Editorial

Menopausal vasomotor symptoms: symptom or signal?

Future studies will need to disentangle the complex relationships between vasomotor symptoms, CVD risk and HT use.

A menopausal woman often tells her doctor that she is suffering from vasomotor symptoms, but it is far less often that her doctor wonders whether these symptoms represent anything more than a quality of life issue.

Yet emerging evidence raises questions about whether vasomotor symptoms are more than just a nuisance. Some have hypothesized that the peripheral vasomotor instability typical of hot flashes may herald underlying abnormalities in systemic vascular function. Since hot flashes occur in the vast majority of women during the menopausal transition, there has been increasing interest in elucidating whether or not the presence of vasomotor symptoms may have health implications beyond their impact on a woman’s quality of life.

Emily D. Szmuilowicz
Emily D. Szmuilowicz, MD

A growing body of literature suggests that cardiovascular disease risk factors may differ in women with vs. without vasomotor symptoms. On the one hand, some traditional CVD risk factors may predispose women to vasomotor symptoms.

Women who smoke are more likely to experience hot flashes, and obesity has been postulated to increase the risk of hot flashes through impaired heat dissipation (in spite of the classic association of obesity with increased peripheral conversion of androgens to estrogens in fat tissue). On the other hand, several recent studies suggest that the converse may be true as well. That is, vasomotor symptoms may be independently associated with an adverse CV risk profile as assessed by surrogate CVD risk markers. A number of small studies have reported increased ambulatory blood pressure in women with self-reported vasomotor symptoms. A large observational study from the Netherlands showed higher systolic and diastolic BP as well as cholesterol levels in perimenopausal women with vasomotor symptoms compared to their counterparts without, even after controlling for relevant confounders. An analysis of data from the Study of Women’s Health Across the Nation (SWAN) showed that hot flashes were associated with an increased risk of subclinical CVD (impaired endothelial function and increased aortic calcification), independent of CV risk factors. Furthermore, in a post hoc analysis of the Women’s Health Initiative Hormone Therapy clinical trials, the increased CVD risk with hormone therapy observed with increasing time since menopause was largely noted among the women who reported moderate or severe vasomotor symptoms.

These associations between vasomotor symptoms and increased CVD risk raise interesting questions about whether these symptoms may signal an underlying predisposition towards systemic vascular dysfunction beyond the peripheral vasomotor instability characteristic of hot flashes. Yet the studies published to date do not shed light on whether the presence of vasomotor symptoms is associated with an increased risk of clinical CVD events. Further, as one cannot be randomized to vasomotor symptoms, the observational nature of all of these studies leaves many unanswered questions about the degree to which residual confounding may cloud these associations.

Similarly, the intricate relationships between vasomotor symptoms and HT use, which is now well-known to impact CVD risk, complicate interpretation of these findings. Future studies will need to disentangle the complex relationships between vasomotor symptoms, CVD risk and HT use. As vasomotor symptoms occur in the majority of perimenopausal women, as well as in a substantial minority of older postmenopausal women, these studies will be awaited with interest. Until then, we are left wondering whether hot flashes are a just a symptom or also a signal of something bigger.

Emily D. Szmuilowicz, MD, is an Instructor of Clinical Medicine at Northwestern University and a member of the Endocrine Today Editorial Board.

For more information:
  • Gast GC, Grobbee DE, Pop VJM, et al. Menopausal complaints are associated with cardiovascular risk factors. Hypertension. 2008;51:1492-1498.
  • Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477.
  • Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, et al. Hot flashes and subclinical cardiovascular disease. Findings from the Study of Women’s Health Across the Nation Heart Study. Circulation. 2008;18:1234-1240.

A menopausal woman often tells her doctor that she is suffering from vasomotor symptoms, but it is far less often that her doctor wonders whether these symptoms represent anything more than a quality of life issue.

Yet emerging evidence raises questions about whether vasomotor symptoms are more than just a nuisance. Some have hypothesized that the peripheral vasomotor instability typical of hot flashes may herald underlying abnormalities in systemic vascular function. Since hot flashes occur in the vast majority of women during the menopausal transition, there has been increasing interest in elucidating whether or not the presence of vasomotor symptoms may have health implications beyond their impact on a woman’s quality of life.

Emily D. Szmuilowicz
Emily D. Szmuilowicz, MD

A growing body of literature suggests that cardiovascular disease risk factors may differ in women with vs. without vasomotor symptoms. On the one hand, some traditional CVD risk factors may predispose women to vasomotor symptoms.

Women who smoke are more likely to experience hot flashes, and obesity has been postulated to increase the risk of hot flashes through impaired heat dissipation (in spite of the classic association of obesity with increased peripheral conversion of androgens to estrogens in fat tissue). On the other hand, several recent studies suggest that the converse may be true as well. That is, vasomotor symptoms may be independently associated with an adverse CV risk profile as assessed by surrogate CVD risk markers. A number of small studies have reported increased ambulatory blood pressure in women with self-reported vasomotor symptoms. A large observational study from the Netherlands showed higher systolic and diastolic BP as well as cholesterol levels in perimenopausal women with vasomotor symptoms compared to their counterparts without, even after controlling for relevant confounders. An analysis of data from the Study of Women’s Health Across the Nation (SWAN) showed that hot flashes were associated with an increased risk of subclinical CVD (impaired endothelial function and increased aortic calcification), independent of CV risk factors. Furthermore, in a post hoc analysis of the Women’s Health Initiative Hormone Therapy clinical trials, the increased CVD risk with hormone therapy observed with increasing time since menopause was largely noted among the women who reported moderate or severe vasomotor symptoms.

These associations between vasomotor symptoms and increased CVD risk raise interesting questions about whether these symptoms may signal an underlying predisposition towards systemic vascular dysfunction beyond the peripheral vasomotor instability characteristic of hot flashes. Yet the studies published to date do not shed light on whether the presence of vasomotor symptoms is associated with an increased risk of clinical CVD events. Further, as one cannot be randomized to vasomotor symptoms, the observational nature of all of these studies leaves many unanswered questions about the degree to which residual confounding may cloud these associations.

Similarly, the intricate relationships between vasomotor symptoms and HT use, which is now well-known to impact CVD risk, complicate interpretation of these findings. Future studies will need to disentangle the complex relationships between vasomotor symptoms, CVD risk and HT use. As vasomotor symptoms occur in the majority of perimenopausal women, as well as in a substantial minority of older postmenopausal women, these studies will be awaited with interest. Until then, we are left wondering whether hot flashes are a just a symptom or also a signal of something bigger.

Emily D. Szmuilowicz, MD, is an Instructor of Clinical Medicine at Northwestern University and a member of the Endocrine Today Editorial Board.

For more information:
  • Gast GC, Grobbee DE, Pop VJM, et al. Menopausal complaints are associated with cardiovascular risk factors. Hypertension. 2008;51:1492-1498.
  • Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477.
  • Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, et al. Hot flashes and subclinical cardiovascular disease. Findings from the Study of Women’s Health Across the Nation Heart Study. Circulation. 2008;18:1234-1240.