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“Window of Opportunity” Theory for Menopausal Hormone Therapy Explained

By Jannet Huang, MD, FRCPC, FACE, ABHM

I have had many patients who ask me why I am a “pro-hormone” doctor. I am going to use this article to explain why I support the use of menopausal hormone therapy.

A simple way to look at the effect of estrogen is that estrogen is a good “preserver”, but estrogen is not a good “repairer”. When a woman starts estrogen therapy early, ie. before cessation of her menstrual periods, or shortly thereafter (probably within 5yrs), estrogen can help her maintain function. However, when a woman starts hormone therapy late, estrogen is no longer able to provide preventative benefits, and it may actually cause harm.

Many women were scared by the WHI (Women’s Health Initiative Study) which allegedly showed hormone therapy to cause more heart attacks and strokes in women. Many women stopped their own hormone therapy, and many others who might have benefited from hormone therapy were too scared to start. It is important to realize that the average age of women who participated in WHI was 63. These women were on average 10-20 years beyond their last menstrual period when they were started on hormone therapy! The memory sub-study involved women aged 70-79 at the outset of the study! It made sense that this study did not show any protective benefit of estrogen therapy on dementia. Starting hormone therapy at age 70-79 is much too late for prevention of cognitive decline. The damage in the brain leading to dementia would have been well on its way by then.

In my opinion, the only unarguable risk of oral estrogen is increased risk of blood clotting. Now let’s take a look at the increase in stroke and heart attacks in WHI. In the 10-20 years beyond menopause, plaque would have already been forming in the arteries. If you then start oral estrogen (Premarin — from pregnant mares’ urine, the estrogen taken orally in WHI) which increases the risk of blood clotting, it made sense that these women in WHI had more heart attacks and strokes. The goal should be to prevent the formation of plaque in the arteries in the first place!

Even the WHI yielded data in support of the “window of opportunity” theory. 10% of the over 16000 women who participated in WHI were between age 50-59. In this group of women, there was actually less plaque in their coronary arteries (as measured by coronary artery calcium scores) compared to the women who did not take hormone therapy (control group). The idea here is to start estrogen before the arterial plaque formation accelerates after menopause.

With respect to the brain, there seems to be a dichotomous reaction to estrogen. When you place healthy neurons in a petri-dish, the presence of estrogen protects the neurons from injury. On the other hand, if you have neurons that are already damaged, the addition of estrogen actually increased cell death when these damaged neurons were exposed to an insult. This phenomenon was also seen in an animal model of stroke. Estrogen given to the rodents prior to their experimentally-induced stroke protected their brains from damage.

An indirect piece of evidence that estrogen is actually protective against cardiovascular disease and cognitive decline comes from the data in women who had their ovaries removed during their hysterectomy compared to the women who kept their ovaries with their hysterectomy for benign disease (eg. fibroids). The women who had their ovaries removed with their hysterectomy had increased risk of heart attacks, stroke, cognitive decline, Parkinson’s disease and lung cancer. This increase in risk was more significant the young the woman were when they had their ovaries removed. Moreover, this increased risk was ameliorated if these women were placed on estrogen therapy at the time when their ovaries were removed.

In 2002 when the WHI results were first publicized (and hormone therapy was given a foul name), many women were scared and took themselves off their own hormone therapy, or their physicians told them to get off hormone therapy. Some of these women had been on hormone therapy for more than 30 or 40years. If they were not doing well on hormone therapy, they would not have stayed on for so long! Many of these women got into trouble after they stopped their hormones — they experienced hot flashes, sleep and mood disturbance, loss of sense of well-being, hip fractures and even heart attacks. These women were putting themselves through menopause all over again! I believe that ultimately we need to listen to the individual woman’s body. A woman “declares” herself as someone who does or does not do well on estrogen quite early on when they try hormone therapy. If a woman feels well on hormone therapy with benefits on their overall sense of wellbeing, sleep, sexuality etc, her body is telling us she needs the estrogen. If a woman gets side effects and does not feel well on hormone therapy, hormone therapy would not be appropriate for her.

My conclusion is estrogen therapy should be started in the “right” women within the “appropriate time window”. It is not a “black and white” situation. Menopausal hormone therapy is not “all good” or “all bad”. The bottom line is that each woman needs to evaluate her own needs and her own risk factors so she can make her own individual decision.

~By Jannet Huang, MD, FRCPC, FACE, ABHM
October 2009