Conference Coverage

Early estrogen loss increases cardiovascular risk in women



The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.

”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.

Dr. Chrisandra L. Shufelt is chair of the division of general internal medicine and associate director of the Women's Health Research Center at Mayo Clinic in Jacksonville, Fla.

Dr. Chrisandra L. Shufelt

Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.

First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.

“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”

Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.

In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.

Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.


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