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September 13, 2022
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Assess CVD risk when considering hormone therapy for menopause symptoms

Fact checked byRichard Smith
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RANCHO PALOS VERDES, Calif. — Menopausal hormone therapy can help alleviate severe vasomotor symptoms, but cardiologists should assess CV risk and consider several other factors when evaluating these patients, according to a speaker.

Perspective from Carl J. Pepine, MD, MACC

Approximately 40% of a woman’s life is spent in menopause, and the average age of menopause onset is 51 years, Shaista Malik, MD, PhD, MPH, FACC, associate vice chancellor of integrative health at the Susan and Henry Samueli College of Health Sciences at the University of California, Irvine, said during a presentation at the Cardiometabolic Health Congress (CMHC) Women’s Cardiometabolic Health and Wellness Masterclass. Many women experience severe menopause symptoms that affect their quality of life, develop unfavorable biomarkers such as insulin and lipids and report unpleasant physical effects, Malik said.

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Source: Adobe Stock

“Menopause is associated with cardiometabolic dysfunction, we now, in 2022, know this,” Malik said during a presentation. “It is more than just biologic aging. But that dysfunction starts several years prior to that last menstrual period. As in many things, we are coming to this late with an understanding of what is going on. Perhaps some of that estrogen therapy could be initiated earlier. But it must be personalized, looking at things like estrogen metabolites. Most women with severe menopausal symptoms should be evaluated for underlying CV risk, and have their lipids measured.”

Connection between menopausal symptoms, CV risk

The most commonly reported menopausal symptom is vasomotor symptoms, often called hot flashes, which affect up to 80% of menopausal women, Malik said.

“We used to think [vasomotor symptoms] only affected quality of life,” Malik said. “It turns out that they are also associated with higher carotid intima-media thickness and lower bone mineral density. They are also associated with atherogenic lipid markers and with inflammation suggesting higher vascular risk.”

Flow-mediated dilation is also lower in early menopause compared with age-matched nonmenopausal women, Malik said, noting symptom severity is similarly related to endothelial dysfunction.

To manage menopausal symptoms, initial observational studies suggested menopausal hormone therapy (HT) was beneficial for both primary and secondary prevention of CHD, Malik said. However, this has not been confirmed in large trials.

In the landmark Women’s Health Initiative study, researchers evaluated two hormone formulations: conjugated equine estrogen (CEE) and CEE combined with medroxyprogesterone acetate for women aged 50 to 59 years. The researchers found that with combination therapy, there was increased risk for CHD, stroke, venous thromboembolism and breast cancer but a decrease in all-cause death, diabetes and other cancers. In the CEE arm, there was increased risk for VTE.

“There was some confusion about the Women’s Health Initiative and why are women still on HT,” Malik said. “It turns out there is nuance to this. And the nuance is there is a timing hypothesis. Evidence shows that if a woman was initiated on the HT within 10 years of menopause and was less than age 60 years, you can see the absolute risk for CHD, stroke, thrombosis and breast cancer and death are all in the protective direction. As you increase in age and time away from menopause onset, those effects start to reverse, particularly for stroke.”

A balanced approach

Malik said clinicians should use a “balanced approach” that individualizes patient risks and benefits with respect to menopausal HT.

“The benefit of HT is it is the most effective for vasomotor symptoms, which are linked to CV outcomes,” Malik said. “There is a decreased event rate, particularly in those women who are recently menopausal, though there are risks for venous thromboembolism and stroke.”

Emerging research suggests there is a lot of genetic variability in estrogen metabolism; some women have a harder time clearing estrogen metabolites, Malik said. For these women, complementary therapies such as supplements that can enhance hepatic clearance of these metabolites may have a beneficial effect.

Menopausal HT should be avoided for anyone with 10-year atherosclerotic CVD risk of 7.5% or more, Malik said, noting that recommendations do not support HT for controlling CV risk factors. Guidance does not recommend the use of bioidentical hormones, which are not FDA regulated.

“Many [cardiologists] do not initiate HT; however, we may see patients who are prescribed HT,” Malik said. “There needs to be some caution in those that have moderate risk. If they do have low risk and are in that 10-year window, it is acceptable for them to be on HT.”

Most important, Malik said, is that cardiologists be alert for menopausal symptoms before menopause.

“Look at [follicle-stimulating hormone] levels, which start to increase before estrogen levels decrease,” Malik said. “When a woman says she is having issues with weight gain, it is time to use the American Heart Association’s Life’s Simple 7 and [recommend] lifestyle. It still works. Our patients with these symptoms need our support because they do not always get it.”

In an updated position statement from the North American Menopause Society published in July and reported by Healio, the organization stated menopausal HT remains the most effective treatment for vasomotor symptoms and genitourinary syndrome of menopause, saying the benefits outweigh the risks for most healthy women younger than 60 years and within 10 years of menopause onset. The position statement also emphasized personalized treatment, with a periodic reevaluation to analyze each individual’s benefit-risk profile.