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Increased cardiac and stroke death risk in the first year after discontinuation of postmenopausal hormone therapy

Venetkoski, Minttu MD1; Savolainen-Peltonen, Hanna MD, PhD1,2; Rahkola-Soisalo, Päivi MD, PhD1; Hoti, Fabian MSc3; Vattulainen, Pia MSc3; Gissler, Mika PhD4,5; Ylikorkala, Olavi MD, PhD1; Mikkola, Tomi S. MD, PhD1,2

doi: 10.1097/GME.0000000000001023
Original Articles

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.

1University of Helsinki and Helsinki University Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland

2Folkhälsan Research Center, Biomedicum, Helsinki, Finland

3EPID Research Oy, Espoo, Finland

4National Institute for Health and Welfare, Helsinki, Finland

5Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Division of Family Medicine, Stockholm, Sweden.

Address correspondence to: Tomi S. Mikkola, MD, PhD, Helsinki University Hospital, Department of Obstetrics and Gynaecology, Haartmaninkatu 2, PO Box 140, FIN-00029 HUS, Helsinki, Finland. E-mail:

Received 6 July, 2017

Revised 2 October, 2017

Accepted 2 October, 2017

Funding/support: This work was supported by grants from the Päivikki and Sakari Sohlberg Foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, Finska Läkaresällskapet, the Orion Farmos Research Foundation, the Paavo Nurmi Foundation, Jane and Aatos Erkko Foundation and a Finnish governmental grant for research on health sciences.

Financial disclosure/conflicts of interest: TSM has been a speaker and/or received consulting fees from Mylan and Novo Nordisk. HS-P has been a speaker for Mylan and received funding for congress trips from Mylan, Finox Biotech, and MSD. PR-S has received funding for congress trips from Johnson & Johnson and Olympus. PV and FH work for EPID Research. EPID Research is a company that performs financially supported studies to several pharmaceutical companies. Other authors report no conflicts of interest.

© 2018 by The North American Menopause Society.