Estrogen-only arm of WHI stopped because of increased stroke rate

[Guest guest]

Rheumawire

Mar 3, 2004

Estrogen-only arm of WHI stopped because of increased stroke rate

Bethesda, MD - The estrogen-alone arm of the Women's Health Initiative

(WHI) has been stopped after almost seven years of follow-up because of

an increased risk of stroke in the treatment group.

However, unlike combined hormone treatment with estrogen and progestin,

estrogen alone did not appear to affect (either increase or decrease)

heart disease or increase the risk of breast cancer. Like the combined

therapy, it showed a reduction in the risk of hip fracture.

The increased risk of stroke in the estrogen-alone study is similar to

that found in the estrogen-plus-progestin arm of the WHI trial, which

was stopped in 2002 and showed that women on hormone therapy had eight

more strokes per year for every 10 000 women than those taking the

placebo. The National Institutes of Health, which sponsored the study,

says that an increased risk of stroke is not acceptable in healthy women

in a research study. This is especially true if estrogen alone does not

affect heart disease, as appears to be the case in the estrogen-only

study.

The NIH also notes the results of the estrogen-only study would not

likely change if the trial continued to its planned completion in 2005.

Furthermore, it says that enough data have been obtained to assess the

overall risks and benefits of the use of estrogen in this trial, and

full results will be reported in the next two months.

A separate report will contain information on probable dementia and/or

mild cognitive impairment in the women age 65 and older who participated

in the estrogen-alone WHI-Memory Study (WHIMS), an ancillary study of

the WHI hormone trials. Preliminary data suggest that for the WHIMS

participants who were on estrogen alone, compared with the women who

were taking placebo, there was a trend toward increased risk of probable

dementia and/or mild cognitive impairment. An increased risk of dementia

was also seen in the estrogen-plus-progestin arm of the studythis was

reported last year.

Dr Herrington (Wake Forest University, Winston-Salem, NC), who has

been involved in other HRT trials in heart disease, commented to

rheumawire that these results did not change things substantially for

women with respect to HRT and heart disease. " The risk of stroke is

small in absolute terms, but it still needs to be recognized. These

results may suggest that it is the progestin that causes most of the

harm in HRT, but we need to see the data before drawing any firm

conclusions. I suspect that this will be the subject of a great deal of

debate, " he added.

The estrogen-alone study involved 11 000 healthy postmenopausal women

aged 50 to 79 years who had had a hysterectomy. They were randomized to

conjugated equine estrogen (Premarin®, Wyeth-Ayerst) 0.625 mg/day or

placebo. The NIH decision to stop the estrogen-alone trial was made on

February 2, 2004.

The estrogen-plus-progestin trial was stopped after 5.6 years of

follow-up because of an increased risk of breast cancer in the treatment

group and because the risk of breast cancer, coronary heart disease,

stroke, and thrombosis outweighed the benefits on hip fracture and

colorectal cancer.

The NIH advises women to continue to follow the FDA guidance regarding

hormone therapy for the treatment of menopausal symptoms. For the

prevention of osteoporosis, it says that hormones should be considered

only for women at significant risk who cannot take nonestrogen

medications. The FDA recommends that estrogens and progestins should be

used at the lowest doses for the shortest duration needed to achieve

treatment goals.

Amazingly, Wyeth shares rose slightly on the latest results from the WHI

study. The company issued a press release saying the findings were " good

news for many women who have had a hysterectomy and their physicians who

want to prescribe estrogen to relieve moderate to severe menopausal

symptoms. " It added: " WHI provides valuable information for women who

are at the point where they must consider estrogen for prevention of

osteoporosis. "

The WHI involves more than 161 000 women who are either participating in

a set of clinical trials to test preventive measures for heart disease,

fractures, and breast and colorectal cancer or in a large observational

study. In addition to the trials of estrogen alone and estrogen plus

progestin, other WHI trials are studying a low-fat eating pattern and

calcium/vitamin D supplements. These trials are continuing.

Sue

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org