title: Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix.
abstract: Digoxin is a phyto-estrogen capable of inducing hormonal effects. Use has been associated with increased risk of breast cancer, an estrogen-sensitive malignancy. The incidence of corpus uteri (uterus) cancer is also strongly increased with exposure to estrogens. Therefore, we evaluated whether digoxin use might also increase its incidence. In all women in Denmark, we identified digoxin users from 1995 through 2008 using a nationwide pharmacy registry system. Cancer occurrence was obtained from Danish Cancer Registry. Relative risk was determined using incidence risk ratios (RR) and 95% confidence intervals (CIs) relative to non-users after adjustment for age- and calendar-time. For ovarian and cervical cancers, RRs in users and non-users were similarly evaluated, these cancers representing gynecological cancers with weak or no associations to estrogen exposure. Of 2.1 million women, 104,648 (4.9%) had digoxin exposure and 137,493 6.5% had exposure to angina drugs but not digoxin during the study period. For uterus cancer, the RR was increased in current digoxin users (1.48, 95% CI: 1.32-1.65; N = 350). Incidence was marginally increased in former users. For ovary and cervix cancers, RRs in current digoxin users were 1.06 (95% CI: 0.92-1.22; N = 207) and 1.00 (95% CI: 0.79-1.25; N = 81), respectively. We examined risks in women using angina drugs but not digoxin to determine whether being under cardiac care affected risk. Among women using angina drugs only, RRs for uterus, ovary or cervix cancers were not statistically significant. We conclude that women currently using digoxin, a phyto-estrogen, have an increased risk of developing uterus cancers.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. rjbiggar@gmail.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Biggar
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000188:drug therapy; D003718:Denmark / Q000453:epidemiology; D004077:Digoxin / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology*; D048789:Phytoestrogens / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D048789:Phytoestrogens; D004077:Digoxin