Abstract B101: Menopausal hormone therapy and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Abstract

Abstract Use of estrogen-only menopausal hormone therapy (HT) has been consistently associated with an increased risk of ovarian cancer, although uncertainty still exists about the association with other types of HT. We assessed the association of various types of HT use at baseline with risk of ovarian cancer among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition (EPIC), after excluding women with prevalent cancer at recruitment and women with bilateral ovariectomy. After an average of 9 years follow-up, 424 ovarian cancers were diagnosed. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models stratified by EPIC recruitment center and age at enrolment (≤50, 51-53, 54-56, 57-59, 60-62, 63-65, >65 years), and adjusted for body mass index (BMI; continuous), cigarette smoking (never, former, current), unilateral ovariectomy (yes, no), hysterectomy (yes, no), age at menarche (<12, 12, 13, 14, ≥15), number of full-term pregnancies (0, 1, 2, 3, ≥4), and duration of oral contraceptive use (never use, ever use: ≤1, 2-4, 5-9, ≥10 years). A total of 56,534 women (45%) had ever used HT and 37,630 (30%) were current users at recruitment. Among current users, 69% used estrogen plus progestin HT, 18% used estrogen-only HT, 3% used tibolone, 2% used other preparations and 8% had missing information on type of HT use. The risk of ovarian cancer increased with increasing duration of ever HT use (P-trend, 0.04), although only women with use of five or more years had a significantly increased risk relative to never users (HR, 1.45; 95% CI, 1.08 — 1.94). Compared to baseline never use, current use of any HT was positively associated with risk (HR, 1.29; 95% CI, 1.01 — 1.65). Current use of estrogen-only HT was associated with a higher risk of ovarian cancer (HR, 1.63; 95% CI, 1.08 — 2.47), but use of estrogen plus progestin HT was not significantly associated with risk (HR, 1.20; 95% CI, 0.89 — 1.62). Use of tibolone was associated with a two-fold greater risk of ovarian cancer (HR, 2.19; 95% CI, 1.06 — 4.50), but this association was based on only eight exposed cases. The association of HT use and ovarian cancer did not differ significantly according to specific hormonal constituents, regimens and routes of administration of HT, or by ovarian cancer histology, EPIC-participating country, and baseline characteristics (BMI, smoking, parity, and oral contraceptive use). When we repeated the analysis by imposing additional censorship on all participants at 4, 6, 8, and 10 years of follow-up, to evaluate the assumption that HT use reported at recruitment remained constant throughout the follow-up, the findings were very similar. Our results are compatible with an increased risk of ovarian cancer for HT use, especially for women using estrogen-only therapy. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B101.