Increased Number of Menopause Symptoms Tied to Increased Cardiovascular Disease Risk

Matthew Nudy, MD

New research from Penn State Hershey Medical Center details a potential link between the number of menopause symptoms experienced and the risk of cardiovascular disease in women.

Results of the study, which were presented during the 2020 Virtual Annual Meeting of The North American Menopause Society (NAMS), suggest having 2 or more moderate to severe menopause symptoms was linked to an increased risk of cardiovascular disease (CVD). The study also found supplementation with calcium and vitamin D did not diminish the apparent risk observed in the 20,000-woman cohort.

“We found that even severe hot flashes were not associated with any adverse clinical health outcomes when occurring on their own, but if they or any other moderate to severe menopause symptoms were present in combination, there was an association with an increased risk of cardiovascular disease,” said lead investigator Matthew Nudy, MD, an internal medicine specialist, in a statement from the NAMS.

With an interest in the overall impact of vasomotor menopausal symptoms on clinical health outcomes, Nudy and a team of colleagues designed their study with the intent of detailing potential associations between severity and/or number of symptoms in women from the Women’s Health Initiative (WHI)-Calcium and Vitamin D (CaD) trial. Of note, the WHI-CaD trial was a randomized, double-blind, placebo-controlled study assessing the effects of vitamin D and calcium supplementation on incident hip fracture and other clinal outcomes in 36,282 women aged 50-79 years old from the original WHI.

From WHI-CaD, Nudy and team identified a cohort of 20,050 women for inclusion in the current study. Investigators also obtained information related to outcomes of interest including hip fracture, colorectal cancer, invasive breast cancer, all-cause mortality, CaD global index, coronary heart disease, stroke, cardiovascular death, and total CVD—all of which were used as outcomes the current analysis. Of note, CaD global index was defined as a composite end point of hip fracture, colorectal cancer, invasive breast cancer, and all-cause mortality.

Menopausal symptoms of interest for the NAMS 2020 study included hot flashes night sweats, dizziness, heart racing or skipping beats, tremors, feeling restless or fidgety, feeling tired, difficulty concentrating, forgetfulness, mood swings, vaginal dryness, breast tenderness, headache or migraine, and waking up multiple times at night. Severity and incidence of symptoms was recorded in a questionnaire at baseline of the trial.

For the purpose of the analysis, severity of symptoms was defined as none, mild, moderate, or severe. Additionally, patients were classified into groups defined as having no symptoms, 1 symptom, and 2 or more symptoms.

Investigators planned multiple analyses as part of their study. These included use of multivariable Cox proportional hazards regression models to test associations between symptom severity and number of symptoms with health outcomes, an analysis to assess whether calcium and vitamin D supplementation modified any associations, and an exploratory analysis to examine associations between severity of each menopausal symptom and total CVD events.

Results of the investigators’ analyses revealed no associations between severity of hot flashes or night sweats and any of the health outcomes of interest. Results indicated number of menopausal symptoms was significantly associated with risk for stroke (HR, 1.41; 95% CI, 1.04-1.91 for 2 or more symptoms vs. none; HR, 1.19; 95% CI, 0.88-1.61 for 1 symptoms vs. none, P for trend=.02)and total cardiovascular disease (HR, 1.37; 95% CI, 1.20-1.56, for 2 or more symptoms vs none; HR, 1.00; 95% CI, 0.87-1.15 for 1 symptom vs. none; P for trend <.001).

After stratification by randomization status, investigators found no impact from supplementation on any of the aforementioned associations. Results also indicated severities of individual menopausal symptoms, such as night sweats, restless and fidgety, difficulty concentrating, dizziness, heart racing or skipping beats, feeling tired, and forgetfulness were associated with higher total CVD.

This study, “The Severity of Vasomotor Symptoms and Number of Menopausal Symptoms in Postmenopausal Women and Select Clinical Health Outcomes in the Women’s Health Initiative Calcium and Vitamin D Randomized Clinical Trial,” was presented at NAMS 2020.