Current, short-term use of hormone replacement therapy led to a 43% increase in risk of serous and endometrioid ovarian cancers, according to a large meta-analysis reported online in the Lancet.
Risk fell after women stopped hormone replacement therapy (HRT), but “remained appreciable” for the next few years, wrote the Collaborative Group on Epidemiological Studies of Ovarian Cancer. And long-term users had an estimated 25% increase in ovarian cancer risk, even a full decade after stopping HRT (relative risk, 1.25; 95% confidence interval, 1.07 to 1.46; P = .005), the group reported.
The findings “strongly suggest a causal relationship – i.e., that among otherwise similar women, use of hormone therapy increases the probability of developing the two most common types of ovarian cancer,” the group wrote (Lancet 2015 Feb. 13 [doi: 10.1016/ S0140-6736(14)61687-1]).
Guidelines on HRT from the United States and Europe do not mention ovarian cancer, and those from the United Kingdom describe only risk with long-term use. The findings are “directly relevant to medical advice, personal choices, and the current efforts to revise ... guidelines,” the investigators wrote.
The meta-analysis included 52 observational cohort studies, 17 of which were prospective. In all, 12,110 postmenopausal women in the prospective studies developed ovarian cancer, and 55% had used HRT. Women who had been on HRT for less than 5 years were 1.43 times more likely to develop ovarian cancer than were nonusers (RR, 1.43; 95% CI, 1.29 to 1.46; P < .0001). Thus, HRT might cause one extra case of ovarian cancer per 1,000 users, and one extra death from ovarian cancer per 1,700 users, the group wrote.
Risk of ovarian cancer was similar regardless of age and type of HRT use, the investigators said.
The Medical Research Council and Cancer Research UK funded the analysis. The authors declared no relevant financial conflicts of interest.