July 2009

Current Trends in Hormone Therapy

This is the first of a three-part series on Current Trends in Hormone Therapy. Over the next several weeks, you can look forward to receiving information that builds upon this topic.

Part 1: Estrogen Therapy: Changes in Use
In 1995, approximately 38% of postmenopausal women in the United States were taking hormone therapy. At that time, several observational studies had suggested that hormone therapy offered women some protection against coronary heart disease and osteoporosis. A decision analysis published in 1997 concluded that the benefits of hormone therapy outweighed its risks for nearly all women. More recently, the results from 2 large randomized clinical trials, the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), have demonstrated that the risks associated with hormone therapy outweigh the benefits for women taking continuous estrogen and progestin regimens. The results of these trials prompted the U.S. Food and Drug Administration to require new warning labels for all estrogen products. In addition, the U.S. Preventive Services Task Force revised its assessment of hormone therapy to recommend against the routine use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women.

Before the publication of HERS, the use of hormone therapy was increasing at a rate of approximately 1% per quarter. Following the publication of HERS, there was a decrease in use of about 1% per quarter. In contrast, the publication of the WHI was associated with a decline in use of 18% per quarter. Substantial declines in hormone therapy use were seen for most subgroups of women, including women with a previous hysterectomy, women older than 65 years of age, and women from several racial or ethnic groups.

WHI and Updates
The WHI studies were conducted on women aged 50 years or older without menopausal symptoms, most of whom were 10 years or more beyond menopause. In brief, the estrogen-alone study found that compared with placebo, oral estrogen was associated with no difference in risk for heart attack, increased risk of stroke, increased risk of blood clots, an uncertain effect on breast cancer, no differ ence in risk for colorectal cancer and reduced risk of fracture.2,3 In a substudy of women aged ≥65 years, oral estrogen was also associated with no protection against mild cognitive impairment, and an increased risk of dementia.

The estrogen-progestin study found that hormone therapy was associated with increased risks of heart attack, stroke, blood clots, and breast cancer, reduced risk of colorectal cancer, fewer fractures, and, in a substudy in women aged ≥65 years, no protection against mild cognitive impairment and an increased risk of dementia.2-4 Updates to the WHI have tended to confirm the notion that the main study findings cannot always be generalized to the entire population of postmenopausal women. Some analyses have shown possible heart benefits in women aged 50 to 59 or in those starting hormone therapy 5 In the estrogen-alone study, coronary artery calcium (CAC) scores, which are predictive of coronary events, were lower with estrogen treatment versus placebo in women aged 50 to 59 years.6 A combined analysis of the two WHI studies has shown that:

Risk of heart attack may not be increased in women starting hormone therapy <10 years after menopause, but there is increasing risk in those 10 or more years beyond menopause5
Risk of stroke is increased regardless of when therapy is started or number of years from menopause

Risk of death from any cause appeared to be reduced in women who started therapy at age 50 to 59 years. However, this new, combined analysis from the WHI hormone trials does not change the current recommendation that hormone therapy should not be used for prevention of heart attacks. If hormones do not increase risk of heart attack at younger ages–and even if they reduce risk in these age groups–there is no certainty that any benefit will persist with long-term use into older ages