Heart disease is the Number One cause of death for women in this country, and now worldwide. The risk of heart disease—coronary artery disease—increases in post-menopausal women, whether their menopause is natural, surgical, or premature. For years, we believed that estrogen was protective with respect to the heart, and we routinely prescribed hormone replacement therapy (HRT) to reduce or negate this increased risk. In women with intact uteruses, progestin is given with estrogen to protect the uterus from growing too thick (uterine hyperplasisa). Therefore, the use of estrogen alone is restricted to women who have had a hysterectomy. Nationwide, approximately, one-third of women in their 50s have had a hysterectomy.
Initially, observational studies showed that women who took HRT improved their cholesterol levels and decreased their risk of heart disease. But women who took HRT also tended to be of a higher socio-economic class, visited their doctors more regularly, and generally had healthier lifestyles, which could also account for their decreased risk. The first randomized clinical trial of combined HRT, the Heart and Estrogen/Progestin Replacement Study (or “HERS” trial), reported results in 1998. It studied 2,763 post-menopausal women, average age 67, with known coronary heart disease. It found that starting women on HRT increased their risk of heart events (including heart attacks) in the first year compared with women on placebos, but by the fourth and fifth years, women taking the hormones had fewer heart events. The risk for recurrent major heart events was increased among short-term users with previous coronary disease, but then decreased with longer-term use. Women taking HRT also experienced more blood clots and gall bladder disease.
Then, the Women’s Health Initiative (WHI) came along—the largest women’s health study in U.S. history, which began in 1991 (with follow up through 2010). It looked at 161,808 generally healthy post-menopausal women aged 50-70.
The hormone replacement part of the trial focused on whether oral estrogen, alone or in combination with progestin, was beneficial in preventing heart disease. 16,000 women with intact uteruses were randomized to receive estrogen plus progestin or a placebo. In July 2002, after an average of 5.2 years’ follow-up, the trial was stopped early because the overall risk exceeded the benefit. The women taking combination HRT had more heart attacks, strokes, blood clots, and invasive breast cancers than women taking placebo. (The HRT group also had less hip fractures and colon cancer).
In the other arm of this study, 10,000 women without uteruses were randomized to either estrogen alone or a placebo. This trial was stopped after 7 years because of an increased risk of stroke in women receiving estrogen.
Once these results were reported, there was a general consensus that HRT should no longer be prescribed to reduce a women’s risk of heart disease—and in fact, it might increase it. It is important to note that the WHI study used conjugated equine estrogen, which is derived from the urine of pregnant mares (and marketed by Wyeth Pharmaceuticals under the name “Premarin” ). Preferred preparations today use estradiol, which is chemically more similar to a women’s natural estrogen. Some believe that this maybe healthier for women, but no large-scale study has been (or is likely to be) done to support this.
Finally, just last week, the Journal of the American Medical Association reported a follow-up of the Women’s Health Initiative. In the group taking estrogen alone—the women without uteruses—participants who began using estrogen in their 50s had fewer heart attacks, strokes, and blood clots compared with the placebo group. But for women who began using estrogens in their 70s, the heart attack risk was increased.
Additionally, women who took estrogen alone had a 23% lower risk of breast cancer compared with women taking a placebo. It is important to remember, however, that the WHI data has consistently shown that taking the combination of estrogen and progestin raises the risk of breast cancer.
So there you have it—the historical lowdown. Hormone replacement therapy is still prescribed by practitioners, myself included, to treat peri-menopausal symptoms. We do attempt to use the lowest doses for the shortest duration to achieve the desired results for our patients. In these patients, we of course judiciously screen for breast cancer and aggressively attempt to practice coronary heart risk reduction.
The bottom line for you? These new findings may allow women who are taking estrogen alone to feel a little better about their choice. They do not, however, support taking estrogen to prevent breast cancer or heart disease.
Peri-menopausal symptoms can be debilitating. The choice of whether or not to use hormone replacement therapy should be one that you make after careful consideration of your age and your risk factors in consultation with your gynecologist and internist.