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June 26, 2019  
UTERINE NEWS: Feature Story

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  • uterus estrogen replacement

    Estrogen Replacement Lowers Fracture Risk but Increases Rates of Stroke


    May 05, 2004

    By Stephanie Riesenman for Uterus1

    The latest findings from the Women’s Health Initiative Trial show that estrogen replacement alone lowered the incidence of fractures and some cancers in postmenopausal women, however the incidence of stroke was higher with estrogen use.

    "At present, these data demonstrate no overall benefit of [estrogen therapy] for chronic disease prevention in post-menopausal women and thus argue against its use in this setting," wrote the doctors on the Women’s Health Initiative Steering Committee.

    Their findings were published in the April 14th issue of the Journal of the American Medical Association. In it they report on seven years of follow-up of nearly 11,000 women, aged 50 to 79 years, who were randomly selected to blindly take oral estrogen supplements, brand name Premerin, or a placebo.

    This study was one of two parallel trials on hormone replacement therapy (HRT) known as the Women’s Health Initiative. The other was the estrogen plus progestin versus placebo trial, which was halted prematurely in July of 2002 when doctors observed an increased risk of heart disease, stroke, blood clots, and breast cancer in the hormone therapy group.

    The estrogen-only trial was continued until February of this year because the health risks versus benefits had not been adequately determined in 2002. The researchers wanted to find out if hormone replacement would lower the risk of coronary heart disease in postmenopausal women without raising their risks of cancers or other major diseases.

    The researchers report that after nearly seven years on (HRT), estrogen alone does not appear to affect the risk of heart disease—including heart attack, silent heart attack, or death due to congestive heart failure. The difference was 49 deaths if taking estrogen versus 54 deaths with placebo per every 10,000 women. The slight benefit with estrogen therapy was observed early in the follow-up period, but diminished over time.

    Furthermore, the researchers found an increased risk of stroke for women in the estrogen group that was similar to the risks identified for women in the estrogen plus progestin trial. This incidence of stroke was increased by 39% in the estrogen group, which equates to an excess of 12 additional strokes per 10,000 women a year. The risk of stroke emerged early in the study and persisted throughout the seven years of follow-up.

    Unlike the first WHI study of combined hormone therapy that showed an increased risk of breast cancer with HRT use, women in the estrogen only group of the second trial had a 23% lower diagnoses rate of breast cancer. However, the data was not strong enough to make the conclusion that estrogen therapy reduces the risk of breast cancer, and therefore requires additional investigation.

    “The trend toward a reduction in breast cancer incidence was unanticipated and is opposite of that observed in the WHI estrogen plus progestin trial, which reported a 24% increased risk,” wrote the researchers.

    The researchers also found that fracture rates were lower in the estrogen group by 30% to 39%. Specifically, the incidence of hip fracture and spinal fractures went from 17 fractures per 10,000 patients down to 11 per 10,000 patients a year with estrogen replacement. Osteoporotic-related fractures decreased from 195 to 139 fractures per every 10,000 women a year.

    Among all the outcomes measured, the researchers reported that the effects of estrogen therapy were not affected by race/ethnicity or body mass. They also said that the results of this study apply only to estrogen administered orally, and they do not apply to other formulations of estrogen.

    In conclusion, the researchers write, "Based on these findings, women and their health care professionals now have useable risk estimates for the benefits and harms of [estrogen therapy] alone. Women considering taking [estrogen] should be counseled about an increase risk of stroke but can be assured about no excess risk of heart disease or breast cancer."

    They also recommend that women follow the Food and Drug Administration recommendations to use estrogen replacement at the smallest effective dose for the shortest possible time.

    Last updated: 05-May-04

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