Arresting news: Hot Flashes and the Heart

If all the news you followed in the last ten years was your Facebook feed, you probably missed the biggest thing ever to happen in women’s health: the Women’s Health Initiative (WHI). The WHI was a group of clinical trials investigating disease from women’s perspective, righting the wrongs of most other trials, which have vastly underrepresented women in their patient populations.  One of the most catastrophic of the studies for some pharmaceutical companies was one on hormone therapy (HT) use for menopausal symptoms (hot flashes, night sweats, mood swings...if these don’t ring a bell, ask your mother). The study looked at HT use and the risk for breast cancer and cardiovascular disease (which includes heart attacks, strokes and blood clots, among others). The 16,000-plus women recruited to the trial were healthy and postmenopausal, half of whom received HT and half of whom received a placebo. Women were contacted every 6 months to report their health status and each participant had a mammogram and clinical breast exam every year. The trial was designed to continue for 8.5 years, but was stopped after 5.  Why? HT caused more breast cancer, more blood clots in the legs, more strokes and more heart attacks than placebo. (1)

Before the WHI, around 1 in every 4 menopausal women was taking some form of HT.  Thanks to the WHI, only 5 women in 100 are now willing to take the risk. (2) Although hot flashes are an annoying symptom that won’t kill you outright (though you might want to kill others), recent research is suggesting that the flashes themselves may be a marker of increased cardiovascular risk, just like high cholesterol or high blood sugar. Because cardiovascular disease is the leading cause of death among women in the United States, identifying treatable risk factors is critical.

The WHI addressed this issue, too. The leading researchers for the WHI looked more closely at the subgroup of women who had moderate to severe hot flashes and night sweats.  The team found that during the first year of treatment, symptomatic women had a significantly increased risk for coronary heart disease when compared to women with fewer to no such symptoms. In addition, the risk of stroke was significantly elevated. (3)

With the WHI behind us, we now have three new studies of profound scientific integrity supporting a link between the symptoms of menopause and the risk factors or evidence of CVD.  The other three are:

1.     The Eindhoven Perimenopausal Osteoporosis Study, which showed that women with hot flashes and night sweats had higher cholesterol, a higher body mass index (BMI), and higher blood pressure than women without symptoms. (4)

2.     The Heart section of the Study of Women Across the Nation (SWAN), in which women with moderate to severe hot flashes were shown to have more cholesterol buildup in their aorta (a huge central blood vessel giving off all of the branches to the rest of the body).  Other blood vessels (they tested a big one in the arm) had a harder time opening to allow more blood flow. (5)

3.     A study by Dr. Rebecca Thurston (in the photo with me), who wanted to better understand the reasons behind the hot flash-CVD link. She found that the parasympathetic nervous system (part of the larger autonomic nervous system which regulates unconscious actions like heartbeats and breathing) doesn’t work as well during a hot flash. Most people are familiar with the sympathetic nervous system function that controls the body’s “fight or flight” response. In contrast, the resting heart rate is generally governed by the parasympathetic nervous system. Epidemiological studies have shown that the resting heart rate, which is also a measure of vagus nerve function, predicts mortality. Simply put, with higher parasympathetic nervous system stimulation there is higher vagus nerve activity which leads to a slower heart rate and ultimately a better cardiac outcome. When women experience hot flashes, their heart is less regulated by the parasympathetic nervous system and this effect is believed to have an untoward effect on the heart rate leading to a worse outcome for cardiovascular disease. (6)

Given the recent studies linking hot flashes to coronary heart disease, it may make sense for you to treat your hot flashes, not only to abate bothersome symptoms but to decrease your risk of cardiovascular disease. Taking hormone therapy to treat those hot flashes paradoxically appears to increase the risk of developing coronary artery disease under certain conditions. So what should perimenopausal and menopausal women do?

There are alternatives to HT.  An interesting new approach is the one presented by estrogen receptor beta "agonists," which stimulate estrogen receptors when your own estrogen levels fall too low. Teams of researchers have shown that these ER-beta agonists may have positive effects on blood vessel function and blood pressure, without the side effects of HT or its increased cancer and cardiovascular risks. (7) No ER-beta agonist has made it across the FDA finish line yet, but certain over-the-counter botanical supplements that contain these compounds are now available on the market and may provide a safer solution to treating menopausal symptoms.

References:

1.     Writing Group for the Women's Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal WomenPrincipal Results From the Women's Health Initiative Randomized Controlled Trial. JAMA. 2002;288(3):321-333.

2.     Brian L. Sprague, PhD, Amy Trentham-Dietz, PhD, and Kathleen A. Cronin, PhD. A Sustained Decline in Postmenopausal Hormone Use: Results From the National Health and Nutrition Examination Survey, 1999–2010. Obstet Gynecol. 2012 September; 120 (3):595-603.

3.     Jacques E. Rossouw, MD; Ross L. Prentice, PhD; JoAnn E. Manson, MD, DrPH; LieLing Wu, MSc; David Barad, MD; Vanessa M. Barnabei, MD, PhD; Marcia Ko, MD; Andrea Z. LaCroix, PhD; Karen L. Margolis, MD; Marcia L. Stefanick, PhD. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause. JAMA. 2007;297(13):1465-1477.

4.     Alison J. Huang, MD, George F. Sawaya, MD, Eric Vittinghoff, PhD, Feng Lin, MS, and Deborah Grady, MD. Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women. Menopause: The Journal of The North American Menopause Society, Vol. 16, No. 4, pp. 639-643.

5.     Gerrie-Cor M. Gast, Diederick E. Grobbee, Victor J.M. Pop, Jules J. Keyzer, Colette J.M. Wijnands-van Gent, Go¨ran N. Samsioe, Peter M. Nilsson, Yvonne T. van der Schouw. Menopausal Complaints Are Associated WithCardiovascular Risk Factors. Hypertension. 2008;51:1492-1498.

6.     Rebecca C. Thurston, PhD, Israel C. Christie, PhD, and Karen A. Matthews, PhD. Hot flashes and cardiac vagal control during women’s daily lives. Menopause: The Journal of The North American Menopause Society, Vol. 19, No. 4, pp. 406-412.

7.     Zhu Y, Bian Z, Lu P, Karas RH, Bao L, Cox D, Hodgin J, Shaul PW, Thoren P, Smithies O, Gustafsson JA, Mendelsohn ME. Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta. Science. 2002 Jan 18;295(5554):505-8.