The risk of gynecological cancers associated with different HRT formulations.: A nested case-control study in the German Cohort Study on Women's Health -: Gynecological tumors and HRT use

Background: Previous epidemiological studies have inconsistently shown an increased or decreased risk of cancer of the breast, ovary, and uterine corpus ill users of HRT. Limited information is available about different formulations - particularly concerning different progestins. Methods: A nested case-control study within the German Cohort Study on Women's Health was analyzed concerning the risk of gynecological malignancies in HRT users as opposed to never users. Logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to compare the risk of different estrogens and progestins in different formulations. Results: 427 cases of breast cancer, 69 of uterine corpus cancer, and 35 of ovarian cancer were identified in the cohort and compared with 1614, 263, and 135 controls for breast, uterine corpus, and ovarian cancer, respectively. The adjusted overall risk estimates for breast, uterine corpus, and ovarian cancer were 1.0 (0.8-1.3), 0.6 (0.2-1.5), and 0.2 (0.04-0.8) for breast, uterine corpus, and ovarian cancer, respectively. No clear trend of increasing risk with increasing lag-time between exposure and tumor diagnosis was observed. No clear time trends for the risk of gynecological cancer were observed with respect to duration of use, time since first HRT use, or time since last use. No obvious differences in the risk of gynecological cancer were found for the different HRT formulations; the numbers in the subgroups for uterine corpus and ovarian cancer, however, were too small to draw final conclusions. Conclusion: Ever-use of hormone replacement therapy is associated with risk estimates very close to unity (1.0-1.1). HRT use appears not to be associated with an increased risk of uterine corpus or ovarian cancer. In addition, no significant cancer risk trend was observed for duration of use or for time since first or last use. Different HRT formulations (composition and regimen) appear not to be associated with different cancer risks. These results need confirmation in a larger, sufficiently powered, case-control study.