In addition to my usual Friday website article, I felt it was necessary to address the recent JAMA article on estrogen-only therapy (in women who have had a hysterectomy.) The women were followed and results have just been published years after the Women’s Health Initiative (WHI) was stopped. The American Menopause Society (NAMS) said it best and hence I am simply forwarding the message that appeared on their website in response to this article. Once more, their conclusions reinforce the fact that estrogen (without a progestin) did not increase, but actually decreased breast cancer, in follow-up of over 10 years. Premarin (CEE) therapy was found to be beneficial vis a vis heart disease, colorectal cancer and overall, all-cause mortality for women under the age of 70 but appeared to lose its benefits and indeed worsen mortality rates after the age of 70. So here is the data and the NAMS conclusion:
Brief summary of the article: The final results of the Women’s Health Initiative Estrogen-Alone Trial, reflecting a median of 6 years of treatment and an average of 10.7 years of follow-up, are published in this article. The long-term follow-up and post-stopping findings for this trial have not been previously reported. The authors examined health outcomes in 10,739 women with prior hysterectomy, comparing those randomized to receive CEE treatment versus placebo. The median duration of adherence (taking >80% of study pills) to CEE was 3.5 years.
The main outcomes were CHD and invasive breast cancer. In addition, a global index of risks and benefits included CHD, stroke, pulmonary embolism, breast cancer, colorectal cancer, hip fracture, and death.
Results: For the overall study population, there was a significantly reduced risk of invasive breast cancer among women randomized to CEE versus placebo over the 10.7 years of follow-up (23% reduction; HR 0.77; 95% CI, 0.62-0.95). Risk reductions were similar in the treatment and post-stopping periods. In the overall study population, there was no significant effect of CEE on CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. However, younger women (ages 50-59 at enrollment) tended to have much more favorable outcomes on CEE than the older women for CHD, heart attack, colorectal cancer, all-cause mortality, and the global index. For heart disease endpoints, risks were 40% to 50% lower with CEE than placebo in women ages 50 to 59 but were higher with CEE than placebo in women ages 70 to 79. For example, for every 10,000 women per year taking CEE, there were 12 fewer heart attacks, 13 fewer deaths, and 18 fewer adverse events for women ages 50 to 59. In contrast, for every 10,000 women per year ages 70 to 79, there were 16 extra heart attacks, 19 extra deaths, and 48 extra adverse events for women taking CEE (P values for interaction by age were statistically significant).
Conclusions: In this randomized trial, conjugated equine estrogens (CEE) use was associated with a decreased risk of invasive breast cancer and much more favorable results for coronary heart disease (CHD), all-cause mortality, and several other outcomes in younger than in older women. Overall, the observed pattern provides more support for the “timing hypothesis.” The findings highlight the differences between estrogen alone and estrogen plus progestin in terms of breast cancer risk and other chronic disease outcomes, as well as important differences by age group. Whether the reduction in breast cancer risk with CEE alone will apply to all women at menopause and to estradiol or other formulations of estrogen, and whether it will persist with longer-term estrogen use, remains unknown.