Rise in mortality risk seen in hysterectomized women not using estrogen therapy

A severe decline in the use of estrogen therapy (ET) due to misunderstanding the findings of the Women’s Health Initiative (WHI) Estrogen Plus Progestin Trial has particularly affected hysterectomized women in their 50s, leading to excess mortality, according to a study published online in the American Journal of Public Health.

Philip M. Sarrel, MD, emeritus professor of obstetrics and gynecology and psychiatry, Yale University School of Medicine, David Katz, MD, the Yale-Griffin Research Center, and colleagues extrapolated the mortality data reported in the 2011 WHI trial regarding women after hysterectomy and applied it to the general population of such women in the United States.

The researchers used census data for the numbers of women in different age groups; hospital procedure code data for the rate of hysterectomy; and published reports doctor/patient practices and pharmacy records to establish the reduction in use of hormone replacement since the WHI data were published in 2002.

“In essence, we simply asked and answered this question: ‘What would it mean if the survival advantage seen with estrogen in the WHI extended to the whole population of similar women in the United States?’ That, of course, is just what clinical trial data are supposed to be for: to help us know how best to treat patients like those in the trial,” said Dr. Sarrel.

Application of the WHI findings that mortality was increased in placebo-treated versus estrogen-only treated hysterectomized women aged 50 to 59 years enabled a calculation of excess mortality for women fitting this profile between 2002 and 2011, according to Dr. Sarrel.

There are 22 million 50 to 59 year olds among whom 8 million have had a hysterectomy in the United States today. Not using estrogen translates to an excess of mortality of 13 per 10,000 per year among hysterectomized women, according to the WHI report, according to Dr. Sarrel.

“Women with menopause symptoms have greater economic costs with millions more visits for outpatient care and time lost from work compared to asymptomatic women,” he said.

The best point estimates show it is most likely between 40,292 and 48,835 excess deaths due to avoiding ET during these years. There may have been as few as 18,601 and as many as 91,610 deaths, according to Dr Sarrel.

The study was prompted by the publication in JAMA in April 2011 of long-term follow-up data for estrogen-only versus placebo-treated women in the WHI. This paper identified a subgroup of women (hysterectomized, aged 50 to 59 years) who had a decrease in breast cancer, a decrease in myocardial infarction, and a decrease in mortality (13/10,000/yr) if they received ET.

“Evidence-based medical practice originates with such findings from randomized clinical trials by extrapolating the findings to the whole population,” Dr. Sarrel said.