Extreme concentrations of endogenous sex hormones, ischemic heart disease, and death in women.
OBJECTIVE
Sex hormones may be critical determinants of ischemic heart disease and death in women, but results from previous studies are conflicting. To clarify this, we tested the hypothesis that extreme plasma concentrations of endogenous estradiol and testosterone are associated with risk of ischemic heart disease and death in women.


APPROACH AND RESULTS
In a nested prospective cohort study, we measured plasma estradiol in 4600 and total testosterone in 4716 women not receiving oral contraceptives or hormonal replacement therapy from the 1981 to 1983 examination of the Copenhagen City Heart Study. During ≤30 years of follow-up, 1013 women developed ischemic heart disease and 2716 died. In women with a plasma estradiol below the fifth percentile compared with between the 10th and 89th percentiles, multifactorially adjusted risk of ischemic heart disease was 44% (95% confidence interval, 14%-81%) higher; however, plasma estradiol concentrations did not associate with death. Also, in women with a plasma testosterone concentration at or above the 95th percentile compared with between the 10th and 89th percentiles, multifactorially adjusted risk was 68% (34%-210%) higher for ischemic heart disease, 36% (18%-58%) higher for any death, and 38% (15%-65%) higher for death from other causes than cardiovascular disease and cancer. These results were similar for postmenopausal women alone.


CONCLUSIONS
In women, extreme low concentrations of endogenous estradiol were associated with high risk of ischemic heart disease, and extreme high concentrations of endogenous testosterone were associated with high risk of ischemic heart disease and death.
['Benn|Marianne|M|', 'Voss|Sidsel Skou|SS|', 'Holmegard|Haya N|HN|', 'Jensen|Gorm B|GB|', 'Tybjærg-Hansen|Anne|A|', 'Nordestgaard|Børge G|BG|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D015415:Biomarkers D002423:Cause of Death D003718:Denmark D015536:Down-Regulation D004958:Estradiol D005260:Female D006801:Humans D008875:Middle Aged D017202:Myocardial Ischemia D011379:Prognosis D016016:Proportional Hazards Models D011446:Prospective Studies D018570:Risk Assessment D012307:Risk Factors D013739:Testosterone D013997:Time Factors D015854:Up-Regulation D055815:Young Adult
death testosterone epidemiology estrogens general social development and population gonadal steroid hormones myocardial infarction myocardial ischemia