Women's breast cancer risk doubles if they use menopausal hormone therapy for 10 years rather than 5
For some women, menopause is a natural life transition, but for others, it means sleepless nights, hot flushes, and a decline in their overall health. And for decades, women have been prescribed synthetic versions of the hormones that are lost during menopause, to help mitigate the symptoms. However, women who use menopausal hormone therapy (MHT) are at a considerable risk of breast cancer, and some risk persists for over a decade after use stops, say researchers. According to analysis, increases in breast cancer risk is about twice as high for women who use the therapy for 10 years rather than 5 years.
Using data from 108,647 postmenopausal women, the researchers found that among the postmenopausal women who developed breast cancer by 65, 51% or 55,575 had used hormonal therapy.
Compared with never users, women who initiated MHT shortly after menopause had a significantly increased risk of invasive breast cancer, and the longer women used MHT, the greater the risk. While there was “little excess risk” after use of the hormonal therapy for less than one year, but there were definite excess risks associated with just 1–4 years of use, and progressively greater risks with longer use, shows analysis.
“The use of menopausal hormone therapy for 10 years results in about twice the excess breast cancer risk associated with 5 years of use. 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,” says co-author Professor Gillian Reeves from the University of Oxford, UK.
The findings, published in The Lancet, suggest that all types of MHT, except topical vaginal estrogens, are associated with increased risks of breast cancer. The 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, for example, for 10-14 days per month.
The researchers explain that estrogen-only menopausal hormone therapy is generally used by women who have had a hysterectomy (an operation to remove a woman’s uterus), while estrogen plus progestagen hormone therapy is usually used by women who have not had a hysterectomy. Progestagens are synthetic hormones that mimic the actions of natural progesterone.
What do past studies say?
Women tend to begin MHT at around the time of the menopause, when ovarian function ceases, causing estrogen levels to fall substantially, and progesterone levels drop to near zero. This causes some women to experience severe hot flushes and discomfort, which can be alleviated by MHT.
“MHT has been used mostly in western countries, with about 600 million woman-years of use since 1970. Use increased rapidly during the 1990s, halved abruptly in the early 2000s, and stabilized during the 2010s with about 12 million current users. Women tend to begin MHT around the time of the menopause and can continue for several years. At these ages, breast cancer is the most common malignancy in western countries; almost 3% of women are diagnosed with it during their 50s. While regulatory bodies in Europe and the USA recommend that MHT be used for the shortest time that it is needed, some clinical guidelines recommended less restrictive prescribing,” say the researchers.
A previous meta-analysis of the worldwide evidence had found that current and recent users of MHT were at an increased risk of breast cancer, but insufficient information was available about the effects of different types of MHT or about long-term risks after women had stopped using MHT.
What did the researchers find?
Accordingly, for the current study, the researchers brought together and re-analyzed all the eligible prospective studies centrally from 1992-2018 that had recorded MHT use. They also monitored breast cancer incidence, with 108,647 women subsequently developing breast cancer at an average age of 65 years. The team analyzed the type of MHT last used, duration of use, and time since last use in these women. The study was funded by Cancer Research UK and the Medical Research Council, and it was conducted by researchers from the Collaborative Group on Hormonal Factors in Breast Cancer.
The researchers found that 1 in 50 women taking the most common hormonal therapy for five years will get breast cancer. “For women of average weight in Western countries, five years of menopausal hormone therapy - which combined daily estrogen plus progestogen, starting at age 50 years - would increase breast cancer incidence from age 50 to 69 years by about one additional case in every 50 women,” says the study. Further, one in every 70 women of average height in Western countries, who used estrogen plus intermittent progestogen MHT for five years, and one in every 200 users of estrogen-only MHT for five years, would get breast cancer, shows analysis.
After stopping MHT, some excess risk persists for more than 10 years, but the size of this risk depended on the duration of previous use, say the researchers. If a woman had used MHT for less than a year, however, there was little excess risk thereafter. The findings show that for women of average weight in Western countries who have never used MHT, the average risk of developing breast cancer over the 20 years from ages 50 to 69 inclusive is about 6.3 per 100 women. This implies that about 63 in every 1,000 women who never use MHT, develop breast cancer during the 20 years, from ages 50 to 69.
“The increases in the 20-year risk include the increased risks both during the five years when MHT is being used and during the 15 years after use had stopped. The excess risks during and after MHT use depended on how long MHT had been used for. For MHT taken for five years, about half of the excess risk would be during the five years of current use, and the other half would be during the following 15 years after a woman stopped taking MHT. There was little excess risk after using any form of MHT for less than a year,” says the study.
Among women who developed breast cancer in the prospective studies, half had used MHT, the average age at menopause was 50 years, and the average age at starting MHT was also 50 years. The average duration of use of MHT use was 10 years in current users and seven years in past users.
The researchers say that as menopause usually occurs in women’s 40s and 50s, almost all the evidence was for women who had had their menopause and started MHT in this age range. The proportional increases in risk were similar for women starting MHT at ages 40-44, 45-49, 50-54, and 55-59. “The risks appeared, however, to be somewhat attenuated among the few who had started using MHT after age 60 years. The risks were also attenuated by adiposity, particularly for estrogen-only MHT, which had little effect in obese women,” says the study.
According to the research team, more data is needed as there is still not enough information on women who had used MHT for long periods and had stopped more than 15 years ago.
In a linked commentary, Dr. Joanne Kotsopoulos from the Women’s College Hospital, Canada, says that it is important to estimate the increased risks of breast cancer accurately from MHT. Clinicians must heed the message of this study but also take a rational and comprehensive approach to the management of menopausal symptoms, with careful consideration of the risks and benefits of initiating MHT for each woman. This might be dependent on the severity of the symptoms, contraindications for MHT (that is, breast cancer, cardiovascular disease, and stroke), and BMI, and could take into account patient preference. For likely candidates, MHT (preferably estrogen alone) should be initiated around the time of natural menopause and
ideally limited to 5 years of use,” she says.