Hormone therapy and the impact of estrogen intake on the risk of ovarian cancer

Background: The association between menopausal hormone therapy (HT) and risk of ovarian cancer is as yet equivocal, and the effect of estrogen and estrogenprogestogen therapy, specifically the effect of the cumulative hormone intake, is unclear. Methods: We conducted a nationwide population-based case-control study in Denmark. Cases were women aged 35 to 79 years with incident ovarian cancer diagnosed between January 1, 1995, and May 30, 1999. Controls were frequency age-matched women from the Danish Central Population Register. The analyses included data on 376 cases who have not undergone hysterectomy and 1111 controls. Results: The risk of ovarian cancer in relation to oral HT increased with the cumulative intake of the estrogen component of HT but not with the duration or the cumulative intake of the progestogen component when the 3 variables were mutually adjusted. A simple trend was found such that each additional gram of estrogen was associated with the same relative increase. The odds ratio was constant throughout the range of cumulative intake. After adjustment for established risk factors, the estimated odds ratio per each additional gram of cumulative estrogen was 1.056 (95% confidence interval, 1.003-1.112), corresponding to an odds ratio of 1.31 (95% confidence interval, 1.01-1.70) per 5 g of estrogen. Conclusions: Oral HT is associated with risk of ovarian cancer in women who have not undergone hysterectomy. Our results imply that the risk increases with cumulative oral estrogen intake but not with duration of HT, indicating that the increased ovarian cancer risk associated with oral HT may be diminished substantially by minimizing the daily dose of estrogen from oral HT.