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Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality

Mikkola, Tomi S. MD, PhD1,2; Tuomikoski, Pauliina MD, PhD1; Lyytinen, Heli MD, PhD1; Korhonen, Pasi PhD3; Hoti, Fabian PhD3; Vattulainen, Pia MSc3; Gissler, Mika MSocSci, PhD4,5; Ylikorkala, Olavi MD, PhD1

doi: 10.1097/GME.0000000000000450
Original Articles

Objective: Data on the health benefits and risks of postmenopausal hormone therapy (HT) are derived mainly from the use of conjugated equine estrogens. Estradiol-based regimens may have a different risk-benefit profile. We evaluated the risk of death caused by coronary heart disease (CHD), stroke, or any disease among users of estradiol-based HT regimens in a nationwide study in Finland.

Methods: A total of 489,105 women who used HT from 1994 to 2009 (3.3 million HT exposure years), as indicated in the nationwide reimbursement register and the national Cause of Death Register, were followed. A total of 28,734 HT users died during follow-up; among the deaths, 3,843 were caused by CHD and 2,464 were caused by stroke. Mortality risk in HT users with varying duration of exposure (≤1 y, >1 to 3 y, >3 to 5 y, >5 to 10 y, or >10 y) was compared with that in an age-matched background population.

Results: Risk of CHD death was significantly reduced by 18% to 54% in HT users and was positively related to HT exposure time. Risk of stroke death was also reduced by 18% to 39%, but this reduction was not clearly related to HT exposure time. Risk of all-cause mortality was reduced in HT users by 12% to 38%, almost in linear relationship with duration of exposure. All these risk reductions were comparable in women initiating HT before age 60 years and women initiating HT at age 60 years or older.

Conclusions: In absolute terms, the risk reductions mean 19 fewer CHD deaths and 7 fewer stroke deaths per 1,000 women using any HT for at least 10 years.

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

2Folkhälsan Research Center, Helsinki, Finland

3EPID Research Oy, Espoo, Finland

4National Institute for Health and Welfare, Helsinki, Finland

5Nordic School of Public Health, Gothenburg, Sweden.

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

Received 21 December, 2014

Revised 21 January, 2015

Accepted 21 January, 2015

Funding sources had no role in study design, data handling, or manuscript preparation.

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

Financial disclosure/conflicts of interest: P.T., H.L., M.G., O.Y., and T.S.M. declare no competing interests. P.K., F.H., and P.V. work for EPID Research, a company that conducts financially supported studies for several pharmaceutical companies.

© 2015 by The North American Menopause Society.