Until about 10 years ago, menopausal women were routinely advised to take hormone replacement therapy (HRT), including estrogen, to prevent heart disease, strengthen bones and improve mental and emotional health.

Then women began avoiding HRT when an important study announced in 2002 that it increased the risk for heart disease, stroke, pulmonary embolism and breast cancer.

Latest development: A new analysis of data from the same study indicates that for the estimated one-third of women over age 50 who have had a hysterectomy, using estrogen alone actually reduces breast cancer risk, while among the younger study participants, risk for heart disease was reduced. The new findings were reported in The Journal of the American Medical Association (see also page 35).

John E. Morley, MD, a leading gerontologist who also specializes in the study of hormones, answers questions concerning the latest findings…

  • Why has hormone replacement therapy for menopausal women become so controversial? A decade ago, more than one-third of postmenopausal American women were taking estrogen, alone or with other hormones, to help fight hot flashes, vaginal dryness and other menopausal symptoms.

HRT was assumed to be both effective and safe-but this assumption had never been tested in a large-scale clinical trial.

In 1991, the National Institutes of Health launched the Women's Health Initiative study to investigate the long-term health effects of HRT. The study, which included more than 160,000 women, was stopped early when investigators concluded that study participants on HRT with estrogen and the hormone progestin had a higher risk for stroke, breast cancer and other health problems than participants taking placebos.

Reports of the study had an immediate effect—the number of prescriptions for HRT decreased by 50% almost overnight. Today, millions of menopausal women refuse any form of HRT, even though this decision greatly increases their risk of getting osteoporosis.

  • Based on the original findings, aren't women correct in refusing HRT? In the original study, for every 100,000 women treated with estrogen and progestin, we would expect to see about seven additional cases of heart disease and about eight additional cases of cancer. It's a concern, but the risk for a particular woman is, on average, small.

Remember, these complications occurred only in women taking the two hormones.

  • Why is the new analysis important? The conclusions are different from the earlier ones, but only because the analysis looked at a different group of women-those who had previously had a hysterectomy (which surgically induces menopause with removal of the uterus) and were taking only estrogen (or a placebo), rather than the estrogen-progestin combination.

The results were striking. Women taking estrogen alone had a 23% lower risk of developing breast cancer than those in the placebo group. We don't know why estrogen was protective in this group.

No one is recommending that women take estrogen solely for breast cancer prevention However, this finding should be reassuring to the women who have had hysterectomies and are using estrogen therapy for relief from hot flashes or other menopausal symptoms.

  • Why were postmenopausal women historically instructed to take progestin if it's dangerous? Supplemental estrogen increases the risk for endometrial cancer. The addition of progestin mitigates that risk. It's not a perfect solution because progestin/estrogen has been linked to a slight increase in breast cancer. In the past, many doctors routinely prescribed the two hormones together. This was not the right approach for all women.

A woman who has had a hysterectomy obviously can't get endometrial cancer because she doesn't have a uterus. In these women, as the new analysis has shown, taking estrogen without progestin actually reduces breast cancer risk.

Important: Some types of breast cancer proliferate in the presence of estrogen. Women who have had estrogen-dependent cancers, or have a high risk of getting them due to such factors as obesity, also need to be cautious about estrogen-only therapy.

Women who still have their uteruses and are suffering from severe menopausal discomfort will be advised to continue using the combination treatment at the lowest possible dose and for the shortest period of time-say, for three to five years.

  • Does estrogen help or hurt the heart? While the original study found an increase in heart problems in women using a combination of estrogen and progestin, the new analysis found that the increase applied to only the older women who had had hysterectomies and took estrogen alone.

The researchers estimate that for every 10,000 women age 70 or older who are taking estrogen, there would be 16 additional heart attacks. It's possible that women in this age group already have advanced atherosclerosis.

Estrogen causes the coronary arteries to relax excessively. With existing atherosclerosis, this could dislodge unstable plaques (deposits) in the arteries and trigger a heart attack.

For younger women (generally age 59 or younger), the situation was the opposite. The analysis found that participants who had undergone a hysterectomy and started taking estrogen in their 50s had nearly 50% fewer heart attacks compared with those taking placebos.

My advice: It's clear from this study that older women who have had a hysterectomy probably should not start taking estrogen-the risks are likely to outweigh the benefits. Younger women without uteruses, on the other hand, can clearly benefit.

  • How young should a woman be to consider HRT? A woman without a uterus who is age 59 or younger and is experiencing moderate-to-severe menopausal symptoms or has a high risk of developing osteoporosis-due, for example, to low body weight-could benefit from estrogen.

We advise women who do use HRT to not exceed 10 years of use. The risks rise with longer use, with the highest risk for those who take it for 15 years or longer.

  • Are bioidentical forms of estrogen safer than prescription versions? This topic is controversial. One criticism of the Women's Health Initiative study is that the participants were given prescription Prempro or Premarin, conjugated estrogens made from mare's urine. However, study skeptics argue that estradiol, a so-called bioidentical hormone that's touted as being more similar to the estrogen produced by a woman's ovaries, is a safer choice.

Bioidentical forms of estrogen are typically synthesized from soy or yams, foods that contain estrogen-like compounds. Despite the fact that many women use bioidentical hormones, there's no clear evidence, in my opinion, that they're safer or more effective than traditional hormone therapy. Estrogen (traditional or bioidentical) in nonpill forms, such as creams or patches, may have fewer side effects because they are metabolized differently than the oral form. Ask your doctor for advice.

Women in my practice who have added soy and yams to their diets weren't able to get enough of the hormonelike substances from these foods to significantly improve menopausal symptoms.

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