Back in 2002 and 2004, the Women’s Health Initiative Study (WHI) suggested that there was a slight increased risk of cardiovascular events in women on synthetic hormone replacement drugs. The drugs in question were Premarin, which is a horse-based estrogen, and Provera, which is a synthetic form of progesterone and not a hormone at all.
The results of the study (https://www.nhlbi.nih.gov/whi/) garnered a great deal of media attention and led to a substantial drop in the use of hormone replacement therapy for women in menopause. But that research was flawed.
Let’s take a brief look at the history.
The PEPI (Postmenopausal Estrogen and Progestin Intervention) study published in the 1990s found that women who take estrogen and progesterone (synthetic progestin) at menopause had cardiac protection and a subsequent reduction in cardiac risk. (Source: Maturitas, July 1997; 27(3):261-74.)
Because of these results showing that hormone replacement therapy started at menopause gives cardiac protection, investigators sought to determine if starting it in women well into menopause (an average of 15 years and at age 67) with potential for heart disease would be protective.
Unlike the PEPI study, they found no such protection. At this point hormone placement therapy did not protect, nor did it cause, heart disease.
(Sources: Hulley S, Grady D, Bush T, et al., “Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women: Heart and Estrogen/Progestin Replacement Study (HERS) Research Group”; Journal of the American Medical Association, 1998; 280:605-613; Grady D, Herrington D, Bittner V, et al., “Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II)”; JAMA, 2002; 288:49-57.)
Then came the Women’s Health Initiative Trial to evaluate the health risks, or protection, associated with hormone replacement therapy. But unlike conventional medicine where hormone placement therapy is started at the onset of menopause, they started it at any age, with the average woman being more than 10 years into menopause. It showed a slight increased risk of cardiovascular disease.
When researchers looked further, they found that women who had started hormone replacement therapy 10 years or less into menopause actually had a 40 percent reduction in cardiovascular events and disease. There was some potential for risk only when the synthetic hormones were started late or well into menopause.
A study published in the New England Journal of Medicine evaluated hundreds of women for five years, using ultrasound to measure changes in the cardiovascular system.
They found that if estrogen was started within six years of menopause, it led to a reduction in the progression of atherosclerosis. There was no such benefit if estrogen was started 10 years or later after the onset of menopause. (Source: New England Journal of Medicine, March 31, 2016; 374;13 nejm.org.)
A Danish study followed for 16 years more than 2,000 women who were put on hormone replacement therapy at the onset of menopause. The women were randomly selected to receive hormone replacement therapy or no treatment.
Unlike the studies in the United States, this European study used actual estradiol (human estrogen) rather than horse estrogen, and the use synthetic progestin drugs.
In this long-term study, there was no increased risk of cardiovascular deaths or disease in women on hormone replacement therapy. In fact, the women on long-term hormone replacement therapy were 40 percent less likely to die, and about 75 percent less likely to have a cardiovascular event.
This study has shown once again that hormone replacement therapy, when resembling human hormones as closely as possible, does not cause disease — but in fact substantially reduces the risk of cardiovascular disease and death. (Source: BMJ, 2012; 345:e6409 doi:10.1136/bmj.e6409.)
Studies have also shown that not only estrogen is cardioprotective. Testosterone levels are associated with the development of cardiovascular risk and disease in women. Testosterone is a more accurate predictor of subsequent cardiovascular disease than cholesterol. (Source: Journal of Clinical Endocrinology & Metabolism, July 2014; 99(7):E1287–E1293.)
Other studies have shown that the addition of testosterone is synergistic (interacts) with estrogen and protects against atherosclerosis in women. (Source: Archives of Medical Research 46 (2015); 619e629.)
Hormone replacement therapy is an option for women.
There’s been a lot of fear and misinformation regarding hormone replacement therapy in menopause and perimenopause, and that stemmed from a very limited number of clinical studies using synthetic drug hormones in an unusual fashion. In the study that showed risk, these drugs are started several years into menopause. But the typical practice is to start hormones, even synthetic hormones, at the onset of menopause. Then those risks not only go away, they substantially diminish. Hormone replacement therapy protects the heart.
For cardiovascular protection, the ideal hormone replacement therapy for a woman in menopause involves replacing the hormones in a fashion that mimics what her ovaries did before menopause.
Testosterone is a dominant hormone in a young healthy woman, and estrogen is present in about one-tenth to one-twentieth the concentration. So, we replaced testosterone and estrogen in the form of a tiny pellet (the size of a grain of rice) that is inserted under the skin and breaks down over about three months. In addition, progesterone — the actual hormone, not the synthetic drug – is taken orally each night.
To learn more about how hormone replacement therapy can protect your heart, call us at 586-992-8300 to schedule an appointment.
Dr. Charles Mok