Research Highlights:
- A study of more than 100,000 women, ages 45 and older, taking oral estrogen hormone therapy for menopause, has found that estrogen ingested in pill form may be associated with an increased risk of high blood pressure compared to transdermal and vaginal estrogen.
- Oral estrogen was associated with a 14% higher risk of high blood pressure compared to transdermal estrogen creams and a 19% greater risk of high blood pressure compared to vaginal estrogen creams or suppositories.
- Non-oral estradiol (a specific form of estrogen) at the lowest dose and for the shortest period of time was associated with the lowest risk of developing high blood pressure.
Newswise — DALLAS, June 5, 2023 —Women aged 45 and above who consumed estrogen hormone therapy in tablet format exhibited a higher propensity for developing hypertension compared to individuals employing transdermal or vaginal applications, as per the latest study published in Hypertension, an American Heart Association journal subject to peer review.
The American Heart Association states that postmenopausal women experience reduced production of estrogen and progesterone in their bodies. These changes could potentially elevate the susceptibility to cardiovascular conditions, such as heart failure.
Prescribed for alleviating menopausal symptoms, gender-affirming care, and contraception, hormone therapy has been previously associated with potential reductions in cardiovascular disease risk among menopausal women under 60 years old or within 10 years of menopause. However, the impact of various hormone therapy types on blood pressure in menopausal women remains uncertain, as stated by the authors of this study. They highlighted that high blood pressure, a modifiable risk factor for cardiovascular disease, requires further investigation regarding its relation to different hormone therapy approaches.
Cindy Kalenga, the lead author of the study and an M.D./Ph.D. candidate at the University of Calgary in Alberta, Canada, explained, "We are aware that orally consumed estrogens undergo metabolism in the liver, which is linked to the elevation of factors that can contribute to heightened blood pressure."
Kalenga elaborated, stating, "We are aware that post-menopausal women face a heightened risk of developing high blood pressure compared to pre-menopausal women. Moreover, previous research has indicated that certain forms of hormone therapy are linked to increased rates of heart disease. To further explore the factors related to hormone therapy, including the method of administration (oral vs. non-oral) and the specific type of estrogen, we decided to delve deeper into their potential effects on blood pressure."
This study encompassed a substantial cohort of more than 112,000 women aged 45 years and above. These women were identified through health administrative data in Alberta, Canada, between 2008 and 2019 based on their fulfillment of at least two consecutive prescriptions for estrogen-only hormone therapy within a six-month cycle. The primary focus was to determine the occurrence of high blood pressure (hypertension), which was identified by analyzing health records.
Initially, the researchers examined the correlation between the method of administration for estrogen-only hormone therapy and the likelihood of developing high blood pressure after at least one year of commencing the treatment. They analyzed three different routes of hormone therapy administration: oral (taken by mouth), transdermal (applied to the skin), and vaginal application. Furthermore, the researchers assessed the specific formulation of estrogen employed and its association with the risk of developing high blood pressure. To conduct this study, the researchers scrutinized medical records of individuals undergoing estrogen-only hormone therapy. The two most prevalent forms of estrogen used by the participants were estradiol, which is a synthetic form closely resembling the natural estrogen produced in women's bodies during their premenopausal years, and conjugated equine estrogen, an estrogen therapy derived from animals and the oldest type of estrogen treatment.
The analysis yielded the following findings:
- Women who underwent oral estrogen therapy exhibited a 14% elevated risk of developing high blood pressure compared to those employing transdermal estrogen. Additionally, they had a 19% higher risk of developing high blood pressure compared to individuals using vaginal estrogen creams or suppositories. Notably, when considering age as a factor, a more pronounced association was observed among women below the age of 70 in comparison to those above 70.
- In comparison to estradiol, the use of conjugated equine estrogen was associated with an 8% increased risk of developing high blood pressure.
The authors of the study also observed that a longer duration of estrogen use and higher doses were linked to an increased risk of high blood pressure. Kalenga emphasized that the study's results imply that if menopausal women opt for hormone therapy, there are various types of estrogen available that may carry lower cardiovascular risks.
Kalenga further suggested that when considering hormone therapy for menopausal women, options such as low-dose, non-oral forms of estrogen (such as transdermal or vaginal estradiol) should be considered. It is recommended to use these forms for the shortest duration necessary, taking into account individual symptoms and weighing the risk-benefit ratio. Kalenga added that these forms of estrogen therapy may be associated with the lowest risk of developing hypertension. However, it is crucial to strike a balance between the potential benefits of hormone therapy, which includes alleviating common menopausal symptoms, and the associated risks.
On average, women worldwide experience natural menopause around the age of 50. According to the American Heart Association's 2020 Statement on Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention, current evidence suggests that initiating menopausal hormone therapy during the early stages of menopause may confer cardiovascular benefits. However, these benefits may not be as apparent during the later stages of menopause. Previous studies have indicated that menopausal hormone therapy can be beneficial in alleviating symptoms associated with menopause, such as hot flashes, night sweats, mood changes, and sleep disturbances.
Sofia B. Ahmed, one of the study's co-authors and a professor of medicine at the University of Calgary, Alberta, Canada, emphasized the global significance of menopause, stating that over a quarter of the world's female population is currently over the age of 50. Furthermore, it is projected that by 2025, there will be approximately one billion individuals experiencing menopause worldwide. Ahmed highlighted that around 80% of individuals going through menopause experience symptoms, which can persist for up to seven years. While menopause is a natural aspect of the aging process, it has wide-ranging implications for quality of life, economic impact, work productivity, and social relationships. Ahmed stressed the importance of providing individuals with the necessary information to make informed decisions regarding the most effective and safe hormonal treatments for managing menopause.
The study had several limitations that should be acknowledged. Firstly, the assessment of the impact of different forms of hormone therapy on high blood pressure outcomes was solely reliant on information obtained from medical records, which may not capture all relevant data. Moreover, the study did not include women below the age of 45 and did not collect specific data regarding hysterectomies or menopausal status. However, the initiation of estrogen therapy in women aged 45 and above was utilized as an indicator of postmenopausal status. It is important to note that the study focused on estrogen-only therapy, which is commonly prescribed for women who have undergone a hysterectomy, while women with an intact uterus may receive a combination of estrogen and progestin. Consequently, these findings may primarily apply to women undergoing estrogen-only hormone therapy, as noted by the authors. Furthermore, the study's findings cannot definitively extend to other populations that might potentially benefit from estrogen hormone therapy, including women with an intact uterus or those experiencing premature or early menopause.
The research study specifically examined women in Canada, and it is important to acknowledge that regional differences may exist. However, it is noteworthy that the current guidelines in Canada are generally aligned with the guidelines from the American College of Obstetricians and Gynecologists in the United States. Both sets of guidelines recommend the use of hormone therapy in women who have appropriate indications, while emphasizing that hormone therapy should not be considered as a means of preventing or treating hypertension or heart disease. These guidelines reflect the cautious approach and recognize the limitations and potential risks associated with hormone therapy in relation to cardiovascular health.
The authors of the study have expressed their intention to carry out further research in the field. Specifically, they plan to investigate the effects of combined estrogen and progestin therapy, as well as progestin-only formulations of hormone therapy, on heart and kidney diseases. By conducting these additional studies, the authors aim to gain a better understanding of the potential impacts and risks associated with different types of hormone therapy on cardiovascular and renal health.
Ahmed stressed the significance of acquiring comprehensive knowledge regarding safe and effective hormonal treatments for women experiencing menopause. She emphasized that ultimately, the decision regarding the most suitable approach should be individualized and involve open communication with healthcare professionals. Ahmed further emphasized the need for large-scale, randomized studies that take into account the multifaceted aspects of hormone therapy during this critical phase of the female lifecycle. By conducting such studies, researchers can gather robust evidence to inform medical practices and provide better guidance for women navigating menopause.
Co-authors are Amy Metcalfe, Ph.D.; Magali Robert, M.D., M.Sc.; Kara Nerenberg, M.D., M.Sc.; and Jennifer MacRae, M.D., M.Sc. Authors’ disclosures are listed in the manuscript.
The study was funded by the Canadian Institutes of Health Research.
Statements and conclusions of studies published in the American Heart Association’s scientific journals are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here.
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