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Analyses Based on the Danish Nurse Study

Ellen Løkkegaard, MD, PhD; Zorana Jovanovic, MSc; Berit L. Heitmann, PhD; Niels Keiding, MSc; Bent Ottesen, DrMedSci; Yrsa Andersen Hundrup, MN, PhD; Erik B. Obel, DrMedSci; Annette Tønnes Pedersen, MD, PhD

Arch Neurol. 2003;60:1379-1384.

Background  Recent randomized clinical trials suggest an increased risk of stroke with hormone therapy (HT), whereas observational studies have suggested mixed results. Differences in design, definitions of HT exposure, and stroke outcome may explain these discrepancies. Little attention has been paid to identifying subgroups of women who are particularly sensitive to HT.

Objectives  To investigate the risk of various stroke outcomes among women using HT based primarily on estradiol-17 (unopposed or combined with norethisterone acetate) and to assess the potential modifying effect by presence of risk factors for stroke.

Design  Prospective cohort study.

Setting  In 1993, the Danish Nurse Study was established, and questionnaires on lifestyle and HT use were sent to all Danish nurses older than 44 years, of whom 19 898 (85.8%) replied.

Participants  Postmenopausal women (n = 13 122) free of previous major cardiovascular and cerebrovascular disease and cancer.

Main Outcome Measure  Ischemic or hemorrhagic stroke (n = 144) identified in the national registries of hospital discharges and cause of deaths in the total follow-up through December 31, 1998.

Results  In 1993, 28.0% of the 13 122 were current HT users, 14.3% were past users, and 57.7% were never users. Overall, HT exposure was not consistently associated with stroke. However, subdivision based on the presence of hypertension showed a significantly increased risk of stroke among hypertensive women. Compared with hypertensive never HT users, an increased risk of total stroke was found with current use (hazard ratio, 2.35; 95% confidence interval, 1.16-4.74) and especially with current use of estrogen-progestin (hazard ratio, 3.00; 95% confidence interval, 1.33-6.76). Normotensive women had no increased risk of stroke with HT.

Conclusions  We found an increased risk of stroke among hypertensive but not normotensive women using HT. The present study suggests that HT should be avoided in hypertensive women.

From the Department of Obstetrics and Gynecology, Hvidovre Hospital (Drs Løkkegaard and Pedersen), Juliane Marie Centre, Rigshospitalet (Dr Ottesen), and Department of Biostatistics (Ms Jovanovic and Mr Keiding), University of Copenhagen; Research Unit for Dietary Studies and Danish Epidemiology Science Center, Institute of Preventive Medicine, Copenhagen University Hospital (Dr Heitmann); and Danish Nurse Study, National Institute of Public Health (Drs Hundrup and Obel), Copenhagen, Denmark. Dr Løkkegaard is now with the Centre for Alcohol Research, National Institute of Public Health, Copenhagen.

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