Menopausal hormone therapy is associated with a twenty-two percent reduction in cardiovascular events among women with vasomotor symptoms, according to an analysis published in JAMA Internal Medicine. However, experts caution that the regimen should not be used specifically for heart disease prevention.
For decades, many women experiencing the physical disruption of hot flashes and night sweats have weighed relief against cardiovascular uncertainty. Now, a target trial emulation of observational data suggests that initiation of menopausal hormone therapy offers nuanced heart health implications that depend heavily on timing and patient demographics.
Timing, Demographics, and Cardiovascular Risk
The study, which examined perimenopausal and recently postmenopausal women with no prior history of cardiovascular disease, found that starting MHT reduced overall cardiovascular events by 22% (adjusted HR 0.78, 95% CI 0.62–0.98). The research was led by Samar El Khoudary, PhD, MPH, of the Virginia Commonwealth University School of Public Health in Richmond, along with co-authors.
When researchers looked closer at the window of intervention, the protective association sharpened for those who began treatment relatively early. Women who initiated MHT within 10 years of their menopause onset experienced an estimated 27% reduction in cardiovascular risk (aHR 0.73, 95% CI 0.58-0.93). Conversely, starting the therapy more than 10 years after menopause yielded no benefit (aHR 1.53, 95% CI 0.66-3.52), they wrote in JAMA Internal Medicine.
Demographic factors also revealed stark differences. The data indicated a protective effect specifically for Black women (aHR 0.51, 95% CI 0.33-0.81), while other races showed no clear cardiovascular benefit.
“given the lack of consistent CVD benefit and the overall risk-benefit balance, these findings should not be used to support the use of MHT for cardiovascular prevention.”
Study authors, via Medpagetoday
Weighing Symptom Relief Against Health Risks
Roughly 70% to 80% of women experience vasomotor symptoms, like hot flashes or night sweats, most often during perimenopause or menopause. Menopausal hormone therapy—also called postmenopausal hormone therapy and hormone replacement therapy—is sometimes used to replace the natural hormones estrogen and progesterone in a woman’s body during and after menopause, when levels of these hormones drop. Providers may recommend MHT to relieve common symptoms of menopause, such as hot flashes and vaginal dryness, and to address long-term biological changes, such as bone loss (osteoporosis), that result from declining levels of estrogen and progesterone.
MHT usually consists of estrogen alone or estrogen plus progestin, a synthetic form of progesterone. The hormones used in MHT are approved by the U.S. Food and Drug Administration (FDA) and come from a variety of plants and animals or are made in a laboratory, and their chemical structure is similar to those of hormones produced by women’s bodies.
The research observed an increased breast cancer risk among MHT initiators compared with non-initiators (aHR 1.41, 95% CI 1.00-1.98, P=0.02), while venous thromboembolism events showed no significant difference between the groups (aHR 1.00, 95% CI 0.39-2.58, P=0.99). These safety considerations echo decades of scrutiny that began with the pivotal Women’s Health Initiative (WHI) study, which for more than two decades cautioned that hormone therapy increased the risks of blood clots, strokes, and other health issues. However, recent regulatory actions have begun to shift how these therapies are labeled. Earlier this year, the FDA approved label changes for six hormone replacement therapies that removed boxed warnings for CVD, breast cancer, and probable dementia.
In an accompanying commentary, Regina Castaneda, MD, and Stephanie Faubion, MD, MBA, both of the Mayo Clinic in Jacksonville, Florida, wrote that the cardiovascular effects of MHT for those in the early stages of the menopause transition remain poorly characterized,
in part because the existing evidence is limited by the heterogeneity of hormone therapy preparations and routes of delivery used across studies.
Clinical Guidance and Future Outlook
In this study, the MHT used included systemic oral or transdermal estrogen with or without progestogens, including oral contraceptives. Castaneda and Faubion noted that this type of hormone exposure warrants discussion, given that the formulations used in contraceptives, characterized by higher estrogen doses and synthetic progestins, differ meaningfully from those used in postmenopausal hormone therapy regimens.
Notably, our study differs from the WHI because it includes younger women who initiated MHT during perimenopause or early postmenopause,
the study authors noted.
People should discuss the likely benefits and harms they might experience with their providers before deciding whether to use MHT and what form to use.
