No other prescription medication has generated such diverse opinions and created more confusion than hormone replacement therapy (HRT).
While there is little doubt that HRT will alleviate menopausal symptoms and improve quality of life, commencing the therapy can be a difficult decision for a woman and her doctor, given ongoing debate, particularly regarding a possible link between HRT and breast cancer.
The menopause, defined as an absence of periods for one year, is a natural phenomenon that occurs in all women. The average age of the menopause in Ireland is 51. Menopausal symptoms, which can develop before or after the cessation of menstruation, include night sweats, hot flushes, insomnia, muscle aches, anxiety and vaginal dryness. These affect at least 80 per cent of women, with a quarter experiencing severe symptoms. Fifty per cent of women will have symptoms that last at least seven years; however, only a small proportion will elect to take hormone replacement therapy.
The cause of menopausal symptoms is a reduction in circulating oestrogen levels as a result of the depletion of a women’s finite number of ovarian follicles. For the last 60 years, oestrogen replacement therapy in various forms has been advocated to address menopausal symptoms and prevent onset of certain diseases attributed to altered tissue sensitivity to decreased oestrogen levels.
Aggressive marketing
Between 1960 and 1975, prescribing levels for oestrogen replacement therapy almost doubled due to aggressive marketing by drugs companies and a popular belief that oestrogen replacement could prevent many diseases associated with ageing and made women feel younger and happier. However a number of studies in the mid-1970s demonstrated that oestrogen-only replacement therapy significantly increased the risk of endometrial cancer. This led to a sharp reduction in its use for a decade before combined hormone replacement therapy – using oestrogen and progesterone – was shown to be safe in women who still had a womb.
As a result, there are now essentially two forms of HRT: oestrogen-only compounds, which can be used safely in women who have had a hysterectomy, and combined oestrogen and progesterone HRT, which is indicated in women who still have a womb. There are many different combinations of drug and forms of delivery including patches and tablets.
The second major controversy to strike HRT was in 2003 when a large US study, the Women's Health Initiative, demonstrated that, contrary to popular opinion, the therapy did not protect against heart disease but increased the risk of stroke, blood clotting and breast cancer in patients taking combined HRT. These risks increased with prolonged use of the therapy particularly in women over 60 years of age. There was no increased risk of breast cancer seen in patients on oestrogen-only HRT; however these findings led to a sharp decline in HRT use over the following number of years.
The recent breast cancer findings were confirmed in the Million Women Study based in the UK; however the magnitude of the risk of breast cancer has stimulated extensive debate. Based on multiple additional studies and analyses, it is felt that if 1,000 women started taking HRT at the age of 50 between one and two additional women would develop breast cancer compared to the overall population risk. Cancer Research UK estimates that this risk is similar to that of being overweight or drinking 2-3 units of alcohol a day. A recent study in the UK has suggested that this risk may be underestimated by approximately 53 per cent, but even if this is the case the absolute numbers remain small.
It is understandable for women to be worried and confused about HRT given the various findings over many years. The best advice is that women who have a personal history of breast cancer should not take the therapy; however those at increased risk of developing breast cancer based on a strong family history may consider it if they are particularly symptomatic and alternative non-hormonal approaches have failed.
Recent studies of HRT in women who had their ovaries removed as they carried a BRCA mutation and were thus at increased risk of developing ovarian cancer, demonstrated that the risk of developing breast cancer was not significantly increased. However, given the mounting evidence linking combined HRT to breast cancer risk, these women may elect to also have their womb removed as part of their risk-reducing surgery so as they can take oestrogen-only HRT, which has never been associated with an increased breast cancer risk and may be protective.
What is clear from all the studies examining the relationship between breast cancer and HRT is that the risk is directly related to the length of time women take the therapy. Those who take it for more than 10 years are at significantly increased risk of developing breast cancer. Also when women stop taking HRT their risk returns to normal within five years; however it should be noted that patients often develop symptomatic relapse after stopping the therapy.
Benefits
It is important to say that in addition to the risks there are also significant benefits associated with HRT including treatment or prevention of osteoporosis, improved quality of life, possibly a reduction in colorectal cancer risk and obviously an improvement in menopausal symptoms, which should occur within three months.
Current guidelines suggest the decision to commence the therapy should be made on an individual basis. This should be done following a discussion of the risks, benefits and alternatives between women under 60 years of age and their doctor. The maximum duration of treatment should be five years. The notable exception to this is women who develop a premature menopause who should commence HRT until the age of 51. None of the studies described previously were related to these patients and they have significantly increased risk of developing osteoporosis.
Ongoing research into HRT may further clarify the risks outlined above; however symptomatic women considering HRT should do so based on their own individual risk profile in consultation with their doctor. All women on HRT should have an annual medical review.
Donal Brennan is professor of gynaecological oncology at UCD and a consultant obstetrician and gynaecological oncologist at the Mater hospital and the National Maternity Hospital in Dublin
