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Self-Reported Stress and Risk of Endometrial Cancer: A Prospective Cohort Study

From the National Institute of Public Health (N.R.N., K.S.-L., M.G.), Copenhagen, Denmark; Department of Epidemiology (N.R.N., Z.-F.Z.), UCLA School of Public Health, Los Angeles, California; National Institute of Occupational Health (T.S.K.), Copenhagen, Denmark; Copenhagen City Heart Study (P.S.), Epidemiological Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.

Address correspondence and reprint requests to Naja Rod Nielsen, National Institute of Public Health, Øster Farimagsgade 5A, 1399 Copenhagen K, Denmark. E-mail: nrn{at}niph.dk

Objectives: To assess a possible relationship between perceived stress and first-time incidence of primary endometrial cancer. Psychological stress may affect the synthesis and metabolism of estrogens and thereby be related to risk of endometrial cancer.

Methods: The 6760 women participating in the Copenhagen City Heart Study were asked about their stress level at baseline from 1981 to 1983. These women were prospectively followed up in the Danish nationwide cancer registry until 2000 and <0.1% were lost to follow-up. Cox proportional hazard models were used to analyze data.

Results: During follow-up, 72 women were diagnosed with endometrial cancer. For each increase in stress level on a 7-point stress scale, there was a lower risk of primary endometrial cancer (hazard ratio (HR) = 0.88; 95% confidence interval (CI), 0.76–1.01). This inverse association was particularly strong in women who received hormone therapy (HR = 0.77; 95% CI, 0.61–0.96) and in normal-weight women (HR = 0.73; 95% CI, 0.58–0.91).

Conclusions: Stress may affect gonadal synthesis of estrogens and alter the sensitivity of the uterus toward estrogen stimulation. These mechanisms may explain the lower risk of endometrial cancer observed among stressed women in this study. Despite these results, stress may still be a risk factor for a range of other diseases and should therefore not be considered a healthy response.

Key Words: psychological stress • endometrial neoplasms • prospective studies • estrogens

Abbreviations: HR = hazard ratio; CI = confidence interval; HPG = hypothalamic-pituitary-gonadal; HPA = hypothalamic-pituitary-adrenal; BMI = body mass index

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