Meta-Analysis Shows Increased Risk of Ovarian Cancer With Menopausal Hormone Therapy
In a study reported in The Lancet, the Collaborative Group on Epidemiological Studies of Ovarian Cancer found that use of menopausal hormone therapy was associated with an increased risk of ovarian cancer, with the risk being highest among current users.
The study consisted of meta-analyses of individual participant datasets from 52 epidemiologic studies, including 17 prospective and 35 retrospective studies. The principal analyses involved prospective studies, with last hormone therapy use extrapolated forward for up to 4 years.
Risk in Current and Past Users
During prospective follow-up in the principal analysis, 12,110 postmenopausal women developed ovarian cancer, including 6,601 (55%) who had used hormone therapy. Compared with never-users, current users had a similar significantly increased risk of ovarian cancer with < 5 years of use (relative risk [RR] = 1.43, P < .00001) and ≥ 5 years of use (RR = 1.41, P < .0001). Among past users with < 5 years since last use, the risk was significantly increased among those with ≥ 5 years of use (RR = 1.29, P = .0008) and nonsignificantly increased in those with < 5 years of use (RR = 1.17, P = .08). Among past users with ≥ 5 years since last use, the risk was significantly increased among those with ≥ 5 years of use (RR = 1.10, P = .02) but not among those with < 5 years of use (RR = 0.94, P = .1).
Risk With Current/Recent Use
Compared with nonuse, current or recent use, defined as use of any duration stopped < 5 years before diagnosis, was associated with a significantly increased risk (RR = 1.37, P < .0001). This risk was similar in European and American prospective studies and for estrogen-only and estrogen-progestogen hormone preparations. The risk differed across the four main tumor types (P < .0001 for heterogeneity), with significant risk being observed for serous tumors (RR = 1.53, P < .0001) and endometrioid tumors (RR = 1.42, P < .0001). Although risk declined with greater duration since last use, the risk of serous or endometrioid tumors was still significant at 10 years since last use (RR = 1.25, P = .005).
Sensitivity analysis including data from retrospective studies produced results similar to those in the principal analysis, with slightly reduced RRs.
The investigators concluded: “The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1,000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1,700 users.”
The study was funded by the Medical Research Council, Cancer Research UK. The study authors reported no potential conflicts of interest.
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