Data from the Women's Health Initiative Memory Study (WHIMS) were published today in the Journal of the American Medical Association (JAMA). The WHIMS article reported that estrogen therapy does not decrease, but may increase, the risk of probable dementia in women age 65 and older using hormones compared to women taking placebo.
Physicians should consider these data as part of the individualized assessment of the appropriateness of postmenopausal hormone therapy. According to Wyeth Pharmaceuticals, a division of Wyeth, however, these data may not directly apply to newly menopausal women, a group not studied in WHIMS.
"Age is the predominant difference between the women who use hormone therapy in current clinical practice and the women evaluated in WHIMS," says Gary L. Stiles, M.D., executive vice president and chief medical officer, Wyeth Pharmaceuticals. "The women in the WHIMS trial were on average nearly 20 years older than the typical newly menopausal woman. In addition, it is well established that risk of dementia increases dramatically with age, with or without hormone use."
The majority of women in WHIMS had never previously taken postmenopausal hormone therapy. Previously published data from epidemiologic studies of dementia (among women largely using estrogen-alone therapy) have suggested that the initiation of hormone therapy at the onset of menopause may not have a detrimental effect. There are no prospective clinical studies that have evaluated this observation.
The WHIMS estrogen plus progestin data, originally published in May 2003, is already reflected in product labeling. Wyeth will work with the FDA to update the labeling for its postmenopausal hormone therapy products to include the latest data. The Company continues to recommend that hormone therapy be prescribed at the lowest effective dose for the shortest duration consistent with a woman's treatment goals and risks.
The WHIMS Data
WHIMS, a sub-study of the Women's Health Initiative (WHI) Study, evaluated approximately 28 percent of the women in WHI. Because the absolute risk of dementia is low in early menopause, but increases with age, WHIMS was designed to evaluate only the older women in the WHI Study. The original study design called for combining data from the WHI estrogen-alone and estrogen plus progestin groups to achieve adequate statistical power for the planned WHIMS analyses.
When the estrogen-alone and estrogen plus progestin data were combined, the authors reported a statistically significant increase in the risk of probable dementia (RR 1.76, CI 1.19 - 2.6, P = 0.005). These data translate to 18 additional cases of probable dementia per 10,000 women per year. The WHIMS estrogen-alone data showed a trend toward an increase in probable dementia; however, it did not reach statistical significance (RR 1.49, CI 0.83 - 2.66, P = 0.18).
In a separate report also published in this week's issue of JAMA, the WHIMS investigators report the effects of estrogen-alone and estrogen plus progestin on specific tests of cognitive function. The authors report that hormone therapy did not improve global cognitive function in a population of women age 65 and older, and may adversely affect it in some women.
WHIMS evaluated the 0.625 mg strength of PREMARIN® (conjugated estrogens tablets, USP) and the 0.625 mg/2.5 mg strength of PREMPROTM (conjugated estrogens/medroxyprogesterone acetate tablets). Today, a number of lower doses of PREMARIN and PREMPRO are widely available and commonly prescribed.
Wyeth is providing an online resource - www.estrogeninfo.com - where clinicians and women can get more information about the WHIMS announcement from a variety of authoritative sources.
Appropriate Use of Hormone Therapy
The absolute risk of dementia is low in early menopause. In current clinical practice, estrogen alone is prescribed primarily for women who have undergone surgical menopause (average age 42), and estrogen plus progestin is prescribed primarily for women who have entered natural menopause (average age 51).
Most women who initiate hormone therapy do so for the relief of menopausal symptoms. The Women's Health Initiative (WHI), including the WHIMS sub-study, did not evaluate the use of hormone therapy for menopausal symptom relief or its other indicated uses.
Hormone therapy remains a valuable treatment for symptomatic postmenopausal women and is the only therapy indicated for the relief of menopausal symptoms, including hot flashes, night sweats, and vaginal atrophy, and the prevention of postmenopausal osteoporosis. It has never been indicated, and should not be used, for the prevention or treatment of dementia or mild cognitive impairment.
Wyeth continues to support the appropriate use of postmenopausal hormone therapy for its labeled indications. Hormone therapy should be prescribed at the lowest effective dose and for the shortest duration necessary for a woman to achieve her treatment goals, with consideration given to her individual risk profile.