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.