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DHEA

May 2015

By Andrew Levine

Reduces Cardiovascular Risks And Promotes Healthy Longevity

Thirty-four years ago, Life Extension® began informing members about a broad-spectrum anti-aging hormone that was largely unknown in the medical community. Since then, hundreds of studies have helped validate what we knew all along—that this might be an essential life-extending supplement for aging individuals.

We’re talking about the hormone DHEA.

DHEA administration has been shown to alleviate many age-related conditions—and may slow the aging process itself.1

One of the significant ways that DHEA facilitates healthy aging is through its impact on improving cardiovascular health.

New studies have shown that DHEA mounts a triple attack against three of the most prominent risk factors for cardiovascular disease: atherosclerosis, endothelial dysfunction, and metabolic syndrome.

By the time you reach the age of 70, your DHEA levels are likely to be 75 to 80% lower than when you were at your peak.2-5 The effects can be devastating.

Many scientific observations suggest that falling levels of DHEA play a role in creating many “symptoms” of aging that we see as people grow older.6,7 Large-scale studies show a correlation between low DHEA levels and increased risk of death in older men. One study found that men with the lowest DHEA levels were 67% more likely to die from a heart attack and 54% more likely to die from any cause.6,8

The good news is that just two weeks of low-cost DHEA supplementation can restore age-depleted DHEA levels to those of younger adults, with effects that reverberate throughout the body.9

What you need to know
DHEA Fights Cardiovascular Disease

DHEA Fights Cardiovascular Disease

  • Declining DHEA naturally occurs with age, but studies show that lower levels are associated with significantly increased risks of cardiovascular disease and death.
  • Restoring DHEA to more youthful levels through supplementation can reduce the impact of major cardiovascular risk factors, including atherosclerosis, endothelial dysfunction, and metabolic syndrome.
  • People who supplement with DHEA lose weight, improve their blood lipid profiles, and increase their insulin sensitivity, thereby reducing their cardiovascular risk across multiple parameters.
  • DHEA has also been shown to boost the immune system and protect against bone loss.
  • It is important to undergo regular blood testing to determine your DHEA-S levels and to get started on supplements to bring your levels back up to those you had in youth.
  • A daily supplement of 15 to 50 mg of DHEA can substantially decrease your risk of cardiovascular disease.

Dangers Of Declining DHEA

Dangers Of Declining DHEA  

What is DHEA? DHEA (short for dehydroepiandrosterone) is a hormone produced mostly in the adrenal glands. DHEA is the most abundant of all the circulating steroid hormones.8,10,11

Supplementation with DHEA rapidly raises levels of DHEA in the blood.12

By the time you reach 70, your DHEA levels are likely to be 75 to 80% lower.2-5 This is not something to take lightly, as large-scale studies show a correlation between low DHEA levels and increased risk of death in older men.

One study of more than 2,600 men aged 69 to 81 demonstrated that men in the lowest 25% of DHEA levels were:6,8

  • 54% more likely to die from any cause,
  • 61% more likely to die from cardiovascular disease, and
  • 67% more likely to die from ischemic heart disease (heart attacks) specifically.

Surprisingly, the increased risk of dying was most pronounced in the younger members of this older male group (those less than 75.4 years old), whose risk of dying from cardiovascular disease was 164% greater in the low DHEA group compared to those with higher levels.6 This is a stark reminder of the importance of having DHEA blood levels checked and initiating supplements early.

Further supporting the notion that DHEA supplementation should begin early in the course of aging is a study showing that, especially among the “oldest old,” the faster DHEA levels fall, the greater the risk of having cardiovascular disease of any kind.13

A carefully designed 2010 study demonstrated that women are also vulnerable to the effects of lower DHEA levels. In that study, among women who were already at high risk for cardiovascular disease, those in the lowest one-third of DHEA levels had a significant 155% increase in the risk of dying from cardiovascular disease.14 Another study showed that women with the lowest 25% of levels of DHEA have a 41% increase in stroke risk. In addition, low DHEA-S levels in women have been found to correlate with significant increases in arterial wall thickness and reductions in blood flow.9,15

Benefits Of DHEA Supplementation

A growing body of evidence indicates that maintaining youthful DHEA levels in your blood is a good way to fend off some of the most immediate threats to your longevity, namely the cardiovascular diseases that remain leading causes of death in the United States.

According to one study, each standard deviation (about 34%) increase in DHEA levels in the blood produced an 18% decrease in the risk of having a cardiovascular event.8 This finding confirmed earlier work suggesting that higher DHEA-S levels are protective against cardiovascular disease in men, reducing the risk of dying from coronary heart disease by 37 to 55%.16

By supplementing with DHEA, you can easily get your levels back to youthful values; most people can achieve excellent levels with a daily 15 to 50 mg dose.

Let’s now examine how falling DHEA levels affect a number of the leading cardiovascular risk factors.

DHEA And Your Cardiovascular Disease Risk Factors

Three of the main risk factors that promote cardiovascular disease are atherosclerosis (“hardening of the arteries”), poor function of the lining layer of blood vessels (endothelial dysfunction), and metabolic syndrome (the combination of central obesity, poor blood sugar control, disturbed lipids, and high blood pressure). DHEA is increasingly being found to play important roles in tempering these risk factors. Let’s investigate each of them individually.

Atherosclerosis

Atherosclerosis  

Atherosclerosis is a complex process, beginning with elevated levels of blood lipids, which oxidize and lead to inflammatory changes in artery walls. This progresses to the formation of fat-laden, inflammatory plaques that narrow the artery’s interior, ultimately slowing or stopping blood flow.17 Depending on where the narrowing is, and on how critical the flow reduction, the end result can affect the heart, brain, and other body parts. In the heart, it can lead to angina (chest pain), ischemia (loss of tissue viability from lack of oxygen), or eventually, myocardial infarction (heart attack).18-20 In the brain, it can cause either a transient ischemic attack (“mini-stroke” or “pre-stroke”) or a full-blown ischemic stroke, in which whole regions of brain tissue die.21

Numerous studies have established a clear connection between low DHEA-S levels and arterial narrowing and other characteristics of arterial walls. For example, in one study on middle-aged patients undergoing a coronary angiography (a test that shows blood flow through the coronary arteries of the heart), researchers found that those who had at least one vessel with 50% or more blockage had lower DHEA-S levels than those who had less severe narrowing.22 Another study showed that low DHEA-S levels correlated with the thickness of the carotid artery (main brain artery) in men, and with decreased mean blood flow in the carotid artery in women.23

Unfortunately, having low DHEA-S levels can cancel out the benefits of certain procedures meant to reduce heart attack risk, such as arterial bypass grafting. This is a type of surgery that improves blood flow to the heart by connecting a healthy blood vessel to the blocked coronary artery and going around the blocked portion. Researchers studied patients with arterial bypass grafting and discovered that those with lowest DHEA-S levels had the fastest rate of re-narrowing (restenosis) of the grafted vessels, placing them at renewed risk of heart attacks.22

Low DHEA-S levels are also associated with the risk of atrial fibrillation, the disordered, fluttering contractions of the heart’s upper chambers that can result from atherosclerosis. The higher the levels of DHEA-S, the lower the chances of developing atrial fibrillation. A study published in the European Journal of Preventive Cardiology showed that with each standard deviation (about 34%) increase in DHEA-S, the risk of developing atrial fibrillation falls by 26%, and is nearly three times lower in people with the highest DHEA-S levels.24

The connection between low DHEA-S levels and increased risk of atherosclerosis and its dangers to longevity are clear. The question is, can supplementing with DHEA reduce the risk of atherosclerosis? Studies in both animals and humans indicate that the answer is yes.

A study in female rabbits whose ovaries had been removed (simulating menopause) showed that DHEA efficiently reduced early signs of atherosclerosis and increased beneficial nitric oxide levels.25 (Endothelial nitric oxide is a chemical signal that tells blood vessels to relax, which widens arteries to allow increased blood flow.)

In arterial lining cells in culture, DHEA administration inhibited some of the first steps in the development of atherosclerosis, such as suppressing markers of oxidation, reducing inflammatory signals, and inhibiting the adhesion molecules that make platelets and other cells stick to artery walls to form obstructive plaques.25

A compelling study of healthy older men (averaging 65.4 years old) demonstrated the value of blood testing and supplementation with DHEA for reducing cardiovascular risk.26 For two months, the men took either 50 mg of DHEA daily at bedtime or a placebo; they had their blood markers of cardiovascular risk measured before and after treatment. While the placebo-treated men had no significant changes in their risk factors, the DHEA group had numerous benefits. They experienced increased levels of testosterone and increased markers of nitric oxide production. In addition, their LDL (or “bad”) cholesterol fell significantly, as did a marker of blood clotting tendency. Together, that’s a three-way reduction in cardiovascular risk: less dangerous cholesterol to oxidize; suppler, more responsive arterial walls; and less “sticky” blood that is prone to causing clots.

Endothelial Dysfunction

Another major risk factor for cardiovascular disease is endothelial dysfunction, which is damage to the ultrathin, single layer of cells that lines blood vessels. The endothelium plays an important role in heart health because it responds to changes in blood flow and pressure. The endothelium uses nitric oxide and other molecules to signal smooth muscle in artery walls to constrict or relax in response to need.27

Damage to the endothelial layer occurs as oxidized fats begin to build up;28 endothelial dysfunction then results in poorly-responsive arterial walls, which often overgrow and thicken, further limiting their suppleness.29 Inflammatory changes within the vessel wall then rapidly contribute to further dysfunction, loss of responsiveness, and eventually to plaque formation.30

Studies are showing that DHEA can inhibit many of the threats to endothelial function that can lead to cardiovascular disease. For example, treating endothelial cells in culture with DHEA reduces the very earliest inflammatory changes by decreasing the expression of proteins that trigger inflammation.31 Additionally, DHEA treatment also increased the production of artery-relaxing nitric oxide.11,32

The impact of falling DHEA-S levels on endothelial function is especially apparent in women after menopause, when their risk for cardiovascular disease rises rapidly, eventually becoming similar to that of men.33 A study of postmenopausal women with known coronary risk factors showed that those in the highest 25% of DHEA-S levels had 80% better endothelial function (as measured by arterial dilation) than those in the lowest 25%.34

DHEA supplementation in humans can improve deteriorating endothelial function. This was clearly shown in a group of middle-aged men with elevated cholesterol who took 25 mg of DHEA per day. After eight weeks, the DHEA supplement produced a 77% increase in arterial relaxation, and by 12 weeks, the DHEA supplement produced a significant 115% improvement!35 Supplementation also resulted in significant reductions in a protein that promotes blood clotting and a 26% reduction in blood glucose levels, which are also associated with poor endothelial function.

A study of healthy postmenopausal women had very similar effects. After using 100 mg of DHEA per day for three months, they experienced improved arterial relaxation and enhanced blood flow, while reducing total cholesterol.32

How DHEA Is Measured In The Blood
How DHEA Is Measured In The Blood

DHEA and its “sulfated” form called DHEA-S are the most abundant of all the circulating steroid hormones.8,10,11 Both DHEA and DHEA-S can be measured in the blood; however, since DHEA-S is a more stable form and found in significantly higher levels than DHEA, the DHEA-S form is what is usually tested in the blood (serum) to evaluate the body’s overall DHEA status.9 Supplementation with DHEA raises serum DHEA-S levels.12

 

Metabolic Syndrome

Metabolic syndrome is a major threat to cardiovascular health, an accelerator of aging, and a cause of premature death. The syndrome consists of central obesity (excess belly fat), poor blood sugar control, abnormal lipid levels, and high blood pressure.36 The risks of dying a cardiovascular death are increased by up to 200% in people with metabolic syndrome compared to those without.37

As DHEA declines, the rate of metabolic syndrome rises, which is hardly surprising, since DHEA regulates most of the processes that influence metabolic health.38-41

Fortunately, as with atherosclerosis and endothelial dysfunction, supplementing with DHEA has numerous positive benefits on metabolic syndrome.

Laboratory studies have shown that DHEA administration reduces abdominal fat and insulin resistance, two of the major features of metabolic syndrome.42 Human studies are even more impressive, with a large number of studies consistently showing that in both men and postmenopausal women, taking 15 to 50 mg per day of DHEA leads to significant beneficial changes in almost all metabolic syndrome parameters, including:

Metabolic Syndrome  
  • Decreases in visceral (belly) fat,42
  • Decreases in subcutaneous (under the skin) fat,42
  • Increases in insulin sensitivity of up to 30%,43
  • Decreases in overall insulin exposure42 (elevated insulin is associated with an increased risk of developing heart disease, diabetes, cancer, and excessive inflammation),44-48
  • Increases in protective HDL levels of nearly 12%,43
  • Decreases in dangerous LDL cholesterol of up to 11%,43
  • Decrease of almost 20% in plasma triglycerides,43
  • Increases in levels of insulin-like growth factor-1 (IGF-1), a molecule that is vital to controlling blood sugar and other metabolic parameters,49
  • Dramatic improvement in physical and psychological well-being by 67% in men and 84% in women,50
  • Beneficial increases in estrogen levels, even without specific hormone replacement therapy for menopause;49 those changes may further help to protect postmenopausal women from the elevated cardiovascular disease risks of menopause, and
  • No significant side effects.51

Additionally, specifically in obese women (both pre- and postmenopausal), 100 mg per day of DHEA supplementation decreased plasma-saturated fatty acids and increased levels of protective fatty acids such as omega-3 and omega-6.52 Another study by the same group showed that 100 mg per day of DHEA also led to significant weight loss, improved waist circumference, improved blood pressure, a marked decrease in blood glucose levels, and a significant reduction in the total metabolic syndrome score in postmenopausal women.53

DHEA Supports Immunity And Improves Bone Health

In addition to its ability to promote cardiovascular health and prevent premature death, DHEA supplements are also showing promise in other areas that contribute to decreased longevity and diminished quality of life in older adults. Two of the main areas are immunity and bone health.

Immune Support

The immune system wanes with age, resulting in increased vulnerability to infections and cancer. This is called immune senescence. DHEA is increasingly recognized as a means of improving the immune response in older adults.54,55

One study found that supplementing with 50 mg per day of DHEA for 20 weeks boosted the number and function of a broad array of immune system cells and signaling molecules that are generally diminished with aging.12 This translates to improved immunity against bacteria, viruses, and fungal infections, as well as better surveillance to catch and destroy incipient cancer cells before they erupt into full-blown malignancies.

DHEA has been shown to help boost the body’s response to the flu vaccine. A study published in the Journal of the American Geriatrics Society demonstrated that a one-time subcutaneous injection of 7.5 mg of DHEA markedly boosted antibody responses to the flu vaccine.56 This is especially critical in older adults since they have been found to respond more poorly to vaccines than younger people, which increases the risks for preventable infections.57

Why You Need Regular DHEA Blood Testing

DHEA levels in your blood begin falling in early middle age; by the time you reach 70, your levels are likely to be 75 to 80% lower than when you were at your peak.2-5 Fortunately, you can get your levels back to youthful values by supplementing with DHEA; most people can achieve excellent levels with a daily 15 to 50 mg dose.64,65

But because of the natural biological variability in DHEA levels, it is important that you check your blood levels periodically for two reasons. First, if your level is low, you’ll need to increase your supplement dose to bring the level closer to ideal. Second, you may find, after a few weeks of supplementation, that you are at or near your optimum level. This could save you money by allowing you to slightly lower your dose.

Standard testing for DHEA involves measuring the circulating levels of DHEA-S, the sulfated form of the hormone that predominates in the blood. These levels accurately reflect circulating levels of DHEA itself and are more stable as an indication of true DHEA values.

DHEA is included in the popular Male and Female Blood Test Panels that can be ordered by calling 1-800-208-3444 (24 hours a day). These tests are heavily discounted through June 1, 2015.)

What Levels Should You Aim For?

Remember, there’s a difference between “normal” levels and those that are considered ideal for optimum health. “Normal” levels for men range from 20.8 to 530.5 micrograms/dL, and for women, 13.9 to 433.2 micrograms/dL. But “normal” levels are simply averages for populations not known to have any specific disease, hence the very wide range.

You should aim for levels established as “ideal” for restoring your DHEA function to youthful values. For women, an ideal DHEA-S level is 275 to 400 micrograms/dL, and in men, 350 to 500 micrograms/dL. People who don’t supplement with DHEA typically have levels below 200 micrograms/dL, and in older adults that level can drop to less than 100.4

Because of DHEA’s excellent safety record and the likelihood that your levels are low, you may choose to start supplementing at 25 mg per day, then get your blood tested in four weeks’ time, adjusting your dose as needed. Or, you may choose to test first, then add the supplement once you’ve seen your levels.

Either way, be sure to keep a close eye on your levels so that you can regularly adjust your dose to stay in the range that is ideal for promoting your cardiovascular (and general) health.

Bone Health

Osteoporosis poses a major threat to both men and women as they age. Weaker bones means higher risk for serious fractures,58 including the dreaded hip fractures that put so many older adults into hospitals, where they are at risk for all kinds of life-shortening complications.59,60

DHEA appears to contribute to stronger bones in both men and women, though studies indicate that men need to take twice the amount as women in order to achieve benefits. One study found that 50 mg of DHEA can improve bone mineral density and reduce bone resorption in women, but not in men.61 However, another study found that elderly men experienced significantly improved bone mineral density in lumbar vertebrae and hip bones with a 100 mg dose of DHEA-S daily.62

In older women with significant frailty, a daily 50 mg dose of DHEA also improved muscle strength and physical function, when accompanied by mild physical exercise.63 These changes may help to reduce fracture risk simply by reducing the risk of a serious fall in the first place.

DHEA Usage And Safety Precautions
DHEA Usage And Safety Precautions

DHEA is a very safe supplement,66 but certain precautions for both men and women should be observed.

For Men

A review of the published literature provides persuasive arguments that DHEA does not have an effect on prostate cancer risk or indolent prostate cancer cells. Studies in fact show lower DHEA levels in newly diagnosed prostate cancer patients compared to age-matched controls. Men on aggressive hormone ablation therapy may want to discontinue DHEA during the time they are on this therapy.67-70

You should know your prostate specific antigen (PSA) level before embarking on a DHEA supplementation regimen. If you suspect or have been diagnosed with prostate cancer, consult your physician before using DHEA. Please note the following:

  • A rising PSA and/or a positive digital rectal exam may suggest early prostate cancer.
  • Have a PSA level and a digital rectal exam done before starting DHEA to rule out existing prostate disease.
  • Then have a physician check your PSA and DHEA-S serum levels every six to 12 months thereafter.
  • Men should also periodically check their blood levels for free testosterone and estrogen.

While taking DHEA, men should also consider taking the following nutrients, which may enhance DHEA’s effectiveness when taken daily:

  • 5,000-10,000 IU of vitamin D3
  • 200 mg of gamma E tocopherol
  • 10-40 mg of lycopene extract
  • 3-10 mg of boron
  • 400 mg of supplement containing a standardized broccoli extract

For Women

Because DHEA supplementation can influence estrogen and testosterone levels in women, women should consider getting blood tests for those hormones at the same time that they obtain a DHEA test.

If you have been diagnosed with an estrogen-dependent cancer, you should consult with your physician before beginning DHEA restoration therapy.

When taking DHEA, women should also consider taking the following nutrients, which may enhance DHEA’s effectiveness when taken daily:

  • 400 IU of vitamin E (D-alpha tocopheryl succinate)
  • 400 mg of supplement containing a standardized broccoli extract
  • 80-160 mg of indole-3-carbinol
  • 5,000-10,000 IU of vitamin D3
  • 200 mg of gamma E tocopherol

Summary

DHEA is a potent regulator of many of the processes that, uncorrected, raise your risk of a heart attack, stroke, or other degenerative catastrophes.

Studies now show that people with cardiovascular diseases have significantly lower levels of circulating DHEA and people with low DHEA levels die younger than those with more youthful levels. The good news is that regular supplementation with modest doses (15 to 50 mg per day) of DHEA can significantly reduce the risk of three of the main risk factors for cardiovascular disease: atherosclerosis, endothelial dysfunction, and metabolic syndrome.

In addition, emerging science suggests supplementing with DHEA can help prevent declining immune system function with age and can improve bone health.

It’s important to have one’s blood tested after initiating DHEA supplementation to ensure the proper dose is used. Some people need only 15 mg a day while others may require 50 mg a day and higher. The reason older people should start DHEA before having their blood drawn for testing is that almost everyone over age 40 has less-than-optimal DHEA levels.

For those not already supplementing, we suggest they start at a dose of 25 mg a day and then have their blood drawn two to three weeks later. The results from this blood test can help determine the optimal individual dose.

A test for DHEA is included in the comprehensive Male and Female Blood Test Panels that most Foundation members order now because they are available at the year’s lowest prices.

DHEA supplements are remarkably inexpensive, making it affordable to include DHEA in one’s healthy longevity program.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

  1. Stomati M, Monteleone P, Casarosa E, et al. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol Endocrinol. 2000 Oct;14(5):342-63.
  2. Orentreich N, Brind JL, Vogelman JH, Andres R, Baldwin H. Long-term longitudinal measurements of plasma dehydroepiandrosterone sulfate in normal men. J Clin Endocrinol Metab. 1992 Oct;7s5(4):1002-4.
  3. Labrie F, Bélanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab. 1997 Aug;82(8):2396-402.
  4. Orentreich N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984 Sep;59(3):551-5.
  5. Villareal DT, Holloszy JO. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1003-8. Epub 2006 Jun 20.
  6. Ohlsson C, Labrie F, Barrett-Connor E, et al. Low serum levels of dehydroepiandrosterone sulfate predict all-cause and cardiovascular mortality in elderly Swedish men. J Clin Endocrinol Metab. 2010 Sep;95(9):4406-14.
  7. Abraham PA, Kazman JB, Zeno SA, Poth M, Deuster PA. Age-related decline in salivary dehydroepiandrosterone sulfate and associated health risks among African Americans. Ethn Dis. 2013 Spring;23(2):149-54.
  8. Tivesten A, Vandenput L, Carlzon D, et al. Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men. J Am Coll Cardiol. 2014 Oct 28;64(17):1801-10.
  9. Jimenez MC, Sun Q, Schurks M, et al. Low dehydroepiandrosterone sulfate is associated with increased risk of ischemic stroke among women. Stroke. 2013 Jul;44(7):1784-9.
  10. Savineau JP, Marthan R, Dumas de la Roque E. Role of DHEA in cardiovascular diseases. Biochem Pharmacol. 2013 Mar 15;85(6):718-26.
  11. Perrini S, Laviola L, Natalicchio A, Giorgino F. Associated hormonal declines in aging: DHEAS. J Endocrinol Invest. 2005;28(3 Suppl):85-93.
  12. Khorram O, Vu L, Yen SS. Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men. J Gerontol A Biol Sci Med Sci. 1997 Jan;52(1):M1-7.
  13. Sanders JL, Boudreau RM, Cappola AR, et al. Cardiovascular disease is associated with greater incident dehydroepiandrosterone sulfate decline in the oldest old: the cardiovascular health study all stars study. J Am Geriatr Soc. 2010 Mar;58(3):421-6.
  14. Shufelt C, Bretsky P, Almeida CM, et al. DHEA-S levels and cardiovascular disease mortality in postmenopausal women: results from the National Institutes of Health--National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women’s Ischemia Syndrome Evaluation (WISE). J Clin Endocrinol Metab. 2010 Nov;95(11):4985-92.
  15. Kanazawa I, Yamaguchi T, Yamamoto M, et al. Serum DHEA-S level is associated with the presence of atherosclerosis in postmenopausal women with type 2 diabetes mellitus. Endocr J. 2008 Aug;55(4):667-75.
  16. Khaw KT. Dehydroepiandrosterone, dehydroepiandrosterone sulphate and cardiovascular disease. J Endocrinol. 1996 Sep;150 Suppl:S149-53.
  17. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic mechanisms-oxidation, inflammation, and genetics. Circulation. 1995 May 1;91(9):2488-96.
  18. Slijkhuis W, Mali W, Appelman Y. A historical perspective towards a non-invasive treatment for patients with atherosclerosis. Neth Heart J. 2009 Apr;17(4):140-4.
  19. Cassar A, Holmes DR, et al. Chronic coronary artery disease: Diagnosis and management. Mayo Clin Proc. 2009 Dec; 84(12): 1130–46.
  20. Alie N, Eldib M, Fayad ZA, Mani V. Inflammation, atherosclerosis, and coronary artery disease: PET/CT for the evaluation of atherosclerosis and inflammation. Clin Med Insights Cardiol. 2015 Jan 7;8(Suppl 3):13-21.
  21. Adams HP Jr. Secondary prevention of atherothrombotic events after ischemic stroke. Mayo Clin Proc. 2009;84(1):43-51.
  22. Herrington DM. Dehydroepiandrosterone and coronary atherosclerosis. Ann N Y Acad Sci. 1995 Dec 29;774:271-80.
  23. Yoshida S, Aihara K, Azuma H, et al. Dehydroepiandrosterone sulfate is inversely associated with sex-dependent diverse carotid atherosclerosis regardless of endothelial function. Atherosclerosis. 2010 Sep;212(1):310-5.
  24. Krijthe BP, de Jong FH, Hofman A, et al. Dehydroepiandrosterone sulfate levels and risk of atrial fibrillation: the Rotterdam Study. Eur J Prev Cardiol. 2014 Mar;21(3):291-8.
  25. Wang L, Hao Q, Wang YD, Wang WJ, Li DJ. Protective effects of dehydroepiandrosterone on atherosclerosis in ovariectomized rabbits via alleviating inflammatory injury in endothelial cells. Atherosclerosis. 2011 Jan;214(1):47-57.
  26. Martina V, Benso A, Gigliardi VR, et al. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects. Clin Endocrinol (Oxf). 2006 Mar;64(3):260-4.
  27. Moncada S, Higgs EA. Nitric oxide and the vascular endothelium. Handb Exp Pharmacol. 2006;(176 Pt 1):213-54.
  28. Yang H, Mohamed AS, Zhou SH. Oxidized low density lipoprotein, stem cells, and atherosclerosis. Lipids Health Dis. 2012 Jul 2;11:85.
  29. Tao J, Jin YF, Yang Z, Wang LC, Gao XR, Lui L, Ma H. Reduced arterial elasticity is associated with endothelial dysfunction in persons of advancing age: comparative study of noninvasive pulse wave analysis and laser Doppler blood flow measurement. Am J Hypertens. 2004 Aug;17(8):654-9.
  30. Donato AJ1, Morgan RG2, Walker AE3, Lesniewski LA4. Cellular and molecular biology of aging endothelial cells. J Mol Cell Cardiol. 2015 Feb 2. pii: S0022-2828(15)00034-6.
  31. Li Y, Xia Z, Wang M. Dehydroepiandrosterone inhibits CD40/CD40L expression on human umbilical vein endothelial cells induced by interferon gamma. Int Immunopharmacol. 2009 Feb;9(2):168-72.
  32. Williams MR, Dawood T, Ling S, et al. Dehydroepiandrosterone increases endothelial cell proliferation in vitro and improves endothelial function in vivo by mechanisms independent of androgen and estrogen receptors. J Clin Endocrinol Metab. 2004 Sep;89(9):4708-15.
  33. Mascarenhas-Melo F, Sereno J, Teixeira-Lemos E, et al. Markers of increased cardiovascular risk in postmenopausal women: focus on oxidized-LDL and HDL subpopulations. Dis Markers. 2013;35(2):85-96.
  34. Akishita M, Hashimoto M, Ohike Y, et al. Association of plasma dehydroepiandrosterone-sulfate levels with endothelial function in postmenopausal women with coronary risk factors. Hypertens Res. 2008 Jan;31(1):69-74.
  35. Kawano H, Yasue H, Kitagawa A, et al. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab. 2003 Jul;88(7):3190-5.
  36. Hofmann SM, Tschöp MH. Dietary sugars: a fat difference. J Clin Invest. 2009 May;119(5):1089-92.
  37. Moe B, Mork PJ, Holtermann A, Nilsen TI. Occupational physical activity, metabolic syndrome and risk of death from all causes and cardiovascular disease in the HUNT 2 cohort study. Occup Environ Med. 2013 Feb;70(2):86-90.
  38. Richards RJ, Porter JR, Svec F. Serum leptin, lipids, free fatty acids, and fat pads in long-term dehydroepiandrosterone-treated Zucker rats. Proc Soc Exp Biol Med. 2000 Mar;223(3):258-62.
  39. Coleman DL. Therapeutic effects of dehydroepiandrosterone (DHEA) and its metabolites in obese-hyperglycemic mutant mice. Prog Clin Biol Res. 1988;265:161-75.
  40. Bonnet S, Dumas-de-La-Roque E, Bégueret H, et al. Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension. Proc Natl Acad Sci USA. 2003 Aug 5;100(16):9488-93.
  41. Suzuki M, Kanazawa A, Hasegawa M, Hattori Y, Harano Y. A close association between insulin resistance and dehydroepiandrosterone sulfate in subjects with essential hypertension. Endocr J. 1999 Aug;46(4):521-8.
  42. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. Jama. 2004 Nov 10;292(18):2243-8.
  43. Lasco A, Frisina N, Morabito N, et al. Metabolic effects of dehydroepiandrosterone replacement therapy in postmenopausal women. Eur J Endocrinol. 2001 Oct;145(4):457-61.
  44. Meigs JB, Larson MG, D’Agostino RB, et al. Coronary artery calcification in type 2 diabetes and insulin resistance: the Framingham offspring study. Diabetes Care. 2002 Aug;25(8):1313-9.
  45. Park SK, Jung JY, Choi WJ, et al. Elevated fasting serum insulin level predicts future development of hypertension. Int J Cardiol. 2014 Mar 15;172(2):450-5.
  46. Pradhan AD, Cook NR, Buring JE, Manson JE, Ridker PM. C-reactive protein is independently associated with fasting insulin in nondiabetic women. Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):650-5.
  47. Pradhan AD, Manson JE, Meigs JB, et al. Insulin, proinsulin, proinsulin:insulin ratio, and the risk of developing type 2 diabetes mellitus in women. Am J Med. 2003 Apr 15;114(6):438-44.
  48. Senechal M, Lemieux I, Beucler I, et al. Features of the metabolic syndrome of “hypertriglyceridemic waist” and transplant coronary artery disease. J Heart Lung Transplant. 2005 Jul;24(7):819-26.
  49. Genazzani AD, Stomati M, Strucchi C, Puccetti S, Luisi S, Genazzani AR. Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women. Fertil Steril. 2001 Aug;76(2):241-8.
  50. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab. 1994 Jun;78(6):1360-7.
  51. Diamond P, Cusan L, Gomez JL, Belanger A, Labrie F. Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women. J Endocrinol. 1996 Sep;150 Suppl:S43-50.
  52. Gomez-Santos C, Larque E, Granero E, Hernandez-Morante JJ, Garaulet M. Dehydroepiandrosterone-sulphate replacement improves the human plasma fatty acid profile in plasma of obese women. Steroids. 2011 Dec 11;76(13):1425-32.
  53. Gomez-Santos C, Hernandez-Morante JJ, Tebar FJ, Granero E, Garaulet M. Differential effect of oral dehydroepiandrosterone-sulphate on metabolic syndrome features in pre- and postmenopausal obese women. Clin Endocrinol (Oxf). 2012 Oct;77(4):548-54.
  54. Buford TW, Willoughby DS. Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Appl Physiol Nutr Metab. 2008 Jun;33(3):429-33.
  55. Hazeldine J, Arlt W, Lord JM. Dehydroepiandrosterone as a regulator of immune cell function. J Steroid Biochem Mol Biol. 2010 May 31;120(2-3):127-36.
  56. Degelau J, Guay D, Hallgren H. The effect of DHEAS on influenza vaccination in aging adults. J Am Geriatr Soc. 1997 Jun;45(6):747-51.
  57. Lambert ND, Ovsyannikova IG, Pankratz VS, Jacobson RM, Poland GA. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 2012 Aug;11(8):985-94.
  58. Hochberg MC. Racial differences in bone strength. Trans Am Clin Climatol Assoc. 2007;118:305-15.
  59. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013 Jan;24(1):23-57.
  60. Lee C, Porter K. The prehospital management of pelvic fractures. Emerg Med J. 2007 Feb;24(2):130-3.
  61. Von Muhlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int. 2008 May;19(5): 699-707.
  62. Sun Y, Mao M, Sun L, Feng Y, Yang J, Shen P. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J (Engl). 2002 Mar;115(3):402-4.
  63. Kenny AM, Boxer RS, Kleppinger A, Brindisi J, Feinn R, Burleson JA. Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women. J Am Geriatr Soc. 2010 Sep;58(9):1707-14. Hi Robert,
  64. Legrain S, Massien C, Lahlou N, et al. Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J Clin Endocrinol Metab. 2000 Sep;85(9):3208-17.
  65. Bowers LD. Oral dehydroepiandrosterone supplementation can increase the testosterone/epitestosterone ratio. Clin Chem. 1999 Feb;45(2):295-7.
  66. Samaras N, Papadopoulou MA, Samaras D, Ongaro F. Off-label use of hormones as an antiaging strategy: a review. Clin Interv
    Aging
    . 2014 Jul 23;9:1175-86.
  67. Belanger A, Candas B, Dupont A, et al. Changes in serum concentrations of conjugated and unconjugated steroids in 40 to 80 year-old men. J Clin Endocrinol Metab. 1994 Oct;79(4):1086-90.
  68. Sah C, Aridogan I, Izol V, et al. Effects of long-term administration of the antiaging hormone dehydroepiandrosterone sulfate on rat prostates and testes as androgen-dependent organs. Korean J Urol. 2013 Mar;54(3):199-203.
  69. Stahl F, Schnorr D, Pilz C, Dorner G. Dehydroepiandrosterone levels in patients with prostatic cancer, heart diseases and surgery under stress. Exp Clin Endocrinol. 1992;99:68-70.
  70. Comstock GW, Gordon GB, Hsing AW. The Relationship of Serum Dehydroepiandrosterone and its Sulfate to Subsequent Cancer of the Prostate. Cancer Epidemiol Biomarkers Prev. 1993;2(3):219-21.