31/pr...frey-dach.aspx

So it looks like being on TRT and having a bit of a problem with E2 from this is

good for your heart.

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Preventing and Reversing Heart Disease, Part Three

by Dach MD

A Man with Progressive Coronary Artery Disease Unresponsive to Statins

62 year old Jim came to see me after his third cardiac stent in 10 years. About

a year ago, Jim noticed a " tight feeling " in his chest radiating to his throat,

was rushed to the ER, and doctors found he was having a heart attack. A coronary

angiogram showed extensive coronary artery disease with irregular plaque

formation virtually everywhere in his arteries. For the past 10 years, Jim had

been under the care of top cardiologists who prescribed a statin cholesterol

drug, and Jim's cholesterol was kept below 140 all this time. Jim's heart

disease progressed relentlessly in spite of the low total cholesterol numbers

clearly showing another cause at work here. It's obviously not the total

cholesterol.

Doctors advise Jim to Stop Testosterone

Jim had been taking testosterone topical gel for the past 5 years, and recently

stopped it because of advice from his cardiologist who pointed a finger and

said, " You should stop the testosterone. The testosterone is bad for your heart

and probably caused your heart attack " . Jim came to see me for a second opinion.

Our Approach

I must preface these remarks with our approach to prevention and reversal of

heart disease which is outlined in Part One and Part Two of this series. We

credit and rely heavily on the " Track Your Plaque Program " by MD.

Bioidentical Hormones For Prevention and Reversal of Heart Disease

In this article we will revisit the role of the testosterone and estradiol in

prevention and reversal of heart disease, looking at the latest research.

Firstly, let's examine the hypothesis peoposed by Jim's doctor that Testosterone

is somehow " bad " for men with heart disease.

Low Testosterone is Predictive for Increased Mortality from Heart Disease

If Jim's Doctor's advice was right, one would expect that men with high

testosterone should have more heart disease, and men with low testosterone

should have less heart disease. This is exactly opposite of four major studies

that show men with low testosterone have increased all-cause mortality and

increased heart disease mortality(1-4)

Testosterone Levels in Men With Heart Disease

A recent study by Malkin looked at Testosterone levels in men with known

underlying heart disease. He showed that low Testosterone is common in men with

underlying heart disease, and this is associated with almost double the

mortality rate. (5) Again these findings suggest that higher Testosterone is

protective and prevents progression of heart disease. The assumption that

Testosterone is somehow deleterious to the heart has been shown false.(6-9).

Above image: Cross section of arteries (left to right) showing development of

fatty streak which enlarges into the atherosclerotic plaque.

Animal Studies on Mechanism of Protection

A number of elegant animal studies have been done to elucidate the mechanism by

which Testosterone is protective of heart disease. A 1999 study by sen

in rabbits showed that testosterone reduced aortic atheroscleosis. Castrated

rabbits had low testosterone levels and significant increase of 100% in aortic

atherosclerosis suggesting that testosterone has a strong preventive effect on

male atherosclerosis. In the groups receiving testosterone or DHEA they found

marked inhibition of atherosclerosis compared with placebo. The mechanism was

not clearly defined. They speculated on a non-lipid mediated mechanism, possibly

related to aromatase conversion of testosterone to estrogen. (10 )

In an elegant 2001 study published in PNAS, et al used a mouse model of

accelerated atherosclerosis to show that Testosterone inhibits atherosclerosis

by conversion to estradiol by the aromatase enzyme. Similar protection from

atherosclerosis was obtained by administering estradiol. In addition, blocking

conversion of testosterone to estradiol with the aromatase inhibitor,

anastrazole, eliminated the protective effect and these animals showed

pregressive atherosclerosis.(11)

Dr suggested that " testosterone attenuates early atherogenesis most

likely by being converted to estrogens by the enzyme aromatase expressed in the

vessel wall " . This information suggests that men with heart disease should NOT

take arimidex (anastrazole) along with their testosterone replacement therapy.

These findings were confirmed by Nettleship in a 2007 study published in

Circulation using the Tfm Mouse. This is a mouse geneticlly altered to have a

defective androgen receptor. In these mice, Testosterone cannot work through its

normal genomic pathway, since there is no receptor. In spite of the lack of

androgen receptor, Nettleship found that testosterone replacement in these mice

attenuated atherosclerotic changes (fatty streak formation), suggesting the

protective effect of testosterone was independent of the testosterone receptor.

The authors concluded that the protective benefits of testosterone were through

aromatase conversion to estradiol, and then via the estrogen receptor

pathways.(12)

Dr Nettleship's findings were confirmed by Bourghardt in a Nov 2010 study

published in Endocrinology which using " ARKO " mice, genetically modified to

" knock out " the Androgen Receptor, as well modified to be Apo-E deficient (to

accelerate atherosclerosis). The authors showed that Testosterone therapy

admistered to the ARKO mice inhibited atherosclerosis. However inhibition of

atherosclerosis was more profound in the wild type mice that still had intact

androgen receptors. The authors concluded the mechanism of protection of

testosterone was due to both mechanisms, through the Androgen Receptor as well

as through aromatase conversion to estradiol.(13 )

Conclusion: These animal studies suggest that testosterone's cardio-protective

benefits are due (at least in part) to conversion to estrogen, and that estrogen

is the cardioprotective agent. Both estrogen and testosterone are bioidentical

hormones. Clearly the message here is Testosterone Replacement Therapy should be

an important part of any heart disease prevention program in those patients who

are clinically symptomatic and are found to have low Testosterone levels.

Why Do Men Have More Heart Disease Than Women ?

Men and women are quite different when it comes to heart disease. Men have more

than twice the risk of dying from coronary disease than women. (14) In women,

coronary artery disease (CAD) develops on average 10 years later than in

men.(15) Could higher levels of estrogen (estradiol) in women explain the

protection enjoyed by women?

Dr Xing from the University of Alabama would say, yes of course. In a 2009

article, Dr Xing names a number of mechanisms by which estradiol protects both

men and women from heart disease. He says, " estrogens have antiinflammatory and

vasoprotective effects. Natural endogenous estrogen 17â-estradiol (bioidentical)

has been shown to cause rapid endothelium-independent dilation of coronary

arteries of men and women, to augment endothelium-dependent relaxation of human

coronary arteries, and improve endothelial function...Observational studies have

shown substantial benefit (50% reduction in heart disease) of hormone therapy in

women who choose to use menopausal hormones. " (15 )

Estrogen is Protective of Heart Disease

A 2010 study in European Heart by Kitamura et al compared males to female heart

attack rates. They found 61% fewer heart attacks in women of reproductive age

with high estrogen levels compared to males of the same age. The authors

conclude that estrogen confers cardioprotective benefits.(16) A review of the

Nurse Health Study published in the 2000 ls showed 40% reduction in heart

disease in hormone replacement users and that " postmenopausal hormone use

decreases risk for major coronary events. " (17 ) (18)

Comparing The Three Treatment Modalities for Heart Disease

There are three mainstream treatment modalities for coronary artery disease.

1) Surgery with coronary artery bypass.

2) Balloon angioplasty with stenting.

3) Medical Therapy with drugs such as calcium channel blockers and beta

blockers.

Which one of these treatment modalities confers the most benefit? The answer is:

none of them. Medical managment with drug treatment gives the same benefit as

stenting. Eleven randomized studies reviewed 3,000 patients with stable coronary

artery disease. Treatment with angioplasty and stenting showed the same

mortality and heart attack rate as drug treatment (also known as medical

management). They both offer the same benefit.(19)(20)

The MASS II study published in the 2007 Circulation showed medical managment

with drugs to have similar outcome to stent or bypass. (21) A troubling fact

remains that after all these studies have been completed, there is no conclusive

evidence that intervention with CABG (coronary artery bypass graft) or coronary

stent is superior to medical therapy (drugs) for treating multivessel coronary

artery disease with stable angina and preserved ventricular function.(21 )

Sorano attempts to sort out the fine points of selecting between treatment

modalities in her 2009 report. (22)

How Can Drugs Provide the Same Outcome as Surgery or Stenting?

The EPC.

Now we have an important question to ask. How is it possible that the humble

country doctor with a few drugs can provide similar outcomes when compared to

the high and mighty cardiac surgeon and the interventional cardiologist? How can

drug treatment do as well or better than the cardiac stent or surgical bypass

procedure?

I suggest the answer resides in the phenomenon known as " collateral vessel

formation " . The heart has the ability to grow new blood vessels which provide

blood flow around the blocked artery. Medical treatment gives the heart time to

grow new collateral vessels. The key to understanding this new vessel formation

is the endothelial progenitor cell, also known as the EPC. The EPC is a special

type of stem cell found in the bone marrow that circulates to injured myocardium

where they promote local angiogenesis, making new blood vessels. (23)

Turning On The Endothelial Progenitor Cell - How to Do It?

A previous article on telomeres and anti-aging discussed the role of estrogen as

an activator of telomerase which serves as an anti-aging therapy. Recent

research shows that estrogen activates the telomeres on endothelial progenitor

cells and improves the EPC functional capacity. (24) Another study showed

reduced numbers of EPC cells in the peripheral blood of men with low

testosterone levels. (25)

Estradiol Enhances Recovery After Myocardial Infarction - Collateral Vessels

An elegant mouse study was published by Isakura in 2006 Circulation . They used

a mouse model in which myocardial infarction (heart attack) was induced by

ligation of the left coronary artery. The estradiol treated mice showed

increased circulating EPC's and greater capillary density in the recovering

myocardium. This indicates enhanced recovery in the estradiol treated mice by

regrowth of collateral vessels. (26)(27)(28) A study from Bolego in Italy showed

that the cardio protective benefits of estrogen could be duplicated with an

estrogen receptor drug called PPT. They found that " myocardial

ischemia-reperfusion injury was exacerbated by ovariectomy (which reduced

estrogen levels). This injury returned to baseline following treatment with

estrogen-like drug PPT. " The protective effects were linked to increased levels

of endothelial progenitor cells (EPCs).(29)

Conclusion

Recent research shows the cardioprotective benefits of the bioidentical

hormones, testosterone and estrogen. Testosterone benefits appear mediated

through its conversion to estradiol via the aromatase enzyme. Estradiol's

benefits appear derived at least in part in the ability of estradiol to activate

the Endothelial Progenitor Cells and invoke new collateral circulation in areas

of injury.