Testosterone and Estrogen Balance:
Recent studies suggest that testosterone replacement may improve the symptoms of vascular disease. A placebo-controlled crossover study in men with ischemic disease and low testosterone levels reported that axial-slice time in the times-development of ischemic changes in the treadmill test were both increased with testosterone replacement. It has also been shown that men with lower levels of testosterone have poorer endothelial function. In a study of 875 males, researchers found that those men in the highest quartile of testosterone levels had a 1.7-fold greater flow-mediated dilation, a marker of endothelial function. In another study, researchers examined the correlation between testosterone levels and mortality in over 900 men with coronary heart disease. The team found that the mortality rate in patients with testosterone deficiency was 21% while only 12% of subjects with normal testosterone levels died. The author of the study concluded that (in patients with coronary disease) testosterone deficiency is common (and impacts significantly negatively on survival).
Researches analyzed 30-days’ survival in 126 men who had suffered a heart attack. All the men who did not survive were found to have low testosterone levels. The team went on to conclude that a low level of testosterone was independently related to total short-term mortality.
Testosterone levels are inversely associated with the development of coronary artery disease. In a study of men 45 years of age or younger, researchers found that the subjects with diagnosed coronary artery disease had significantly lower levels of free testosterone than did healthy aged-match controls. The researchers went on to caution that based on their findings “A low level of free testosterone may be related to the development of premature coronary artery disease”.
Italian researchers compared plasma testosterone levels of 119 elderly men with isolated systolic hypertension to those of 106 elderly men without high blood pressure. All the study participants were 60 to 79 years old, not obese, and nondiabetic, and nonsmokers. The hypertensive men were found to have 14% lower testosterone levels compared to normotensive. Low testosterone levels correlated with higher blood pressure.
In a study of over 11,000 men followed for 10 years, baseline testosterone concentrations were inversely associated with cardiovascular and all-cause mortality. Men with total testosterone levels of 481 ng/dL or greater at baseline were significantly less likely to die of cardiovascular disease or any cause during the follow up period, compared to men that had levels of less than 481. The correlation held after adjustment for various co-founding factors. The authors of this study declared that “low testosterone may be a predictive marker for those at high-risk of cardiovascular disease”.
A study published in the Journal of the American Medical Association, JAMA, measured blood estradiol, estrogen levels in 501 men with chronic heart failure. Compared to men in the balanced estrogen, men in the lowest estrogen quintile were more likely to die in the three year follow up, while men in the highest estrogen quintile were 133% more likely to die. The men in the balanced quintile had fewer deaths, those that had serum estradiol levels between 21 and 31.
Testosterone Protects Women, Too
Testosterone is often thought to be only beneficial for men; however, a study of nearly 3000 women revealed that maintaining optimum testosterone levels is important for females. After assessing testosterone levels at baseline, researchers found that over 4.5 years follow up, those women with the lowest levels of testosterone were more likely to experience a cardiovascular event and die of any cause than the women with the highest testosterone. The author concluded “low baseline testosterone in women is associated with an increased all-cause mortality and incident cardiovascular events independent of traditional risk factors”.
Testosterone receptors are present in the endothelium cells, the vascular smooth muscle, and cardiomyocytes. Testosterone acts on the vascular arterial wall where it induces vasodilation. Testosterone induces also protein synthesis and hypertrophy of the cardiomyocytes, and testosterone is also important in myocardial contractility. In heart failure patients, testosterone decreased PVR and afterload, and increased cardiac output. There was improvement in the exercise capacity and functional capacity was also improved. Of importance to note is that insulin resistance also improved and there was an increase in total body mass with a decrease in fat mass.
DHEA
DHEA is a precursor to sexual hormones such as testosterone and estrogen. Levels decline with age, and the decline is associated with the onset of various medical conditions including chronic inflammation, hypertension, and atherosclerosis. Higher levels of DHEA in humans are associated with lower levels of inflammatory bio-markers.
A study showed that men with high levels of DHEA tend to have greater protection against aortic atherosclerosis progression. Similarly, another study of 419 Japanese individuals found those with the highest circulatory levels of DHEA sulfate were much less likely to have carotid atherosclerosis. Animal studies show a protective role in DHEA in preventing atherosclerosis. Providing DHEA to human vascular endothelial cells in culture increases nitric oxide synthesis, which boosts blood flow.
Progesterone
Several studies have determined that NON-BIO-IDENTICAL SYNTHETIC PROGESTIN (not used by this office) promotes the progression of atherosclerosis. The story is quite different for BIO-IDENTICAL NATURAL PROGESTERONE, where multiple animal studies have shown that bio-identical estrogen inhibits the process of atherosclerosis. To illustrate, scientists fed postmenopausal monkeys a diet which is known to cause atherosclerosis, for 30 months. The scientists then divided the monkeys into groups that received estrogen alone, estrogen plus non-bio-identical progestin or a control group that received no hormones. The control group developed substantial atherosclerotic plaque. The administration of estrogen resulted in a 72% decrease in atherosclerotic plaque compared to the control. Treatment with non-bio-identical progestin yielded disturbing results. The group that received estrogen plus combined with non-bio-identical progestin had similar amounts of atherosclerotic plaque as the control, meaning that synthetic progestin completely reversed the positive effects of estrogen in atherosclerosis. In contrast, when the same investigators administered bio-identical progesterone along with estrogen, no such inhibition of estrogen’s cardiovascular effects were seen.
In a trial published in the Journal of the American College of Cardiology, researchers studied postmenopausal women with a history of heart attack or coronary artery disease. The women were given estrogen in combination with either bio-identical progesterone or non-bio-identical progestin. The women on the bio-identical progesterone had increased blood flow and did better on their exercise stress tests.
Estriol
Growing evidence suggests that estriol may offer benefit to the cardiovascular system. In a 12-month study in Japan, there was significant decrease in both systolic and diastolic blood pressure as well as total cholesterol and triglycerides. To examine the effects of estriol on atherosclerosis, a study showed that those given estriol had 75% less atherosclerosis than the group of rabbits fed with a high cholesterol diet alone.
Phytoestrogens
Phytoestrogens are plant hormones with estrogen-like activity. These phytoestrogens have also been shown to improve vascular function, which declines with age.
Low Thyroid Function
T3 from the thyroid hormone increases cardiac output and cardiac performance. It also induces relaxation of the vascular smooth muscle and increases endothelial function by increasing nitric oxide synthase signaling complex. Free T3 was seen to be a strong and independent predictor of death in cardiac disease as well as congestive heart failure.
Low Growth Hormone
Patients with growth hormone deficiency have impaired cardiac performance, increased peripheral vascular resistance, and reduced exercise capacity. Heart failure rates are increased, and interestingly, there was low growth hormone levels found in heart failure patients. Growth hormone also has a positive effect on the endothelium and nitric oxide, which is a vasodilator.
SUMMARY:
Atherosclerosis is a serious threat to the health and its progression has related to increased risk of heart attack, stroke, atrial fibrillation, dementia and many others. Since it may begin as early as childhood, it is vital to combat this disease early and aggressively. Comprehensive blood testing, genetic markers, as well as cardiologic evaluation is important to institute a personalized, targeted treatment regimen that can be used to improve cardiovascular health.