The number of women using hormone replacement therapy (HRT) in Western countries increased rapidly in the 1990s, and then, with the publication of the Women’s Health Initiative study in the early 2000s, dropped by more than half. HRT use leveled off during the 2010s, and currently about 12 million women in North America and Europe take hormones to reduce the effects of menopause. It is commonly used for about five years.

Some risk persisted even 10 years after women stopped taking HRT.

Hormone replacement therapy fell out of fashion when an analysis of large amounts of data showed that HRT increased breast cancer risk, even after women stopped taking it. However, little evidence was available about the effect of different types of HRT on breast cancer risk, or about long-term breast cancer risk after women stopped taking it.

In a new meta-analysis of 58 prospective studies, an international group of researchers found that taking all types of HRT, with the exception of topical vaginal estrogen, is associated with an increased risk of breast cancer. And some risk persisted even 10 years after women stopped taking HRT.

The researchers analyzed data from studies that recorded HRT use among participants and then followed the women to see if they developed breast cancer. The anonymous data included the type of hormone replacement therapy a woman took, the length of her HRT use and how long it had been since she had stopped taking HRT.

Telling Numbers

Among the women enrolled in these studies, 108,647 later developed breast cancer at an average age of 65; nearly 425,000 women without breast cancer served as controls. About half of the women who developed breast cancer had used HRT starting at around age 50. The women who were currently using HRT had been taking it for about 10 years, and the women who had taken HRT in the past and then stopped had taken it for about seven years.

Roughly 63 out of 1,000 women who never use HRT and are of average weight in Western countries will develop breast cancer between the ages of 50 and 69. The researchers estimated that the risk for users of daily estrogen and progesterone would increase by one in every 50 HRT users, one in every 70 users for users of daily estrogen and intermittent progesterone, and one in every 200 users of estrogen only. The increase in breast cancer risk persisted even after the women discontinued HRT use.

The increase in breast cancer risk was found to be twice as great for women who took HRT for 10 years compared to those who took it for five years.

“We shouldn’t take these findings lightly,” Joanne Kotsopoulos, the author of a related editorial published along with the study, told TheDoctor.

HRT may also lead to stroke or blood clots.

Every woman’s experience going through menopause is different, she explained, so it’s important for women who take HRT to make sure it relieves their symptoms. They should strive to keep the length of their HRT use to a minimum. “Knowing HRT is a risk factor for breast cancer, clinicians and patients must take a comprehensive approach to managing menopausal symptoms,” said Kotsopoulos, a scientist and Canada research chair at Women’s College Research Institute in Toronto.

Some women are good candidates for HRT, according to Kotsopoulos. For example, women who are genetically predisposed to breast and ovarian cancer are advised to have their ovaries removed at age 35 or 40. These women are strongly advised to initiate HRT around the time of menopause. “So there is a place for HRT,” she indicated.

Women should keep a log of their symptoms, advises Kotsopoulos. They should note how severe their symptoms are, when they happen and how often. They should also note how their symptoms have affected their quality of life.

HRT may also lead to stroke or blood clots, so women should discuss their history of stroke and cardiovascular disease with their provider. “These are things your clinician will take into account to determine if you are a candidate for HRT,” she added.

The study and related editorial are published in The Lancet.