Does Hormone Replacement Therapy (HRT) Prevent Heart Disease in Women?
By Doug Bremner

It was long felt that estrogen and progesterone (which decline after menopause) had a protective effect against heart disease. This assumption was never tested in properly controlled trials, until tens of thousands of women were unnecessarily exposed to hormone replacement therapy (HRT) for the prevention of heart disease. There was supposedly the added benefit that HRT would make you look better and improve your sex life.

The original evidence that HRT prevented heart attacks was based on what are called observational studies. Women who chose to take HRT were compared to those who didn't, and were found to have fewer heart attacks. It turned out that women who took HRT also were more concerned about their health. They did other things, like exercise and diet that were beneficial for heart attack. The HRT didn't do anything. However ten years went by with major marketing to women and billions of dollars in sales. The pharmaceutical companies had hit on the mother load of all markets. Not just patients with a disease, but all women over age 50.

The observational study design, however, is inherently flawed for the study of medications. It is easy to have some systematic factor creep in that will skew the results. The only way to answer a question like does HRT prevent heart attacks, is to do a controlled study where women get either HRT or a sugar pill, they don't get to choose which one, and they (and their doctors) don't know what they are on. At the end of five years, you compare outcomes (i.e. heart attacks) between the two groups. It took so long to do such studies because it was argued that it would be unethical to give a sugar pill to women when HRT had such obvious benefits.

In the more recent controlled trials not only did HRT (estrogen and progesterone) not prevent heart attacks, it actually increased them. There was a statistically significant 24% increase in risk of heart attack or cardiac death with equine estrogen and medroxy-progesterone (Prempro) in the Women's Health Initiative (WHI) study (Manson et al 2003) while another study, the Heart and Estrogen/Progesterone Replacement (HERS) study found no protective effect in women with a history of heart disease (Grady et al 2002; Hulley et al 1998) HRT also increased the risk of breast cancer by 24% (Chlebowski et al 2003) stroke by 41%, and doubled the risk of pulmonary embolus (blood clot in the lung) (WGWHII 2002). For every one hundred women treated with HRT in WHI, one woman developed a serious adverse event directly related to the HRT. In the HERS study, there was a 10% increase in mortality with HRT, related in part to a doubling of the risk of potentially lethal blood clots (Hulley et al 2002; Hulley et al 1998). Another study showed that HRT accelerated the progression of thickening of the coronary arteries, and doubled the risk of dying of heart disease (Waters et al 2002). Based on these findings, there is no role for HRT in heart disease prevention.

Chlebowski RT, Hendrix SL, Langer RD, et al (2003): Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women's Health Initiative Randomized Trial. Journal of the American Medical Association 289:3243-3253.

Grady D, Herrington DM, Bittner V, et al (2002): Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progesterone Replacement Study Follow-up (HERS II). Journal of the American Medical Association 288:49-57.

Hulley S, Furberg C, Barrett-Connor E, et al (2002): Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progesterone Replacement Study Follow-up (HERS II). Journal of the American Medical Association 288:58-66.

Hulley S, Grady D, Bush T, et al (1998): Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Journal of the American Medical Association 280:605-613.

Manson JE, Hsiao J, Johnson KC, et al (2003): Estrogen plus progestin and the risk of coronary heart disease. New England Journal of Medicine 349:523-534.

Waters DD, Alderman EL, Hsia J, et al (2002): Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: A randomized controlled trial. Journal of the American Medical Association 288:2432-2440.

WGWHII (2002): Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative Randomized Controlled Trial. Journal of the American Medical Association 288:321-333.

Learn more about alternatives to medications and hidden risks of prescription medications in 'Before You Take That Pill: Why the Drug Industry May be Bad for Your Health: Risks and Side Effects You Won't Find on the Label of Commonly Prescribed Drugs, Vitamins and Supplements,' by researcher and physician J. Douglas Bremner, MD.