Oxford, UK—Hormone replacement therapy used in conjunction with menopause increases risk of breast cancer and the extra risk can persist for a decade, even after the treatment is discontinued, according to an international collaboration that analyzed data from more than 100,000 women with breast cancer from 58 epidemiological studies worldwide.

The report, published in The Lancet, said heightened breast-cancer risk is associated with all types of menopausal hormone therapy other than topical vaginal estrogens. It further advises that risks are greater for users of estrogen-progestagen hormone therapy than for estrogen-only hormone therapy; for estrogen-progestagen therapy, the risks were greater if the progestagen was included daily rather than intermittently—e.g., for 10 to 14 days per month, according to the report.

How significant is the increased risk? Study authors suggested the following: For women of average weight in Western countries, 5 years of menopausal hormone therapy (MHT), starting at age 50 years, would increase breast-cancer incidence from ages 50 to 69 years by about one additional case in every 50 users of estrogen plus daily progestogen MHT, one in every 70 users of estrogen plus intermittent progestogen MHT, and one in every 200 users of estrogen-only MHT.

The meta-analysis used individual participant data from all eligible prospective studies, published between January 1, 1992, and January 1, 2018, that had sought information on the type and timing of MHT use.

During prospective follow-up, the authors point out that 108,647 postmenopausal women developed breast cancer at a mean age of 65 years (SD 7). Of those, 55,575 (51%) had used MHT.

“Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT,” the researchers explained.

In Western countries, MHT use, often initiated around the time of menopause, burgeoned during the 1990s, dropped to half in the early 2000s, and then reached a steady state during the 2010s, according to background information in the article. An estimated 12 million women in Western countries use menopausal hormone therapy, including about 6 million in North America, according to the article, which also points out that about 5 years of use is now common versus 10 years of use in the past.

“Use of menopausal hormone therapy for 10 years results in about twice the excess breast cancer risk associated with 5 years of use,” explained coauthor Gillian Reeves, MSc PhD, from the University of Oxford. “But, there appears to be little risk from use of menopausal hormone therapy for less than one year, or from topical use of vaginal estrogens that are applied locally as creams or pessaries and are not intended to reach the bloodstream.”

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