Maturitas 53 (2006) 226–233 The association between early menopause and risk of ischaemic heart disease: Influence of Hormone Therapy  E. Løkkegaard a,d,* , Z. Jovanovic b , B.L. Heitmann c , N. Keiding b , B. Ottesen d , A.T. Pedersen d a The Danish Nurse Cohort Study, Center for Alcohol Research, National Institute of Public Health, Denmark b Department of Biostatistics, University of Copenhagen, Denmark c Research Unit for Dietary Studies and the Danish Epidemiology Science Center at Institute of Preventive Medicine, Copenhagen University Hospital, Denmark d The Juliane Marie Research Department, Copenhagen University Hospital, Rigshospitalet, Section 9431, Blegdamsvej 9, 2100 Copenhagen, Denmark Received 22 August 2004; received in revised form 5 April 2005; accepted 26 April 2005 Abstract Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether HT reduces this risk associated with early menopause. Objective: To analyse whether early menopause based on various causes are independent risk factors for ischaemic heart disease, and to investigate whether the risks are modified by use of HT. Methods: In a prospective cohort study questionnaires were mailed to Danish female nurses above 44 years of age in 1993. Information on menopause, use of HT and lifestyle was obtained. In total 19,898 (86%) nurses fulfilled the questionnaire, among them 10.533 were postmenopausal with definable menopausal age, free of previous ischaemic heart disease, stroke or cancer. Through individual linkage to national register incident cases of ischaemic heart disease were identified until end of 1998. Results: Menopause below both age 40 and 45 was associated with an increased risk of ischaemic heart disease, seeming most pronounced for women who had an early ovariectomy but also among spontaneous menopausal women. Generally HT did not reduce the risk except for the early-ovariectomised women, where no increased risk of ischaemic heart disease for HT users was found.  The study was approved by the scientific and ethical committees for Copenhagen and Frederiksberg (J.rt (KF) 01-103/93), the Danish Data Protection Agency was notified (1990-1110-270) and The Danish National Board of Health gave permission for access to The National Registry of Hospital Discharges and Death. The study was funded by grants 99-1-F-22720, 99-2-F-22775 and 01-1-9-F9-22882 from the Danish Heart Association. E. Løkkegaard was responsible for all parts of the research project including writing of the paper, Z. Jovanovic participated in statistical analyses and participated in writing the paper, N. Keiding supervised analyses, participated in interpretation and writing paper, B.L. Heitmann, B. Ottesen and A.T. Pedersen supervised the analyses, and took active part in writing the paper. * Corresponding author. Tel.: +45 35 45 73 69. E-mail address: loekkegaard@dadlnet.dk (E. Løkkegaard). 0378-5122/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2005.04.009