Menopausal hormone therapy (MHT) has been linked to an increased risk of breast cancer which can persist for more than a decade after usage stops.
For every 100 women using oestrogen plus daily progestogen MHT, two extra cases of breast cancer were identified between age 50-69, according to researchers from the University of Oxford in England.
After stopping use, some excess risk was found to persist for more than 10 years - with the size of the risk linked to the duration of previous use.
The researchers said that if the associations are causal, this means MHT use has already caused around one million breast cancers in western countries - one-twentieth of the total since 1990.
Speaking on RTÉ's Today with Miriam, Professor John Crown who works as a consultant oncologist at St Vincent's Hospital in Dublin that although the data collected in the research are not staggeringly different than what we knew before, "the quantity is a little more concerning".
What the study has shown, Mr Crown said, is that "any HRT vs. no HRT causes some increase in cancer risk", with the exception of those who only used HRT for less than a year where the higher risk seems to be very low or none at all.
The downside is, the professor explained, is that it is often oncologists who put patients into menopause, especially during breast cancer treatment.
"We quite commonly cause women to have a premature menopause," he said, adding that he "hates doing it".
However, he warned women against making a decision about HRT based on media coverage, and instead appealed to them to go and talk to their doctor.
"This has to be individualised", he said, adding that both risks and benefits have to be evaluated.
"It is not as simple as if you take HRT, you’ll get cancer or die from cancer, and if you don’t, you won’t," he said.
Comparing the current crisis around HRT to the one from years ago, Mr Crown said the difference was that back then there was a sense that the HRT-related risks were "outweighed by potential survival benefits in terms of decreased cardiovascular and heart disease".
Sadly, he added, "it turned out that those benefits were not there".
Explaining why some patients are still ready to take HRT despite the proven risk, Mr Crown explained that it makes you feel much better and has a huge impact on quality of life, which is crucial to some people.
But the cost for getting that is that there is some increase in breast cancer risk.
So for a woman who wants to do everything she can to reduce the risk of getting breast cancer, he continued, "she shouldn’t take HRT".
Asked if the study is "categorically saying that HRT can cause breast cancer" and is it more worrying than the study that existed before, Mr Crown said: "The answer is yes and yes".
If you take HRT, he continued, your risk of getting cancer is clearly higher, with the exception of those who had taken it for less than a year.
The global analysis used data from more than 100,000 women with breast cancer from 58 epidemiological studies worldwide.
The researchers found that all types of MHT, except topical vaginal oestrogens, were linked to an increased risk of breast cancer.
The risks were greater for users of oestrogen-progestagen hormone therapy than for oestrogen-only hormone therapy.
Women tend to begin MHT at around the time of the menopause, when ovarian function ceases, causing symptoms including hot flushes and discomfort.
There are about 12 million users in western countries - about six million in North America and six million in Europe.
Although regulatory bodies in Europe and the USA recommend MHT be used for the shortest time that is needed, some clinical guidelines recommended less restrictive prescribing.
About five years of use is now common.
Co-author Professor Valerie Beral from the Nuffield Department of Population Health, University of Oxford, 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."
She added: "Before all we knew was that the risk was increased when they used, the belief was that it went away when they stopped.
"The main finding is that we now know the long-term effects, that the risk persists for more than a decade after stopping."
The authors found that 108,647 women developed breast cancer at an average age of 65 - and almost half of these had used MHT.
For women in western countries who have never used MHT, 6.3 women in every 100 on average go on to develop breast cancer between 50 and 69.
This was for those who took the treatment for five years, starting at age 50.
The figure increased to around 8.3 women in every 100 for women who used oestrogen plus daily progestagen, and 7.7 women in every 100 for users of oestrogen plus intermittent progestagen.
Researchers also found that the risk was twice as great for women who used MHT for 10 years.
There was little excess risk after using any form of MHT for less than a year.
Professor Richard Peto, Professor of Medical Statistics and Epidemiology also of the Nuffield Department of Population Health, University of Oxford, said the findings suggest MHT is causing an increased risk of breast cancer.
He added: "Don't want to be alarming, but don't want to be reassuring either."
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene and Tropical Medicine (LSHTM), said: "These results should not be used to cause alarm among women, but there is no doubt that they should follow the advice given by the MHRA in the UK and the FDA in the US that MHT be used for the shortest time that it is needed.
"MHT does offer real benefits for menopausal symptoms, but its use beyond one year seems to confer a steadily increasing risk of breast cancer with increasing years of use.
"This is a 'tour de force' in what has been done and the way it has been done - the findings cannot be dismissed."
The Health Products Regulatory Authority has issued advice for women and for doctors prescribing HRT.
It says women who have previously used HRT should watch out for signs of breast abnormalities and seek medical attention if they notice any changes in their breasts.
The HPRA says doctors should continue to follow recommendations about breast cancer and other risks in the product information for HRT medicines.
It added that women who have any concerns about their HRT treatment should discuss them with their doctor or pharmacist.
The authority added that it would, in conjunction with the European Medicines Agency and other national medicines authorities, look further at the data from the study and will continue monitoring the benefits and risks of HRT medicines.
