Estradiol and Heart Disease

Estradiol Studies

Imagine if a pharmaceutical company created a drug that cut your risk of heart disease, colon cancer and Alzheimer’s disease by almost 40%, decreased osteoporosis, gave you healthier teeth and skin, and made you feel great! That drug would fly off the shelves: an instant blockbuster. Surprisingly, that drug already exists, it’s FDA-approved, and best of all it’s not patented.

It’s inexpensive, bio-identical Estrogen.

Heart disease is the #1 killer of women, regardless of race or ethnicity.

In 2007, one out of every four women who died in America was killed by heart disease! That’s 306,000 women, in contrast to the 41,000 that died of breast cancer. As emotional as our response to breast cancer is, we should be far more concerned about cardiovascular disease (Some doctors have pointed out that we should be sponsoring walks with red ribbons for all the women that die every year from stroke and heart disease). Estrogen is one of the most effective weapons we have against heart disease! This section provides an overview of key research in this area.

Obstetrics and Gynecology (1996)

Over 90% of women will die from cardiovascular disease, which estrogen can prevent. Over 40 years of study have well documented the cardiovascular protective effects of estrogen.

Ettinger, B., D. Friedman, G., Bush, T., & Quesenberry, C. P. (1996). Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstetrics & Gynecology, 87(1), 6-12.

New England Journal of Medicine (2000)

“Estrogen therapy alters the biology of the inner vessels (of the heart). Hormone replacement therapy protects through vasodilation, anti inflammatory and anti-proliferative effects, providing significant coronary artery benefits.”

Nabel, E. G. (2000). Coronary heart disease in women — an ounce of prevention. New England Journal of Medicine, 343(8), 572-574.

Journal of the American Medical Association (1995)

The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial: PEPI was a 3-year, multicenter, randomized, double-blind, placebo-controlled trial performed with 875 healthy postmenopausal women aged 45 to 64.

CONCLUSIONS: Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels. Estrogen with natural bio-identical progesterone has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia.

Miller, V. T., LaRosa, J., Barnabei, V., Kessler, C., Levin, G., Smith-Roth, A., . . . Kessler, G. (1995). Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA, 273(3), 199-208.

(In other words, when they used natural bio-identical progesterone instead of altered, synthetic MPA (Provera), the result was a better effects on lipids and also no increased risk of uterine cancer.)

Maturitas (1998)

Many epidemiological studies show that women who use estrogen therapy after menopause have significantly lower rates of heart disease than postmenopausal women who do not take estrogen. This review assessed the impact of estrogen use among women with particularly high cardiovascular risk. Seven studies of estrogen therapy in women with established coronary heart disease (such as coronary stenosis and prior heart attack) were reviewed:

These studies all find fewer recurrent cardiovascular events and improved survival in the estrogen group when compared to the non-estrogen group. Analysis of the effect of estrogen within different risk categories in the 16-year follow up of the Nurses’ Health Study confirms that the protective effect of estrogen is even more pronounced among women with high baseline risk of heart disease.

Grodstein, F., & Stampfer, M. J. (1998). Estrogen for women at varying risk of coronary disease. Maturitas, 30(1), 19-26. doi:10.1016/S0378-5122(98)00055-3

Circulation (1999)

This study examined the effects of estrogen and progesterone on human foam cell formation, a key early event in arterial plaque buildup.

CONCLUSION: Physiological levels of estrogen and progesterone are associated with a reduction in human macrophage lipid loading in women, which is consistent with an atheroprotective effect.

McCrohon, J. A., Nakhla, S., Jessup, W., Stanley, K. K., & Celermajer, D. S. (1999). Estrogen and progesterone reduce lipid accumulation in human monocyte-derived macrophages. Circulation , 100(23), 2319-2325.

Annals of Internal Medicine (2000)

Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease.

Grodstein, F., Manson, J. E., Colditz, G. A., Willett, W. C., Speizer, F. E., & Stampfer, M. J. (2000). A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Annals of Internal Medicine, 133(12), 933-941.

(Note: This study also found that when they used synthetic, artificial progestins such as Provera (rather than natural, bio-identical progesterone) and combined it with estrogen pills (rather than creams which aren’t metabolized in the liver), it can increase the risk of stroke in certain patients. Artificial progestins should never be used; bio-identical progesterone is the appropriate choice for every patient. There are a number of variables that determine whether oral estrogen vs. estrogen cream is the right choice for a given patient. These nuances will be thoroughly discussed in person prior to initiating hormone replacement therapy.)

From the Women's Health Initiative:

Feb 2006: Findings on estrogen-only therapy from the Women’s Health Initiative trial were published:

Among women who started estrogen replacement therapy between ages 50 to 59, the risk of heart attack or coronary death was lower with estrogen use (Hazard Ratio= 0.63; 95% CI, 0.361.08, P>.05), and the risk of undergoing coronary artery bypass surgery or getting a stent was significantly lower with estrogen than with placebo (HR, 0.55; 95% CI, 0.35?0.86).

Hsia J, et al; Women’s Health Initiative Investigators. Conjugated equine estrogens and coronary heart disease: the Women’s Health Initiative. Arch Intern Med. 2006;166:357?365.

April 2007: A subanalysis was published that combined both arms of the Women’s Health Initiative. They again found that heart disease decreased with hormone replacement therapy: Estrogen users who were less than 10 years past menopause had a Hazard Ratio for Coronary Artery Disease of 0.76 (95% CI, 0.5?1.16).

June 2007: A separate subanalysis was published assessing estrogen use and coronary artery calcification in WHI participants who had undergone hysterectomy and who were 50 to 59 years old at baseline. Coronary artery calcium scores were more favorable among women receiving estrogen than among those receiving placebo (P=.02).

January 2008: The American Association of Clinical Endocrinologists released a statement on hormone replacement therapy, stating it may be beneficial for women in early menopause.

The re-evaluation of the Nurses’ Health Study found that women beginning hormone therapy near menopause had a significantly reduced risk of coronary heart disease (RR= 0.66 for estrogen alone; 0.72 when they added in synthetic progestin).

(Note: Many studies have shown that synthetic progestins negate the beneficial effects of estrogen on heart disease. This is why only natural bio-identical progesterone should be used: it maintains the beneficial effects of estrogen on heart disease, while also protecting against cancer of the breast, uterus and ovaries.)

A meta-analysis of 23 trials of hormone replacement therapy found that women who started taking estrogen either before age 60 or within 10 years of menopause had a significantly lower risk of Coronary Heart Disease (0.68), whereas if they waited until ten years post-menopause there was no benefit regarding CHD or Alzheimer’s (though there are still benefits regarding osteoporosis and skin elasticity).

In the Women’s Health Initiative they found similar results: the hazard ratio for CHD was 0.76 if they started hormones within ten years of menopause, but higher after age 60.