July 2, 2002: This is the day that will go down in medical history as the day that millions of women turned on the morning news to hear that the estrogen that they took every morning could cause cancer, heart disease, stroke and, ultimately, death. There was a collective national flush as understandably nervous, angry women tossed their hormones down the toilet. Prempro™ prescriptions immediately dropped by 70%.
And here we are 10 years later. Countless women are suffering with hot flashes, vaginal dryness and insomnia with the belief, propagated by the media and many doctors, that they are putting themselves at huge risk if they take hormone therapy.
This belief was based on findings from the Women’s Health Initiative (WHI), a study that enrolled 27,000 women between 50-79 years of age to determine if postmenopausal estrogen therapy would decrease the risk of dying from cardiovascular disease.
Despite earlier studies that suggested otherwise, women in the WHI who used estrogen and progestin had a 28% increase in heart attacks, a 41% increase in stroke, and a 26% increase in breast cancer, and a more than two-fold increase in blood clots. No wonder women were flushing their hormones down the toilet.
Further analysis, however, revealed two significant flaws in the WHI study:
Flaw 1: The majority of the women were not newly menopausal, but were years beyond the onset of menopause. In fact, the average age of the women who participated in WHI was 63 – and 70% of the women were over 60! When the data was later divided by age group, the results in younger women were much more reassuring. We now understand the concept of a critical window. If hormone therapy is started at the onset of menopause, the risks appeared to be much lower.
Flaw 2: All of the women in the WHI were given an oral estrogen. It seems that transdermal estrogens, such as patches, sprays and gels applied to the skin, are safer than estrogen taken by mouth. Among other things, transdermal estrogens are not metabolized by the liver and do not appear to increase the risk of blood clots that lead to stroke, or heart attack.
For many years menopause experts have suspected that the data would have been very different if the study group was younger and used a different estrogen. But in the scientific community, it’s one thing to suspect something – and it’s another thing to prove it.
That’s why those of us keyed into the menopause world have eagerly awaited the results of the Kronos Early Estrogen Prevention Study (KEEPS), presented yesterday at the North American Menopause Society’s annual meeting in Orlando.
I’ll give you the headline first: Estrogen and progestogen therapy started soon after menopause, not only relieve symptoms, but appear safe.
The Kronos Early Estrogen Prevention Study (KEEPS) was a four-year, randomized, double-blinded, placebo-controlled clinical trial (in other words: reliable, scientific and unbiased) of low-dose oral or transdermal estrogen and progesterone in 727 healthy women aged 42-58 who were within 3 years of the onset of menopause.
There were 3 groups:
- Group 1 received oral estrogen (given as Premarin®, 0.45 mg/day – a lower dose than the 0.625 mg/day used in the WHI)
- Group 2 received a transdermal estradiol (given by Climara® patch, 50 µg/day [µg = microgram])
- Group 3 received a placebo (no hormone)
In women who used either oral or transdermal estrogen, there was excellent relief of symptoms. There was no increase in blood pressure, no effects on atherosclerosis, no increase in breast cancer or uterine cancer, or blood clots associated with stroke and myocardial infarction.
Oral estrogen was associated with an increase in HDL (“good”) cholesterol along with a decrease in LDL (“bad”) cholesterol. However, there was an increase in triglyceride levels.
Transdermal estrogen did not affect cholesterol or triglycerides, and lowered insulin resistance.
The bottom line is it appears to be safe for most newly menopausal women to use hormone therapy. While both oral and transdermal estrogen have minimal risks, there appear to be advantages of transdermal estrogen therapy, particularly if a women is diabetic or at risk for cardiovascular disease.
How long can a woman safely continue hormone therapy? No one really knows, but as the study continues, that question will be answered as well.
So, there you have it. The KEEPS study researchers emphasize that hormone therapy must be individualized depending on symptoms, priorities and risk factors. Estrogen isn’t poison and, for the most part, miserable menopausal women can be flash-free and no longer need to feel like they are risking their lives in the name of a good night of sleep. Hallelujah.