Short-term hormone replacement therapy related to increased risk of ovarian cancer

by Bruce Sylvester – Even just a few years of hormone replacement therapy (HRT) appears to significantly increase the risk of  two forms of ovarian cancer, researchers reported on Feb. 12, 2015 in The Lancet.

“For women who take HRT for 5 years from around age 50, there will be about one extra ovarian cancer for every 1000 users and one extra ovarian cancer death for every 1700 users,” said co-author Professor Sir Richard Peto from the University of Oxford in the UK.

As background, the investigators noted that HRT declined about a decade ago, but the decline has leveled off  in the UK and USA, where about 6 million women are still taking HRT. Notably,  WHO, US and European HRT guidelines do not cite a risk of ovarian cancer, and UK guidelines (in revision now) say that ovarian cancer risk might increase with long-term HRT.

The international Collaborative Group on Epidemiological Studies of Ovarian Cancer, centered at the University of Oxford, included more than 100 investigators worldwide. They analyzed data from 52 studies, representing almost all epidemiological data ever collected on HRT use and incidence of ensuing ovarian cancer. . Previous studies were not adequately powered with enough subjects to assess risks from only a few years of HRT use.

The analysis involved 21,488 subjects with ovarian cancer, mostly from North America, Europe and Australia.

They reported that subjects who used HRT for even a few years were approximately 40% more likely to develop ovarian cancer than non-users. They found significantly increased risk of ovarian cancer in those who had used HRT within the past 5 years.

Risk of ovarian cancer declined over time following treatment cessation. Subjects had used HRT for at least 5 years showed a non-significant  increased risk of ovarian cancer 10 years later after cessation.

HRT effects on risks of developing ovarian cancer were the same for the two main types of HRT, estrogen- only  or estrogen-plus-progestagen. Increase in risk was not significantly affected HRT-initiation age, body size, prior use of oral contraception, hysterectomy, alcohol use, tobacco use or family history of breast or ovarian cancer.

With four main types of ovarian cancer, the investigators found an increase in risk for the two most common types, serous cancer and endometrioid ovarian cancer, and not for mucinous cancer and clear cell ovarian cancer.

According to study co-author Professor Dame Valerie Beral, from the University of Oxford, “The definite risk of ovarian cancer even with less than 5 years of HRT is directly relevant to today’s patterns of use — with most women now taking HRT for only a few years — and has implications for current efforts to revise UK and worldwide guidelines.”

The study was funded by the Medical Research Council and Cancer Research UK.