Hormone Therapy & Heart Disease – KEEPS Study Report
Sometimes it seems the older you get, the more your body becomes like a giant chemistry experiment. You tweak one thing to feel better, upsetting the apple cart and leading to other issues. This is never more true than during the menopausal transition, when your hormones careen around the roller coaster track while you hang on for dear life, wondering when the crazy ride will bring you back to the safety of the ride’s platform.
When you’ve hot flashed, suffered from never-ending insomnia and yelled at your kids for the umpteenth time, deciding to give hormone therapy (HT) a try seems logical and necessary: if for nothing else than to save your sanity.
The problem is—many of you know that heart disease is the number-one killer of women in the U.S. and that might have you wondering what impact HT will have on your own cardiovascular health.
Turns out, it’s a matter of plain old timing.
Put Your Heart Into It
In 2010, the National Institute of Health released results of a 15-year study called the Women’s Health Initiative, which addressed cardiovascular disease, osteoporosis and cancer as it relates to menopausal women on hormone therapy or HT.
That study discovered that replacement hormones might elevate the risks of stroke and heart attack in older women. However, most of the study’s participants were long past the start of menopause, or their last period. Why is that important? Because conversely, women who go on HT within four years after their last period do not generally suffer negative effects on their cardiovascular system, according by Dr. S. Mitchell Harman, director of the Kronos Longevity Research Institute. He was the lead investigator for the KEEPS (Kronos Early Estrogen Prevention Study) that examined whether starting HT sooner after the onset of menopause reduces the risks of cardiovascular disease and also whether there is a difference between oral and transdermal application of the hormones.
Dr. Harman discovered:
- Neither transdermal nor oral estrogen treatment significantly accelerates or decelerates rate of change of carotid artery intimal medial thickness (CIMT) in healthy recently menopausal women.
- Both estrogen treatments have some potentially beneficial effects on markers of CVD risk, but these differ depending on the route of estrogen delivery with improvements in LDL and HDL cholesterol seen with oral and reduced insulin resistance with transdermal.
- No significant effects were observed on rate of accumulation of coronary artery calcium.
- Women reported significant relief of vasomotor hot flash symptoms with either form of estrogen
Dr. Harman stated post-study that, “Four years of estrogen treatment in healthy recently menopausal women is unlikely to worsen risk of cardiovascular events and is therefore a relatively safe strategy for relief of menopausal symptoms.”
Different Points of View
Dr. Joseph Raffaele, formerly a clinical assistant professor of medicine at Dartmouth Medical School and co-founder of the PhysioAge Medical Group, believes KEEPS is a good start, but that much more research is in order. He points out that just a tiny percentage of the women in the study had any significant coronary calcium at all: 85% of the women had a coronary calcium score of ‘zero.’ The 15% who did have calcium buildup showed an improvement with both the estrogen and estradiol treatments.
“The problem with the WHI study was that its 16,000 subjects were on average too old and too unhealthy to provide meaningful answers to women considering hormone replacement as they enter menopause,” says Dr. Raffaele in a recent blog.
“The problem with KEEPS was the opposite: its subjects were on the whole too young and too healthy (to show significant improvement), especially for a study that only lasted four years. The researchers should have either used a broader cross-section of subjects or made the study much longer to measure how hormone replacement affects measures of atherosclerosis.”
“KEEPS was not worthless,” says Dr. Raffaele, “The news of the announcement focused on the positives: that hormone replacement safely improves menopausal symptoms including hot flashes and night sweats, depression, diminished libido and bone density.”
“That’s reassuring to women and should help continue to reverse the decade-long misinterpretation of the WHI data that led many physicians to advise against HRT.”
However, Dr. Raffaele says additional research should include a base of at least 5,000 subjects of varying ages and baseline cardiovascular health, and that those women should be followed for 10 years.
This opinion is echoed by Dr. Josh Trutt who says, “In the WHI trial, the women were NOT recently menopausal and were at relatively higher cardiovascular risk: on average 62.5 years old and either overweight or with high blood pressure. The women in KEEPS are a decade younger and overall healthier, and on estrogen for a shorter time period. It would have taken a very powerful effect to show a benefit in this group.”
Dr. Raffaele points out that just a week after being disappointed by the KEEPS trial report, a new Danish study demonstrated very positive results for recently menopausal women who went on long term HT. The study appeared in the British Medical Journal. He further explained that in healthy women (such as KEEPS studied) you need to follow them for a longer period of time to show benefit. The Danish study followed them for over ten years. This is key to answering the question KEEPS couldn’t answer: Does taking HT in early menopause decrease the likelihood of developing cardiovascular disease? The answer is a resounding ‘yes.’ These Danish women had over a 50 percent reduction in combined heart attacks, heart failure and death. Remarkably this reduction started to accrue very soon after initiation of therapy. The cardiovascular benefit occurred without any increase in cancers of any type, including breast cancer for which there was a non-significant reduction in comparison to placebo. Nor was there a significant increase in blood clots or pulmonary emboli.”
However, Dr. Raffaele does point out that the study used 2 mg of oral estradiol, a relatively high dose, and a progestin that is not commonly used in the US for HT. This study didn’t compare different types of estrogens or routes of delivery: for example, whether transdermal estradiol instead of oral, or micronized progesterone instead of norethisterone acetate, would have had better or worse effects on cardiovascular disease or cancer.
After My Own Heart…
Where does that leave you? Consider your options; discuss HT with your menopause specialist taking into account your own personal health background. This will help you and your specialist weigh the risks and benefits to fit your personal needs.
With a family history of heart disease, I went on bioidentical HT early in my menopausal journey. It relieved my brain fog, sleeplessness, hot flashes, vaginal dryness and crashing libido! All the numbers in my Lipid Panel remain in the normal range and my calcium deposit score remains at 0, and my bone mineral density is all in the normal range. HT gave me my quality of life back and put a smile on my face. In my “heart”, I know this was the correct course of action for me!
Suffering in Silence is Out! Reaching Out is In!