OBJECTIVES. To evaluate the long-term population-level impact of E-HRT on cause-specific and all-cause mortality in postmenopausal women in the USA, using the results of the 2017 Women’s Health Initiative HRT Trial 2 update.1 Of particular interest was the significantly reduced Breast Cancer [BrCa] mortality rates [RR=0.55, 95% C.I.=0.33-0.92].1

METHODOLOGY. In the WHI HRT Trial 2, women were randomized to receive estrogen (E) or placebo (P).1 For our analyses, the Annualized mortality rates (AR) were extracted for women aged 50-59, 60-69, 70-79, for breast cancer, Alzheimer's dementia, and all-cause mortality. The Median follow-up was 18 years. The Annualized Mortality Rate Difference (ARD) between the two groups was calculated as a difference of the AR between the P vs. E (AR in P - [minus] AR in E), expressed per 100,000 person-years. Subsequently, the Number of Avoided Deaths per year (NAD/year) was calculated using the number of women in each age group from the 2010 US census data.

RESULTS. The annualized number of deaths avoided by the use of E-HRT in the US population was estimated as follows: BrCa, 9,292; Alzheimer’s dementia: 18,966; and all cause-mortality: 50,008 (Table).

CONCLUSIONS. These data show a major beneficial impact of E-HRT, with over 50,000 deaths/year prevented in the USA alone. While these gains, sustained throughout the follow-up, represent undoubtedly major multi-organ metabolic benefits of estrogen, the most striking and unexpected findings involve BrCa, with over 9,000 BrCa deaths potentially avoided each year, just in the USA alone.

RECOMMENDATION. Adoption and implementation of E-based HRT to the current HRT medical guidelines, to extend the health benefits to millions of women, and to prevent thousands of deaths each year in the USA alone.

REFERENCE.1.Manson JE et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials. J Am Med Assoc 2017; 318(10): 927-938.

AgesAge 50 – 59(N=21,506,008)Age 60 – 69(N=15,323,140)Age 70 – 79(N=9,169,601)ALL ages(N=45,998,749)
ARD / 100,000NAD / YearARD / 100,000NAD / YearARD / 100,000NAD / YearNAD / Year
Breast Cancer 20 4,301 23 3,524 16 1,467 9,292 
Alzheimer’s Dementia 40 6,129 140 12,837 18,966 
All-Cause Mortality 150 32,259 50 7,662 110 10,087 50,008 
AgesAge 50 – 59(N=21,506,008)Age 60 – 69(N=15,323,140)Age 70 – 79(N=9,169,601)ALL ages(N=45,998,749)
ARD / 100,000NAD / YearARD / 100,000NAD / YearARD / 100,000NAD / YearNAD / Year
Breast Cancer 20 4,301 23 3,524 16 1,467 9,292 
Alzheimer’s Dementia 40 6,129 140 12,837 18,966 
All-Cause Mortality 150 32,259 50 7,662 110 10,087 50,008 

Citation Format: Joseph Ragaz, Shayan Shakeraneh, Hong Qian, Hubert Wong, John J. Spinelli, Kenneth S. Wilson. Estrogen-based hormone replacement therapy [E-HRT] reduces all-cause, breast cancer, and Alzheimer's dementia mortality [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-05.