Study Shows Menopausal Hormone Therapy Linked To Increased Risk Of Breast Cancer
An international research collaboration led by the University Of Oxford and involving Big Data analysis of over 100,000 female patients with breast cancer from 59 epidemiological studies worldwide, has found that using Menopausal Hormone Therapy (MHT) is associated with an increased risk of breast cancer and increased risk persists even for more than a 12 years after usage is stopped. The findings have been verified by other institutions involved in the study and has been published in the medical journal, The Lancet.
Results from the study show that all types of MHT, with the exception of topical vaginal oestrogens, are associated with increased risks of breast cancer cancer, and that the risks are even greater for users of oestrogen-progestagen hormone therapy compared to that involving the oestrogen-only protocol. For oestrogen-progestagen therapy, the risks were greater if the progestagen was included daily rather than intermittently.
Many females tend to begin MHT at around the time of the menopause, when ovarian function ceases, causing both hormones oestrogen progesterone levels to fall to near zero, and also creating symptoms like serious hot flushes and discomfort. Although EU and US regulatory bodies recommend MHT be used for the shortest time that is needed, some clinical guidelines recommended less restrictive prescribing.
In most countries, MHT use increased rapidly during the 1990s, halved abruptly in the early 2000s, then stabilised during the 2010s. Currently, there are about 12 million users in Western countries, about six million in North America and six million in Europe (including one million in the UK). In Asia the figure is about 21 million users! Although some are short-term users, about five years of use is now common, whereas about 10 years of use used to be common. A previous meta-analysis of the worldwide evidence 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 MHT use had ceased until now.
"The research 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."commented Co-author Professor Valerie Beral from the University of Oxford in an interview with Thailand Medical News.
In this new research, the team brought together and re-analysed centrally all the eligible prospective studies from 1992-2018 that had recorded MHT use and then monitored breast cancer incidence, with 108,647 female patients subsequently developing breast cancer at an average age of 60 years. They looked at the type of MHT last used, duration of use, and time since last use in these women.
Among female patients who developed breast cancer in the research study, 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 estimate that for women with five years use of the three main types of MHT, 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 progestagen (ie, 8
3 in every 1,000 users would develop breast cancer) - an absolute increase of 2 per 100 users (one in every 50 users);
- 7.7 per 100 in users of oestrogen plus intermittent progestagen (ie, 77 in every 1,000) - an absolute increase of 1.4 per 100 users (one in every 70 users);
- 6.8 per 100 in users of oestrogen-only (ie, 68 in every 1,000 users) - an absolute increase of 0.5 per 100 users (one in every 200 users).
Increases in breast cancer risk would be about twice as great for female patients who use MHT for 10 years rather than 5 years. 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.
Use of menopausal hormone therapy for 10 years results in about twice the excess breast cancer risk associated with 5 years of use. Overall, MHT use was much more strongly associated with oestrogen-receptor-positive (ER+) breast cancer than with other types of breast cancer (as hormonal factors mainly affect ER+ breast cancer). The increased risk of developing ER+ breast cancer accounted for most of the excess breast cancer risk associated with MHT.
Menopause usually occurs in females's 40s and 50s, almost all the evidence was for females who had had their menopause and started MHT in this age range. The proportional increases in risk were similar for females 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 oestrogen-only MHT, which had little effect in obese females)
Based on the results of this new study, Doctors and Health Professionals need to take a careful approach to the management of menopausal symptoms, with careful consideration of the risks and benefits of initiating MHT for each female patient. This might be dependent on severity of the symptoms, contraindications for MHT , patients history, and genetics and also take into account patient preference.
Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence, The Lancet