摘要：Objectives. We examined the effect of estrogen avoidance on mortality rates among hysterectomized women aged 50 to 59 years. Methods. We derived a formula to relate the excess mortality among hysterectomized women aged 50 to 59 years assigned to placebo in the Women’s Health Initiative randomized controlled trial to the entire population of comparable women in the United States, incorporating the decline in estrogen use observed between 2002 and 2011. Results. Over a 10-year span, starting in 2002, a minimum of 18 601 and as many as 91 610 postmenopausal women died prematurely because of the avoidance of estrogen therapy (ET). Conclusions. ET in younger postmenopausal women is associated with a decisive reduction in all-cause mortality, but estrogen use in this population is low and continuing to fall. Our data indicate an associated annual mortality toll in the thousands of women aged 50 to 59 years. Informed discussion between these women and their health care providers about the effects of ET is a matter of considerable urgency. In the 1990s, estrogen therapy (ET) became the standard of treatment of the almost 600 000 women a year in the United States undergoing hysterectomy. Clinical studies had indicated ET was effective for treatment of menopausal symptoms and appeared to be bone protective and cardioprotective. More than 90% of hysterectomized women in their 50s used ET, with a continuance rate averaging 4 to 5 years. 1–3 In July 2002, the Women’s Health Initiative (WHI) published the results of the Estrogen Plus Progestin Trial and announced that the study was being terminated ahead of schedule because of adverse effects in the women receiving hormones compared with those receiving placebo. 4 The media impact was immediate, widespread, and persistent. 5 The study’s treatment drug (Prempro) was often referred to as “HT” (hormone therapy) or “estrogen.” As a consequence, the findings were generalized to all varieties of hormone replacement, including estrogen alone, in women without a uterus although only women with a uterus were randomized in this study. Prescriptions for postmenopausal hormone replacement declined precipitously. Within 18 months, half of the women in the United States using systemic HT stopped treatment. 1–3 Included were almost 2 000 000 women who had no uterus who were using ET and not using the study drug. Subsequently, the findings of the WHI Estrogen-Alone Trial (WHI-ET) for women without a uterus were published for the intervention phase (2004) and the postintervention long-term follow-up phase (2011). 6,7 These findings showed mortality benefits for ET compared with placebo. Preliminary subgroup analysis of the intervention phase data (2004) indicated reduced total mortality in the women aged 50 to 59 years. However, it is only in the postintervention data (2011) that an absolute total mortality risk reduction of 13 per 10 000 women per year was reported for these women. The mortality decrease was almost entirely owing to a decrease in coronary heart disease (CHD) although reduced cancer mortality and other cause mortalities were also reported among the women who received ET. 7 Despite the positive findings for ET, prescriptions for all forms of systemic HT have continued to decline. 3,8–11 Currently, less than one third of hysterectomized women are using ET. 12 The decline in ET prescription and usage seems to reflect a generalized avoidance of any form s of HT not supported by the WHI data. This raises the possibility that there has been and continues to be a considerable resultant mortality toll. We therefore undertook an analysis, on the basis of published data, to determine the likely toll of excess, premature death among hysterectomized women aged 50 to 59 years in the United States following the WHI publication in 2002.
