The Estrogen Window - What Is It, and Why Should You Care?
If you’ve ever looked into hormone replacement therapy, you may have come across something called “the critical window hypothesis”, or “the opportunity window for estrogen”. The Estrogen Window, as we like to call it, is the time period during which studies show it is optimal to start menopausal hormone replacement therapy (HRT). Evidence supports that women who start estrogen within 10 years of menopause or before age 60 receive the most benefit - preservation of bone strength and elasticity, a lower risk of memory loss due to Alzheimer’s disease, and a lower rate of heart disease. Not only do women who choose to take HRT get the quality of life benefits of estrogen, the largest study ever done, the Women’s Health Initiative, showed a trend that subjects actually lived longer, too.
Why the window?
- When estrogen goes away, the receptors in the blood vessels start to decline.
- When estrogen goes away, the responsiveness of blood vessels starts to decline.
- When estrogen goes away, cholesterol and calcium plaques start being deposited in the lining of the arteries.
- Estrogen decreases deposition of calcium and cholesterol plaques in arteries.
- Blood vessels respond better to estrogen within the first 5 years after menopause - meaning they respond to estrogen’s message to dilate (open) more effectively within those first 5 years.
- After menopause, the number of estrogen receptors in women declines unless they take estrogen.
- Estrogen reduces plaque in the heart (coronary arteries) more effectively the sooner it is initiated after menopause in animal studies.
- Estrogen improves cardiovascular function and blood supply to organs by dilating blood vessels, increasing nitric oxide levels, lowering cytokines, and lowering inflammatory markers.
We knew the above basic benefits of estrogen, but researchers devised a study to test the hypothesis that the timing of initiation of estrogen replacement is important. This well-respected study published in the New England Journal of Medicine in 2016 called the ELITE trial showed that oral estrogen (estradiol) given within 6 years of menopause slowed the progression of plaque build up (cholesterol blockages which can cause heart attacks). 1 The ELITE trial supports the timing hypothesis in that it showed that oral estrogen did not provide the same benefit when started more than 10 years past menopause. 1 This proved that the timing of initiation of hormone therapy matters.
Another study showed that blood vessels respond best to estrogen within the first 5 years after menopause.2 Having used estrogen replacement at any time in the past allowed the blood vessels to respond better to estrogen given at the time of the study. After 5-8 years without estrogen, the coronary and carotid arteries (the blood vessels that supply blood to the heart and brain) thicken, and at the same time the LDL (bad cholesterol) levels start to rise.
What we’ve learned from the scientific research over the past 20 years is that women who are within 10 years of menopause can receive multiple cardiovascular benefits from estrogen but that women more than 10 years past menopause are not ideal candidates to start hormone therapy. Like a night watchman, estrogen can do its job best if there’s never been a time when it wasn’t there, but if you’re within The Estrogen Window, there’s still considerable benefits to be considered from taking HRT.
- Hodis HN, Mack WJ, Henderson VW, et al. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med 2016;374(13):1221–31.
- Vitale C, Mercuro G, Cerquetani E, et al. Time since menopause influences the acute and chronic effect of estrogens on endothelial function. Arterioscler Thromb Vasc Biol 2008;28(2):348–52.