Menopausal hormone therapy safe for most women at low CVD risk
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Menopausal hormone therapy for bothersome vasomotor or other symptoms is safe and appropriate for most women at low atherosclerotic CVD risk, whereas a nuanced approach is needed for intermediate-risk women, researchers reported.
“Many cardiologists are reluctant to prescribe hormone therapy (HT) to patients with symptoms of menopause because of concerns with CVD risk,” Leslie Cho, MD, director of the Cleveland Clinic’s Women’s Cardiovascular Center, told Healio. “There is confusion around the evidence-based guidelines that support hormone use. We thought this was a perfect time to address this issue, as there has been this enormous resurgence of interest in menopausal hormone treatment and major consumer wellness organizations have entered the fray.”
At one time, menopausal HT was almost universally recommended, Cho and colleagues wrote in a review published in Circulation. With the publication of the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI) trial, both of which reported excess CV risk with HT, use of HT declined substantially, Cho said.
However, during the past 20 years, the relationship of CVD risk with timing of menopause, initiation of HT and route of HT delivery has been better understood. Four major North American medical societies — the American College of Obstetricians and Gynecologists, American Association of Clinical Endocrinology, the Endocrine Society, and the North American Menopause Society — now recommend HT in appropriate patients for the management of menopausal symptoms.
“No one recommends hormones for CVD prevention,” Cho said in an interview. “HT does not impact weight or lower heart disease risk. HT is recommended for bothersome menopausal symptoms.”
Ideal candidates for HT
The review, led by the American College of Cardiology Cardiovascular Disease in Women Committee, along with leading gynecologists, women’s health internists and endocrinologists, states that ideal candidates for menopausal HT are women who are younger than 60 years or within 10 years of menopause onset, who have a 10-year estimated ASCVD risk of less than 5% and do not have an increased risk for breast cancer or history of venous thromboembolism.
A more nuanced approach for HT is recommended for women at intermediate CVD risk, defined as women who have diabetes, who smoke, have hypertension, obesity, metabolic syndrome or an autoimmune disease, among other risk factors.
“The presence of CVD risk factors alone does not preclude the use of HT, but a patient’s worsening cardiovascular risk profile around the menopause transition emphasizes the need to optimize primary prevention efforts, including lifestyle and pharmacological management,” the researchers wrote.
“There are many HT formulations, including systemic hormones, transdermal estrogen and progesterone, vaginal estrogen,” Cho said. “The lowest risk is vaginal estrogen because it is not systemically absorbed. Transdermal HT seems to be associated with less of an increase in cholesterol and BP and less risk for development of clots.”
Guidance does not recommend the use of bioidentical hormones, which are not FDA-regulated, Cho said.
‘Be thoughtful’ about menopausal HT
For the WHI, researchers randomly assigned women aged 50 to 79 years without CVD continuous combined oral conjugated equine estrogen (CEE) with medroxyprogesterone acetate or placebo; women without a uterus were randomly assigned to CEE alone or placebo. The initial findings suggested that compared with placebo, risks for CHD, stroke and VTE, including pulmonary embolism, were increased with HT. Subsequent analyses of the WHI, which were age-stratified with longer cumulative follow-up (median duration, 13 years) supported a more nuanced approach to HT, Cho said.
“The WHI initially showed that HT increases risk. That trial included women of all ages, women older than 60 years, those more than 10 years after menopause,” Cho said. “That scared everyone. But what we have learned since then — almost 20 years later — is that starting HT for younger women, and being mindful of HT type and for the shortest duration possible for symptom relief is actually quite safe. The nuanced approach is an important message to convey.”
Cho said for women aged 50 years and older with one or more risk factor for CVD, shared decision-making is key.
“We want to be thoughtful about which hormones are prescribed, and risk for women who have a history of stroke or blood clots, who should never receive HT,” Cho said. “The biggest takeaway is it is important that cardiologists know that HT for low-risk women is very safe. For intermediate-risk women — women with one or more risk factors — think about transdermal formulations. Those at high risk are not candidates for HT. The other important thing is we have to respect patient wishes and what is important for them. Using a nuanced approach and adopting shared decision-making is really important,” Cho told Healio.
For more information:
Leslie Cho, MD, can be reached at chol@ccf.org.
Perspective
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This review is encouraging. There was a time in the 1990s when the beneficial role of estrogens in vascular health seemed clear and convincing. Then, data from HERS and the WHI suggested menopausal HT could be deleterious. Estrogens were vilified in any other form other than transvaginal or for women who began menopause early, age 45 years or younger. Patients experiencing bothersome symptoms would see a clinician only to be told, “Sorry, I don’t have anything to make you feel better.”
We now know that the role of estrogen is more nuanced. Data from WHI show that, if you wait until 10 years or more after menopause, HT can be deleterious, for reasons that are still not completely understood today. It is now clear that there is a benefit to sustaining the estrogen effect; however, there appears to be potential for deleterious activity in some people prescribed menopausal HT, so discrimination between low-, intermediate- and high-risk people is important. The 2018 ACC guidelines for the treatment of CVD notes that menopause is a CVD risk enhancer. Data now suggest estrogen deprivation may explain why.
I do not typically treat vasomotor symptoms, but such symptoms weigh in my decision making. Typically, HT decisions are made in conjunction with an OB/GYN. Menopausal symptoms can be perplexing and disruptive; quality of life suffers for the patient and their family. Professional societies including the North American Menopause Society, Endocrine Society and the American Association of Clinical Endocrinology have all endorsed HT for menopause symptoms when appropriate. What this review offers is a finessing of the way these medications should be delivered, noting clinicians should be selective in who is prescribed HT.
Clinical Professor, Department of Medicine, Leon H. Charney Division of Cardiology
NYU Langone Health
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