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Hormone therapy: For the right patients, benefits outweigh risks

December 2003 · Vol. 15, No. 12

A young internist, describing a difficult situation, told me that her 52-year-old patient was distressed by severe vasomotor symptoms and sleep disturbances that were compromising the woman’s daytime effectiveness. The patient’s last menstrual period had occurred about 6 months before, and she had experienced no vaginal bleeding since that time. Except for the troubling vasomotor symptoms, the patient was healthy.

The internist said she would not be prescribing estrogen because the Women’s Health Initiative (WHI) had clearly and definitively determined that the risks exceeded the benefits. I was shocked by the strength of her conviction, but tried to conceal my surprise and concern. Instead, I encouraged her to talk in more depth about the patient’s situation. We reviewed her medical history, current medications, physical examination, and laboratory findings, and concluded that the patient was healthy except for her symptoms.

I explained that, given the vasomotor symptoms, low baseline risk for heart disease and breast cancer, and the effectiveness of estrogen treatment for menopausal symptoms, the patient was an excellent candidate for hormone therapy. The internist seemed surprised, and we arranged a time to talk at greater length about the WHI.

WHI’s fundamental findings

The WHI, a large randomized trial of hormone therapy, reported that, when compared with placebo, one form of estrogen plus progestin therapy (conjugated equine estrogen 0.625 mg daily plus medroxyprogesterone acetate 2.5 mg daily) was associated with 7 additional coronary heart events, 8 invasive breast cancers, 8 strokes, and 8 pulmonary emboli per 10,000 woman-years of treatment.

As for its benefits, hormone replacement therapy was associated with 6 fewer cases of colon cancer and 5 fewer hip fractures. Since the WHI was a prevention trial, very few women entered into the study had an indication for hormone therapy, such as vasomotor symptoms, and most had experienced the transition to menopause a decade before entering the study.

For moderate to severe symptoms, the benefits are clear

Most experts continue to believe that hormone therapy is indicated for treatment of moderate to severe vasomotor symptoms that impair a perimenopausal or menopausal woman’s quality of life. The benefits of hormone treatment in these women have been demonstrated in many randomized studies. In almost all trials that examined quality of life as an endpoint, treatment of moderate to severe vasomotor symptoms with estrogen or estrogen-progestin was associated with an improvement in the quality of life.1 WHI data support this treatment paradigm.

In women at low risk for heart disease and breast cancer, hormone therapy is associated with a minimal increase in the absolute risk for these 2 diseases. In a subanalysis of the WHI, women who were more than 20 years past onset of menopause were at the greatest risk of a heart attack after starting hormone therapy. In contrast, women less than 10 years past the onset of menopause appeared to have no markedly increased absolute risk of heart attack after hormone therapy was initiated.

This is logical, since women within 10 years of menopause are young and therefore have a low baseline risk for heart attack, while women 20 or more years beyond menopause face an increased risk because of their age alone.2

HT is the best available treatment for ‘young’ women

For the healthy “young” woman—ie, recently perimenopausal or menopausal—with significant vasomotor symptoms, the benefits of hormone therapy are likely to outweigh the risks. With up to 3 to 4 years of use, the increase in breast cancer risk should be minimal.

The bottom line is that estrogen and estrogen-progestin–containing products are the best pharmacologic treatments available for moderate to severe vasomotor symptoms and sleep disturbances associated with hypoestrogenism.

As noted by the US Food and Drug Administration, these agents should be used at the lowest effective dose and for the shortest duration for the individual woman to reach her treatment goal.

Case outcome

After our discussion, the internist agreed to counsel her patient differently, given the woman’s age and low baseline risk of heart disease and breast cancer.

After a conversation about the benefits and risks of hormone replacement therapy, the patient did start taking an estrogen-progestin formulation, and experienced a marked reduction in her vasomotor symptoms and sleep disturbances.

Women menopausal for less than 10 years appeared to have no markedly increased absolute risk of heart attack.


1. Derman RJ, Dawood MY, Stone S. Quality of life during sequential hormone replacement therapy: a placebo-controlled study. Int J Fertil Menopausal Stud. 1995;40:73-78.

2. Manson JE, Hsia J, Johnson KC, et al. Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523-534.

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