An analysis of over 50 studies suggests an association between short-term use of hormone replacement therapy (HRT) during menopause and a 40 percent increased risk of developing ovarian cancer. 

The study, published Thursday in the journal The Lancet, reviewed data from 21,488 women who lived in North America, Europe and Australia. Researchers observed that women who used HRT for only a few years were more likely to develop the two most common types of ovarian cancer, compared to women who had never taken HRT. Those types are serous epithelial and endometrioid ovarian cancer. HRT use was not linked to an increased risk of the other two main types of ovarian cancer: mucinous and clear cell ovarian cancers.

HRT for menopause is meant to replace hormones that the body no longer makes after menopause. Doctors used to prescribe it as a standard treatment to relieve hot flashes and other menopause symptoms, according to the Mayo Clinic. A large clinical study later suggested one type of the treatment— the estrogen-progestin pill Prerempo— posed more risks than benefits, and doctors started to become less inclined to prescribe it as a result. Those risks included heart disease, stroke, blood clots and  breast cancer.

However, that decrease in use has now leveled off, according to a news release for the current study. About 6 million women in the United Kingdom and the United States use HRT today to relieve menopause symptoms, including hot flashes, night sweats and vaginal symptoms like dryness, itchiness, burning and discomfort during sexual intercourse.

The new research analyzed use of the two most common types of HRT used during menopause: those containing only estrogen or those containing a combination of estrogen and progestagen.

Study author Sir Richard Peto, a medical statistics and epidemiology professor at the University of Oxford, said in the news release that his team’s research suggests that, among women who take HRT for five years starting at about age 50, there will be about one extra ovarian cancer diagnosis for every 1,000 users and one extra death from ovarian cancer for every 1,700 users.  

For the meta-analysis, over 100 scientists worldwide analyzed individual participant data from 52 studies— a body of research that they say encompassed all of the epidemiological evidence ever gathered on HRT use and ovarian cancer.

Study authors saw an increased risk of ovarian cancer among current users as well as those who had used the treatment within the past five years, but that risk declined over time after stopping treatment. But, among women who had used HRT for at least five years, that risk remained 10 years later.

"The definite risk of ovarian cancer even with less than five 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 U.K. and worldwide guidelines,” study author Dame Valerie Beral, epidemiology professor at the University of Oxford, said in the news release.

Researchers noted the increased risk was not altered by the age at which HRT began, body size, past use of oral contraceptives— which are thought to protect against ovarian cancer— hysterectomy, alcohol use, tobacco use, or family history of breast and ovarian cancer.

Current HRT guidelines from the World Health Organization (WHO) as well as those in the U.S. and Europe don’t mention ovarian cancer as a risk, the news release noted. The U.K. guidelines associate a risk with long-term use.