Menopausal Hormone Therapy (HT)

 

In 2002, the Women’s Health Initiative (WHI) hormone study, which was funded by the National Institutes of Health, was halted after six years. Because the risks which hormone therapy (HT) appeared to exceed the benefits, many people concluded that previous observational studies, such as the Nurses Health Study, Framingham Study and others, which indicated that HT was beneficial, were incorrect. The previously demonstrated benefits included a risk reduction of heart attacks, bone fractures due to osteoporosis, Alzheimer’s disease and deaths from all causes. As a result, many women stopped taking HT and decided to suffer the consequences.

 

Now, we are asking if these fears of the risks of HT are well substantiated. When one compares the WHI and previous studies, one fact is evident: women in the observational studies in which estrogen was protective began taking estrogen during or shortly after the beginning of menopause for hot flashes and other symptoms. Women in the WHI study were an average of 63 years old, about 12 years past menopause, and, with rare exceptions, without symptoms. Also, approximately 20% of the women were 70 to 79 years of age. Other studies have shown that hardening of the arteries or atherosclerosis, the process that leads to heart attacks and strokes, accelerates after menopause. In fact, the rates of heart attack in women reached the same level as men by 10 to 15 years after menopause.

 

Estrogen is thought to have a protective effect against atherosclerosis (plaque in the arteries) by decreasing the level of “bad” LDL cholesterol and increasing “good” HDL cholesterol. It also could accelerate the onset of heart attacks in women who already have patches of advanced atherosclerosis in their arteries. Therefore, the affect of estrogen is positive when used early and harmful when used late. Thus the WHI study may not have been a primary prevention study, since too many of the women already had pre-existing but silent atherosclerosis.

 

 

Are these fears of the risks of HT well substantiated?

 

When one compares the WHI and older studies, one fact is evident: Women in the older observational studies in which estrogen was protective, began taking estrogen during or very soon after the menopause for hot flashes and other estrogen deficiency symptoms. Women in the WHI study were an average of 63 years old, about 12 years past menopause, and, with rare exceptions, without menopausal symptoms.

 

Other studies have shown that hardening of the arteries, or atherosclerosis, the process that eventually leads to heart attacks and strokes, accelerates after menopause. In fact, rates of heart attack in women catch up with those in men by 10 to 15 years after menopause. Estrogen is thought to have a protective effect against atherosclerosis by decreasing the level of “bad” LDL cholesterol and increasing “good” HDL cholesterol. It also could accelerate the onset of heart attacks in women who already have patches of advanced atherosclerosis in their arteries.

 

Therefore, the affect of estrogen is positive when used early and deleterious when used late. Thus the WHI study may not have been a primary prevention study after all since too many of the women already had preexisting but silent atherosclerosis.

KEEPS is designed to test this theory by recruiting 720 healthy, recently menopausal women for a randomized, placebo-controlled, double-blinded trial of HT for four years.