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Life Extension Magazine

LE Magazine August 2005
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Women and Coronary Heart Disease

A Novel Approach to Coronary Heart Disease Prevention By Dr. Sergey Dzugan

Coronary heart disease (CHD) is the leading cause of death in the Western world. Although physicians and patients tend to think of CHD as a man’s disease, it is the leading cause of death among women in the US. Because of this misconception, physicians may fail to look for this condition in women or fail to recognize its warning signs, which may differ among women and men.

Numerous risk factors contribute to CHD risk, including non-modifiable factors such as age and family history, and modifiable risk factors such as cholesterol level, homocysteine level, and high blood pressure. Because the incidence of CHD in women increases markedly following menopause (when levels of ovarian hormones drop dramatically), researchers have speculated that female hormones may play a cardioprotective role. Recent studies such as the Women’s Health Initiative (WHI), however, have failed to demonstrate a relationship between conventional hormone replacement therapy (HRT) and protection from CHD. As a result of such studies, many women and physicians have avoided HRT, fearing that it may increase CHD risk.

We believe that trials such as the WHI failed to demonstrate a cardioprotective effect of female hormones for several reasons: namely, that these trials used forms of hormones that are not biochemically identical to those naturally found in women; that the trials used a “one-size-fits-all” dosing strategy; and that the trials did not cycle hormones to mimic the normal menstrual cycle. Our clinical experience suggests that a more refined form of HRT, which we call hormonorestorative therapy, or hormonorestoration, may indeed offer cardioprotection by helping minimize several CHD risk factors.

HOW CORONARY HEART DISEASE DEVELOPS

Coronary arteries are blood vessels that wrap around the heart and supply the heart muscle with oxygen and nutrients.

Coronary heart disease (CHD) occurs when the artery walls become hardened and narrowed due to buildup of fatty deposits called plaque. As plaque narrows the coronary arteries, blood flow to the heart muscle is gradually decreased, diminishing the heart’s oxygen and nutrient supply.

Over time, CHD can weaken the heart muscle and foster the development of congestive heart failure, a condition in which the heart cannot effectively pump blood to the rest of the body.

Introduction

In this article, we examine the principles of hormonorestorative therapy and two case histories in which individualized hormonorestoration helped reduce multiple cardiovascular risk factors in women. Additionally, we review CHD risk factors, symptoms, and diagnosis, along with conventional and integrative strategies for heart disease prevention and treatment. We propose that an individualized strategy of hormonorestorative therapy represents a novel yet powerful approach to reducing CHD risk in women.

CHD is the most common type of heart disease. According to the American Heart Association, CHD kills 241,622 women in the US each year, compared to 67,542 lives lost to lung cancer and 41,514 to breast cancer. Thirty-eight percent of US women (compared to 25% of men) die within one year of suffering a heart attack.1 CHD affects women of all racial and ethnic groups, though African-American women are more likely to die of CHD than are Caucasian women.1

Age is an important risk factor for CHD. Women tend to develop CHD later in life than men do, experiencing a greater risk after their reproductive years.2 After menopause, women have heart problems as often as men do. It is thought that naturally occurring female hormones may help protect a woman’s heart from CHD before menopause. As their life expectancy continues to increase, women spend more time in the postmenopausal phase of life, which may increase CHD risk. CHD is fast becoming a major cause of morbidity and mortality in aging women, particularly with rapid growth in the number of women aged 65 and over.

The HRT Controversy

It is a well-known fact that CHD is uncommon in women before the age of 40. The biggest change in a woman’s body at this time is the declining production of most steroid hormones. This may lead to a loss of hormonal cardioprotective effects, because the cardiovascular system is controlled by multiple endocrine signals.3 Until recently, it was generally believed that the decreased incidence of CHD in women before menopause was mediated by a protective effect of estrogen on the coronary arteries, achieved by modulating levels of serum cholesterol.4 However, other research suggests that estrogen-induced improvements in serum cholesterol account for only one third of the observed clinical benefits of estrogen.4-7 It was hypothesized that an atheroprotective effect of estrogen may be mediated by this hormone’s direct effect on vascular smooth muscle cells.8 In fact, the data show that estrogen can increase dilation of arteries and inhibit the response of blood vessels to injury and the development of atherosclerosis.4

Few studies have explored the relationship between androgen levels and CHD in women. The idea that DHEA protects against atherosclerosis was proposed by Kask in 1959.9 Some data show that serum dehydroepiandrosterone sulfate (DHEA-S) and androgen levels decline with age, and that levels in the normal physiological range are correlated with lower risk of carotid artery atherosclerosis.10 There is growing support for a possible benefit of DHEA supplementation in preventing cardiovascular events in women, predominantly through an estrogenic effect.11-13 Testosterone can regulate vascular physiology directly through stimulation of androgen receptors and inhibition of plaque formation, and indirectly after conversion to estradiol.14 Nevertheless, evidence concerning the efficacy of DHEA and testosterone in protecting the cardiovascular system remains inconclusive and warrants further study.

Comparison of Triest and
Premarin® with Naturally
Occurring Estrogens in Women

Estrogens in women:

In women, estrogens normally exist in approximately the following ratio:
Estriol 60-80%
Estradiol 10-20%
Estrone 10-20%

Triest:

The composition of Triest can vary depending on the prescribing doctor’s recommendations. The most common Triest formulation is:
Estriol 80%
Estradiol 10%
Estrone 10%

Premarin®:

Conjugated equine estrogens,
consisting of estrone sulfate and equine estrogens.

Conventional HRT has been the subject of much bad publicity in recent years, which has scared many women and their doctors away from the use of all types of hormones. Since hormones are critical for the normal function and well-being of the human body, this represents a catastrophic health disaster. While many of us have heard that estrogen is dangerous, there must be something more to the story, since all men, women, and children naturally have estrogens in their bodies. Blanket statements that estrogen is harmful overlook the larger picture.

In fact, the body produces several estrogens, of which the three most important are estriol, estradiol, and estrone. Estradiol and estrone are generally considered to be procarcinogenic (able to stimulate cancerous changes).15 Estriol has been touted as a much safer estrogen and, in fact, may actually decrease the risk of neoplastic changes.16 Nevertheless, it is important to note that estradiol and estrone play important roles in the body, as all hormones do, and may be dangerous only in cases of hormonal imbalance. Estrogens do not exist in isolation but instead counteract each other. They help determine female physical appearance, can improve skin and bone conditions, may help with lubrication of mucous membranes, allow ovulation, and support the central nervous system, among other actions.16

According to the critics, estrogen is not the only “bad” hormone. Progesterone also has recently come under fire in the medical community. It should be noted, however, that many of the reported ill effects ascribed to progesterone arose from synthetic progesterone analogs called progestins. Unlike progesterone, progestins are not biochemically identical to the compounds naturally found in women’s bodies. These synthetic progestins can produce side effects that generally do not occur with bioidentical progesterone.17 In fact, progesterone can be helpful for both men and women in balancing and offsetting the strong effects of estrogen.

Until a few years ago, hormone replacement therapy was considered a first-line treatment for preventing CHD in women.18 After publication of the Heart and Estrogen/Progestin Replacement Follow-up (HERS II)19 and WHI20 studies, researchers claimed that HRT not only provided no cardioprotective benefit for women, but in fact did just the opposite, increasing CHD risk. Examination of the design of these studies, however, reveals that they did not use hormone forms that are bioidentical to those naturally found in the human body. Synthetic HRT typically uses 0.625 mg/d of conjugated equine estrogens and 2.5 mg/d of medroxyprogesterone acetate (progestin). The human body does not produce these hormones (Premarin® or Provera®) and thus has no deficiency of them. However, our bodies can be deficient of naturally occurring hormones such as total estrogen (which includes estriol, estrone, and estradiol) and progesterone, among others.

RISK FACTORS FOR CORONARY HEART DISEASE

Risk factors for coronary heart disease can be classified as non-modifiable and modifiable.

Non-modifiable risk factors for CHD include:

• age
• gender
• ethnicity
• family history of CHD (having close relatives with heart disease).

Modifiable risk factors for CHD include:

• high cholesterol
• high homocysteine
• high blood pressure
• diabetes
• metabolic syndrome
• high C-reactive protein (CRP)
• being overweight or obese
• smoking
• sedentary lifestyle
• high stress level.

In recent years, the constellation of hypertension (elevated blood pressure), dyslipidemia (lipid disorder), insulin resistance/glucose intolerance, obesity, and a proinflammatory state (recognized clinically by elevated CRP) has been defined as metabolic syndrome or Syndrome X. About 47 million people in the US have metabolic syndrome21 and thus are at increased risk for CHD.22

High cholesterol and high blood pressure, two other risk factors for CHD, are very common among aging women. Approximately 40% of women over 55 have elevated serum cholesterol and approximately 52% of women over 45 have elevated blood pressure.23

Multiple epidemiological studies have shown that elevated plasma homocysteine is an independent risk factor for CHD.24,25 A 5-mumol/L increase in homocysteine elevates CHD risk as much as a 0.5-mmol/L (20 mg/dL) increase in cholesterol.26

Diabetes is a prominent cardiovascular risk factor in women, increasing CHD risk three to seven times, compared with a two to three times greater risk in men.9 In addition, mild elevation of baseline levels of high-sensitivity CRP is associated with higher long-term risk for CHD.27,28

Smoking and obesity are two other risk factors for CHD in women.29,30 Smoking may be an especially important contributor to heart disease in women, as smoking rates are declining less in women than in men.23 Obesity is associated with coronary artery calcification, a marker of the presence and extent of subclinical and clinical coronary atherosclerosis.31

Sedentary lifestyle and physical inactivity also elevate cardiovascular risk in women. Approximately 25% of women reportedly engage in no regular sustained physical activity.23 In addition, strong evidence supports an independent causal association between psychosocial risk factors such as depression, social isolation, and lack of quality social support and the causes and prognosis of CHD.32

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