Risk of Hypertension in Postmenopausal Women Higher with Oral Estrogen-only Hormone Therapy

Women aged ≥45 years who took oral estrogen hormone therapy (HT) to reduce symptoms of menopause were more likely to develop hypertension than those using either transdermal or vaginal formulations, according to results of a study by investigators from the Cumming School of Medicine at the University of Calgary, in Alberta.¹

Specifically, in a cohort of more than 110 000 postmenopausal women the research team found that the risk of developing hypertension was 14% higher among women taking oral estrogen HT compared to those using transdermal estrogen and 19% higher compared to women using vaginal estrogen creams or suppositories. Further, in models adjusted for participant age, the association with hypertension was stronger among those aged ≤70 years than those older than age 70. Investigators also reported that use of conjugated equine estrogen was associated with a slightly greater risk for hypertension compared to estradiol.¹

“We know estrogens ingested orally are metabolized through the liver, and this is associated with an increase in factors that can lead to higher blood pressure,” lead study author Cindy Kalenga, MD/PhD candidate at the University of Calgary in Alberta, Canada, said in a statement^.2

“We know that post-menopausal women have increased risk of high blood pressure when compared to pre-menopausal women; furthermore, previous studies have shown that specific types of hormone therapy have been associated with higher rates of heart disease,” Kalenga continued. “We chose to dive deeper into factors associated with hormone therapy, such as the route of administration (oral vs non-oral) and type of estrogen, and how they may affect blood pressure.”²

For the population-based study, Kalenga and colleagues identified women aged ≥45 years who filled ≥2 consecutive prescriptions for estrogen-only HT as recorded in linked provincial health administrative databases in Alberta between 2008 and 2019. Incident hypertension at least one year following initiation of treatment, identified via health records, was specified as the primary study outcome. Hazard ratios for hypertension in women using oral compared with transdermal, vaginal, or intramuscular HT were calculated using Cox proportional hazard models.

FINDINGS

The final cohort included 112 240 women who used an estrogen-only form of HT. Kalenga’s team reported a higher risk of incident hypertension in participants taking oral estrogen-only HT than with both transdermal (HR, 1.14; 95% CI, 1.08–1.20) and vaginal (HR, 1.19; 95% CI, 1.13–1.25) estrogens. When researchers analyzed the risk of hypertension by type of estrogen, they found an increased risk associated with conjugated equine when compared with estradiol (HR, 1.08; 95% CI, 1.04–1.14) but not when compared to estrone (HR, 1.00; 95% CI, 0.93–1.10). The researchers also reported in the study findings that both duration of estrogen exposure and cumulative dose of estrogen were associated with an increased risk of hypertension.

The level of cardiovascular risk posed by estrogens likely varies, observed Kalenga. “These may include low-dose, non-oral estrogen — like estradiol, in transdermal or vaginal forms — for the shortest possible time period, based on individual symptoms and the risk–benefit ratio,” she said.² “These may also be associated with the lowest risk of hypertension. Of course, this must be balanced with the important benefits of hormone therapy, which include treatment of common menopausal symptoms.”²

“Over a quarter of the world’s population of women are currently older than the age of 50. By 2025, it’s estimated that there will be one billion menopausal individuals on the planet,” study co-author Sofia B. Ahmed, MD, MMSc, professor of medicine at the University of Calgary, Alberta, Canada, said in the statement. “Approximately 80% of people going through menopause have symptoms, and for some it lasts up to seven years.²

“While menopause is a normal part of the aging process, it has huge implications for quality of life, economic impact, work productivity and social relationships. We need to give people the information they need to choose the most effective and safe hormonal treatments for menopause,” she added.²

References

1. Kalenga CZ, Metcalfe A, Robert M, et al. Association between route of administration and formulation of estrogen therapy and hypertension risk in postmenopausal women: a prospective population-based study. Hypertension. 2023;80:1463–1473. Published online June 5, 2023. doi:10.1161/HYPERTENSIONAHA.122.19938

2. Women taking oral estrogen hormones may have increased risk of high blood pressure. News release. American Heart Association. June 6, 2023. Accessed June 14, 2023.