By Seema Gupta, MD, MSPH

Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV

Dr. Gupta reports no financial relationships relevant to this field of study.

SYNOPSIS: Women 42-55 years of age who experience hot flashes are more likely to exhibit poor vascular function.

SOURCE: Thurston RC, Chang Y, Barinas-Mitchell E, et al. Physiologically assessed hot flashes and endothelial function among midlife women. Menopause 2017 Jun 19. doi: 10.1097/GME.0000000000000857. [Epub ahead of print].

Vasomotor symptoms (VMS), often referred to commonly as hot flashes and night sweats, are considered by clinicians to be the telltale signs of menopause. In the United States, 75-80% of menopausal women report hot flashes. For about one-third of this group, the reported episodes are described as severe or frequent.1 Additionally, new data indicate that hot flashes often start earlier than once believed and can persist for a decade or even longer.2 Although hot flashes can affect quality of life negatively, they may be an indication of emerging vascular dysfunction that can lead to cardiovascular disease (CVD), which is the leading cause of death among women. A fair amount of research has connected menopause with CVD, including several risk factors. A decline in the ovarian estrogen estradiol (E2) may be a factor in CVD increase among post-menopausal women.

Emerging data demonstrate that women with early menopause (42-55 years of age) may exhibit an impairment of endothelial function in the early menopausal years, wherein the carotid intima-media thickness is not yet affected, linking the menopausal symptom of hot flashes to markers of poorer endothelial function.3 Thus, this endothelial injury and dysfunction may be an initiating event in atherosclerosis development among early midlife women.

By evaluating data from 272 nonsmoking women 40-60 years of age reporting either daily hot flashes or no hot flashes and free of clinical cardiovascular disease, Thurston et al tested whether physiologically assessed hot flashes were associated with poorer endothelial function. The study excluded women with neoplasia, hysterectomy and/or bilateral oophorectomy, kidney failure, seizures, Parkinson’s disease, Raynaud’s phenomenon, or current pregnancy. The researchers also excluded women with a history of recent use of reproductive hormone agents, serotonin reuptake inhibitors, insulin, or cardiovascular drugs.

All women underwent physical examinations, brachial artery flow-mediated dilation (FMD) to assess endothelial function, carotid artery ultrasound, blood draw, and ambulatory hot flash monitoring using an electronic hot flash diary, a wrist actigraph, and a physiologic hot flash monitor. Menopause status was assessed from reported menstrual bleeding patterns. Estradiol levels, glucose, high-density lipoprotein cholesterol, triglycerides, total cholesterol, insulin, C-reactive protein, and interleukin-6 were evaluated.

On average, study participants were 54 years of age, white, college educated, postmenopausal, and demonstrated a relatively favorable CVD risk factor profile. Researchers found that even after controlling for other CVD risk factors, younger women (40-53 years of age) who experienced hot flashes (beta [standard error] = -2.07 [0.79]; P = 0.01) and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05]; P = 0.03, multivariable) were associated with lower FMD compared to women who did not experience hot flashes, indicating poorer endothelial function. These associations could not be accounted for by estradiol changes and were not observed among the older women (54-60 years of age).

COMMENTARY

While hot flashes, one of the most common symptoms of menopause, interfere with a woman’s overall quality of life, Thurston et al demonstrated that these frequent hot flashes also may signal emerging vascular dysfunction that can lead to CVD, particularly for younger midlife women (40-53 years of age).

The finding that both the reported presence of hot flashes and more frequent physiologically assessed hot flashes were associated with lower flow-mediated dilation among younger midlife women independent of estradiol indicates that impairment in endothelial function may be an initiating event in the atherosclerotic process. Frequent hot flashes may mark emerging vascular dysfunction. Interestingly, associations between hot flashes and FMD were not observed among the older women in the sample.

The important findings of this research point to the potential role of not only hormones, but also hot flashes, in the cardiovascular changes that occur in women undergoing early menopause and highlight the potential role that the endothelium may play in the physiology of early hot flashes and CVD initiation.

Although this work needs further validation, the findings may be an early signal that among early midlife women, frequent hot flashes may herald an emerging vascular dysfunction. Therefore, it is critical that this subgroup not only is treated for hot flashes as a symptom but also be screened more closely for CVD risk factors.

REFERENCES

  1. Williams RE, Kalilani L, DiBenedetti DB, et al. Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States. Climacteric 2008;11:32-43.
  2. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015;175:531-539.
  3. Bechlioulis A, Kalantaridou SN, Naka KK, et al. Endothelial function, but not carotid intima-media thickness, is affected early in menopause and is associated with severity of hot flushes. J Clin Endocrinol Metab 2010;95:1199-1206.