Hormone replacement therapy (HRT) users have been told by the Medicines and Healthcare products Regulatory Agency (MHRA) to discuss its risks and benefits at their next routine GP appointment after a study* published in The Lancet today showed its use is linked to a persistent risk of breast cancer.
The study confirmed that women who use HRT for longer than one year have a higher risk of breast cancer than women who never use HRT. This known risk of breast cancer is well known and decreases once HRT is stopped. However, the study showed that some increased risk of breast cancer persists for more than 10 years compared to women who have never used HRT.
The increased risk of breast cancer occurs with all types of HRT, except for topical HRT applied directly onto or into the vagina. The risks are greater for users of oestrogen-progestagen hormone therapy than for oestrogen-only hormone therapy. For oestrogen-progestagen therapy, the risks were greater if the progestagen was included daily rather than intermittently (e.g. for 10-14 days per month).
Sarah Branch, deputy director of MHRA’s Vigilance and Risk Management of Medicines Division said: “Women should be aware of this new information, so that it can be considered with the other risks and benefits of using HRT.”
The menopause can have unpleasant side effects and HRT products can be effective in helping to ease the symptoms, but she emphasised: “No medicine is completely without risk, but it is important for women to be able to make an informed decision about the risks and benefits that are appropriate for them.”
The authors of The Lancet study brought together and re-analysed centrally all the eligible prospective studies from 1992-2018 that had recorded HRT use and then monitored breast cancer incidence, with 108,647 women subsequently developing breast cancer at an average age of 65 years.
Among women who developed breast cancer in the prospective studies, half had used HRT; the average age at menopause was 50 years, the average age at starting HRT was also 50 years, and the average duration of use of HRT use was 10 years in current users and seven years in past users.
For women of average weight in Western countries who have never used HRT, the average risk of developing breast cancer over the 20 years from ages 50 to 69 inclusive was about 6.3 per 100 women.
The authors estimated that for women with five years use of the three main types of HRT, starting at age 50, the 20-year breast cancer risks from ages 50 to 69 inclusive would increase from 6.3 per 100 in never-users to 8.3 per 100 in users of oestrogen plus daily progestogen, 7.7 per 100 in users of oestrogen plus intermittent progestogen, and 6.8 per 100 in users of oestrogen-only.
Co-author Professor Valerie Beral from the University of Oxford, UK, said: “Our new findings indicate that some increased risk persists even after stopping use of menopausal hormone therapy. Previous estimates of risks associated with use of menopausal hormone therapy are approximately doubled by the inclusion of the persistent risk after use of the hormones ceases.”
Co-author Professor Gillian Reeves from the University of Oxford, UK, said: “Use of menopausal hormone therapy for 10 years results in about twice the excess breast cancer risk associated with five 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 oestrogens that are applied locally as creams or pessaries and are not intended to reach the bloodstream.”
The proportional increases in risk were similar for women starting HRT in their 40s and 50s, but were somewhat attenuated among the few who had started using it after age 60 years. The risks were also attenuated by adiposity.
The MHRA advises that HRT should only be initiated for relief of menopausal symptoms that adversely affect quality of life. Women should use the lowest effective dose of HRT for the shortest duration and HRT should only be continued as long as the benefit in alleviating menopausal symptoms outweighs the risks associated with treatment.
*Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. The Lancet. Published: August 29, 2019. DOI: 10.1016/S0140-6736(19)31709-X