HRT,HEART,MORTALITY
“The Window“
The Beneficial Effect of Hormone Therapy on Mortality and Coronary Heart Disease in Younger versus Older Postmenopausal Women
Posted 02/29/2008
Howard N. Hodis, MD; Wendy J. Mack, PhD
Author Information
Introduction
Although the public portrayal of systemic hormone therapy (HT; encompassing both estrogen-alone therapy [ET] and estrogen-progestogen therapy [EPT]) as a preventive therapy is negative, the actual data paint an opposite picture when viewed for the appropriate subgroup of women. The totality of data indicate that the window of opportunity for reducing total mortality and coronary heart disease (CHD) with HT is initiation within 6 years of menopause and/or before age 60 and continued for 5 years or more. Randomized controlled trials (RCTs) have shown that the risks of HT are rare (<1/1,000), especially in younger postmenopausal women, and comparable to other primary prevention therapies. The data supporting HT as a primary prevention therapy for CHD that additionally reduces total mortality when initiated in young postmenopausal women in close proximity to menopause will be summarized.
Overview
Contrary to the many consistent observational and case-control studies that support the reduction of CHD with HT, RCTs have shown no apparent benefit.[1] However, it is now understood that the characteristics of women who participated in these observational studies differed markedly from those of women enrolled in RCTs ( Table 1 ). Data indicate that the discordance in findings between observational studies and RCTs is likely related to age and timing of initiation of HT relative to the onset of menopause.[1]
The majority of women who participated in observational studies were younger than age 55 and within 2 years after menopause when HT was initiated. Conversely, women enrolled in RCTs were, on average, aged 63 to 67 years and more than 10 years postmenopause. When data from RCTs were analyzed across the entire age range of the participants, the effects of HT on CHD were null. However, when analyzed by age and time since menopause, RCTs are in agreement with observational studies indicating that HT reduced both total mortality and CHD when initiated in younger postmenopausal women in close proximity to menopause.
In contrast, RCTs indicate that when initiated in older postmenopausal women distant from menopause, HT has a null effect on total mortality and potentially an adverse effect on CHD. The distinct difference in outcomes between these two subgroups of women accounts for the apparent discordance between observational studies and RCTs, a conclusion also reported from the Women’s Health Initiative (WHI) ( Table 2 ).[2]