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Discontinuation of postmenopausal hormone therapy elevates cardiac, stroke death risk
In the first year after discontinuation of postmenopausal hormone therapy, the risk for cardiac and stroke death increases, particularly among women aged younger than 60 years, according to findings published in Menopause.
“Associations between the long-term use of postmenopausal hormone therapy and risks of cardiovascular diseases have been studied for decades. The data are not uniform, perhaps partly due to differences in hormone therapy regimens and study populations,” Minttu M. Venetkoski, MD, from the department of obstetrics and gynecology at the University of Helsinki and Helsinki University Hospital, Finland, and colleagues wrote.
Venetkoski and colleagues studied the association between cardiac and stroke death risk and discontinuation of postmenopausal hormone therapy. The researchers used the National Medicine Reimbursement Register to identify 432,775 postmenopausal women from Finland who discontinued systematic hormone therapy between 1994 and 2013. They excluded women who had been diagnosed with cardiac or cerebrovascular events within 1 year prior to discontinuing hormone therapy.
The researchers identified the number of cardiac (n = 5,204) and stroke (n = 3,434) deaths and compared them with those in the age-matched Finnish background female population and those in the age-matched hormone therapy users.
Data showed that during the first year following treatment discontinuation, there was a significantly increased risk for cardiac death after 5 years or less of hormone therapy exposure (standardized mortality ratio [SMR] = 1.52; 95% CI, 1.13-2) and after more than 5 years of exposure (SMR = 2.08; 95% CI, 1.44-2.9) among women who discontinued hormone therapy at age younger than 60 years, compared with the age-matched female background population.
Similarly, there was a significantly increased risk for stroke death after 5 years or less of exposure (SMR = 2.62; 95% CI, 2.07-3.28) and after more than 5 years of exposure (SMR = 3.22; 95% CI, 2.29-4.4).
The elevated risk for cardiac and stroke deaths was greater when compared with hormone therapy users. When follow-up was conducted after 1 year, the increase in risk either disappeared or substantially declined, the researchers noted.
“Discontinuation of postmenopausal hormone therapy may be associated with increased risk of cardiac and stroke death during the first posttreatment year, particularly in women who discontinue hormone therapy before the age of 60 years,” Venetkoski and colleagues concluded.
They added, “The deaths reflect only a minor part of total burden of these diseases because for each woman who dies from cardiac cause or stroke, approximately five to 10 women will survive and continue living with different physical and mental incapacities. Further investigation is required to evaluate causality of the observed associations and to elaborate the possible biological mechanisms of hormone therapy termination-related cardiovascular risks.” – by Alaina Tedesco
Disclosure: Venetkoski reports no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.
Perspective
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The association between hormone therapy and CVD is complex. In the women’s health initiative, the use of conjugated equine estrogen with or without a synthetic progestin was associated with a reduction in cardiac events if initiated in women less than 60 years of age or within 10 years of menopause. However, an increased risk of CV events was seen for women aged older than 60 or 70 years, or more than 10 or 20 years from menopause.
The Finnish study found a significant elevated risk for cardiac and stroke death during the first year of discontinuation of hormone therapy, primarily for women younger than 60 years of age, with smaller risks seen in women who discontinued after age 60. The increased risk for CV deaths is theorized to be due to the loss of vasodilatory effects of estrogen, which leads to increased cardiovascular health risks. However, this epidemiologic study cannot provide cause and effect.
Limitations include a lack of information about CV risk profiles of the hormone therapy users, the reasons why hormone therapy was discontinued, and whether hormone therapy was abruptly stopped or tapered. There is no information of different types or routes of estrogens or progestogens therapies.
For women with an elevated risk for CVD or a family history of CVD or stroke considering hormone therapy, individual risk factors to take into account include family medical history (type, age, risk factors); personal history of elevated cholesterol, hypertension, diabetes or cigarette smoking; and lifestyle practices that affect risks.
Age and time from menopause when hormone therapy is initiated is important in determining potential benefits of hormone therapy, with early initiation of therapy appearing to have a positive impact on CV health. Findings from this study suggest that discontinuation of hormone therapy may be associated with increased cardiovascular risks, particularly for women aged younger than 60 and potentially for those at higher personal risk of CVD.