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Increased cardiac and stroke death risk in the first year after discontinuation of HT

Discontinuation of postmenopausal Hormone therapy (HT) may be associated with increased risk of cardiac and stroke death in the first post-treatment year.

Hormone therapy (HT) continues to be a hotly debated topic. The benefits of oestrogen to the heart, however, appear to be universally accepted.

Since publication of the Women's Health Initiative (WHI) clinical trial data, there has been significant disagreement over the various risks and benefits of HT. What remains relatively unchallenged is the fact that oestrogen has rapid beneficial vascular effects and that shorter periods between the onset of menopause and the initiation of HT provide greater protection against cardiovascular disease. This beneficial relationship between HT and protection against heart disease has led to the speculation that withdrawal from HT could result in clinically significant changes in arterial function.

Although previous studies have shown that termination of oestradiol-based HT led to significant increases in the risk of cardiac and stroke deaths, particularly during the first year, these results were questioned because women with documented heart problems had not been excluded from the study.

This study, however, involving more than 400,000 Finnish women excluded women with prior cardiac or stroke events. The results of the study showed that discontinuation of HT was associated with an increased risk of cardiac and stroke death during the first post-treatment year, especially in women who discontinued HT aged younger than 60 years. This increased risk was not observed in women aged 60 years or older at the time of discontinuation.

"Since the initial Women's Health Initiative reports, studies have shown that hormone therapy has many benefits and is safer than originally thought. This is especially true for symptomatic menopausal women younger than age 60 and within 10 years of menopause, as these women had fewer heart events and less risk of mortality," says Dr JoAnn Pinkerton, North American Menopause Society (NAMS) executive director. "This new study suggests that younger women may have a higher risk of heart disease and stroke during the first year of discontinuation. Thus, women and their healthcare providers need to consider the benefits and risks of starting and stopping hormone therapy before making any decisions."

Objective: The aim of the study was to evaluate the risk of cardiac and stroke deaths in women who discontinue postmenopausal hormone therapy (HT).
Methods: We analyzed the risk of death due to cardiac (n = 5,204) and cerebrovascular (n = 3,434) causes in Finnish women who discontinued systemic HT during 1994 to 2013 (n = 432,775). The risks were compared with those in the age-matched female background population and with those in age-matched HT users. Women diagnosed with cardiac or cerebrovascular events within 1 year before discontinuation of HT were excluded (n = 8,711).
Results: Women younger than 60 years at discontinuation of HT showed a significantly increased risk of cardiac death (after <=5 y of HT exposure, standardized mortality ratio [SMR] 1.52, 95% CI 1.13-2.00; after >5 y of exposure, SMR 2.08, 95% CI 1.44-2.90) and stroke death (after <=5 y of exposure, SMR 2.62, 95% CI 2.07-3.28; after >5 y of exposure, SMR 3.22, 95% CI 2.29-4.40) during the first year after treatment as compared with age-matched female background population. When compared with HT users, elevations in risks of cardiac and stroke deaths were even higher. Increased mortality risks were limited to the first post-HT year because increases in risks vanished or markedly decreased when the follow-up time was extended over more than 1 year.
Conclusions: Discontinuation of postmenopausal HT may be associated with increased risk of cardiac and stroke death in the first posttreatment year. Further investigation is required to evaluate causality of the observed associations.

Venetkoski, Minttu M; Savolainen-Peltonen, Hanna M; Rahkola-Soisalo, Päivi K; Hoti, Fabian; Vattulainen, Pia; Gissler, Mika VJ; Ylikorkala, Olavi; Mikkola, Tomi S

[link url=""]North American Menopause Society material[/link]
[link url=""]Menopause abstract[/link]

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