CV risks vary based on menopausal hormone therapy combinations, administration methods
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Key takeaways:
- Oral estrogen-progestin use was tied to higher ischemic heart disease and venous thromboembolism risks.
- Tibolone use was tied to higher risks for cerebral and myocardial infarction and ischemic heart disease.
Cardiovascular disease risks vary depending on the type of menopausal hormone therapy combinations and administration methods used, according to a nationwide trial published in The BMJ.
“Experimental studies have shown that estrogen plays a protective role in cardiovascular health by promoting angiogenesis and vasodilation, reducing cardiac fibrosis and oxidative stress and increasing high density lipoprotein cholesterol concentrations,” Therese Johansson, MD, postdoctoral researcher in the department of immunology, genetics and pathology at SciLifeLab and the Centre for Women’s Mental Health during the Reproductive Lifespan (WOMHER) at Uppsala University, Sweden, and colleagues wrote. “More than 2 decades ago, observational studies conducted through the Nurses’ Health Study in the U.S. and the General Practice Research Database in the U.K. supported a potential cardiovascular benefit for postmenopausal women using HT. However, subsequent randomized trials, including the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women’s Health Initiative trial, showed the opposite.”
Johansson and colleagues conducted a nationwide register-based emulated target trial using data from 919,614 women aged 50 to 58 years living in Sweden between 2007 and 2020. All women had no history of HT use within the past 2 years. Researchers designed 138 nested trials occurring monthly from July 2007 to December 2018 and women not on HT were assigned to one of eight treatment groups including oral combined continuous, oral combined sequential, oral unopposed estrogen, oral estrogen with local progestin, tibolone, transdermal combined, transdermal unopposed estrogen or non-initiators of menopausal HT.
The primary outcomes included venous thromboembolism, ischemic heart disease, cerebral infarction and myocardial infarction separately and as composite CVD outcomes.
Overall, 77,512 women initiated menopausal HT. Overall, 24,089 women had a CV event recorded during follow-up, with 43% experiencing ischemic heart disease, 17% experiencing cerebral infarction, 17.9% experiencing MI and 38.2% experiencing VTE.
Compared with women not on menopausal HT, those using tibolone had an increased risk for CVD (HR = 1.52; 95% CI, 1.11-2.08). Women using tibolone (HR = 1.46; 95% CI, 1-2.14) or oral estrogen-progestin therapy (HR = 1.21; 95% CI, 1-1.46) had a higher risk for ischemic heart disease.
Women using oral continuous estrogen-progestin (HR = 1.61; 95% CI, 1.35-1.92), sequential therapy (HR = 2; 95% CI, 1.61-2.49) and estrogen-only therapy (HR = 1.57; 95% CI, 1.02-2.44) had a higher risk for VTE.
In addition, in per-protocol analyses, researchers observed an association between tibolone use and higher risk for cerebral infarction (HR = 1.97; 95% CI, 1.02-3.78) and MI (HR = 1.94; 95% CI, 1.01-3.73).
“The study did not extend to the effects of specific progestins within these therapy formulations. Bioidentical progesterone, compared with synthetic progesterone, has been suggested to confer different risk profiles regarding cardiovascular disease,” the researchers wrote. “Hence, future research should investigate the potential various effects on the risk of cardiovascular disease based on different progestogens used in menopausal hormone therapy.”
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