Breast cancer incidence, case-fatality and breast cancer mortality in Danish women using hormone replacement therapy--a prospective observational study.
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Biomedical subjects
Publications and source records attributed to Erik B Obel.
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Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow-up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT. In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56-6.75, and RR = 1.94, 95% CI = 1.26-3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.
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BACKGROUND: The authors compared self-reported non-spine fractures obtained from a cohort of Danish female nurses with fracture diagnoses registered in the Danish National Hospital Register (DNHR). METHOD: The self-reported fracture history was obtained from a questionnaire and was related to fracture information registered with the DNHR by means of the unique person identification code of Danish citizens. A total of 166 self-reported hip fractures, 391 self-reported wrist fractures, and 121 self-reported upper arm fractures were available for the comparison. The self-reported fractures were initially compared with the anatomic specific fracture diagnoses registered in the DNHR. Second, the comparison also included fracture diagnoses of adjacent skeletal sites (unspecific fracture diagnoses). RESULTS: The positive predictive value of a positive report of hip fracture was 89%. Inclusion of unspecific registered hip fractures increased the positive predictive value to 94%. The same figures for wrist fractures were 75% and 84%, respectively, and for upper arm fractures 54% and 83%, respectively. The predictive value of a negative report of hip fracture was 99.5%. The fracture year was correctly reported in 76% of the hip fracture cases, 81% of the wrist fracture cases, and 82% of the upper arm fracture cases. Predictors of false-positive report of fractures were young age ( < 60 years), report of indoor falls in the previous year, and use of hormone replacement therapy (HRT). CONCLUSION: The authors conclude that self-report of hip, wrist, or upper arm fractures among Danish nurses is relatively accurate but varies by the site of fracture. False positive reports of fracture introduce only modest bias fracture risk estimates and tend to dilute the association between exposures and fracture.
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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-17beta (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.
BACKGROUND: Studies have found that women who use hormone replacement therapy (HRT) are healthier or report better health than non-users. This study examines the association between lifestyle factors, self-reported health and the use of HRT in Danish female nurses above the age of 50 years. METHODS: Postal questionnaires were used for data collection. Two cohorts were examined, a younger including women between 50 and 59 years and an older including women of 60 years and above. RESULTS: Of the 14,071 nurses included, 5,528 (39%) reported ever using HRT. In both cohorts, ever using HRT was positively associated (odds ratio > 1) with intake of vitamin supplements, alcohol consumption at weekends, consulting a physician, use of medicine, and previous use of oral contraceptives. Only a few differences were found between former and current users of HRT. A highly significant association was found between ever using HRT and self-reported poor health. CONCLUSIONS: In this study use of HRT was not found to be associated with a particularly healthy lifestyle or better health. Therefore, these factors should be specifically considered in studies evaluating the effect of HRT.