title: Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992-2008.
abstract: We assessed whether different oral progestogens in hormone replacement therapy may differentially affect the risk of endometrial cancer, using data from the Etude Epidémiologique auprès de femmes de l'Education Nationale (E3N), a French cohort study (1992-2008). Hazard ratios and their confidence intervals were derived from Cox models. Among 65,630 postmenopausal women (mean follow-up: 10.8 years), 301 endometrial cancers occurred. Compared with never use, ever use of estrogen + micronized progesterone was associated with an increased risk of endometrial cancer (hazard ratio (HR) = 1.80, 95% confidence interval (CI): 1.38, 2.34) that was significantly more marked with longer duration of use (for ≤5 years, HR = 1.39 (95% CI: 0.99, 1.97); for >5 years, HR = 2.66 (95% CI: 1.87, 3.77)). Although use of estrogen + dydrogesterone was not associated overall with endometrial cancer risk (HR = 1.05, 95% CI: 0.76, 1.45), there was a significantly increased risk with long-term use compared with never use (for >5 years, HR = 1.69, 95% CI: 1.06, 2.70). Users of preparations containing other progesterone derivatives or a norsteroid derivative were not at significantly increased risk (HR = 0.79 (95% CI: 0.60, 1.05) and HR = 1.30 (95% CI: 0.85, 1.99), respectively). In conclusion, micronized progesterone and, to a lesser extent, dydrogesterone at the doses used in France may not be sufficient to prevent estrogen-induced endometrial cancers.
authors.forename: Agnès
authors.initials: A
authors.lastname: Fournier
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mesrine
authors.forename: Alice
authors.initials: A
authors.lastname: Vilier
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chabbert-Buffet
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000139:chemically induced* / Q000517:prevention & control; D004394:Dydrogesterone / Q000008:administration & dosage*; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000639:trends; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D064887:Observational Studies as Topic; D011372:Progestins / Q000008:administration & dosage*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
chemical_list: D004967:Estrogens; D011372:Progestins; D004394:Dydrogesterone
keywords: cohort studies; dydrogesterone; endometrial neoplasms; hormone replacement therapy; progesterone; progestins